Presynaptic muscarinic receptors: Change of sensitivity during long-term drug treatment

International Nuclear Information System (INIS)

Marchi, M.; Raiteri, M.

1986-01-01

The authors investigate some of the characteristics of auto- and heteroreceptors from different brain areas in male rats; their alteration in sensitivity following chronic drug treatment is monitored. The synaptosomes were prelabeled with tritium-choline or tritium-dopamine and the release of tritium-acetylcholine and tritium-DA was studied in superfusion. It is shown that the difference in susceptibility between auto- and heteroreceptors with respect to changes of sensitivity may represent a further criterion to discriminate between muscarinic receptor subtypes

Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

International Nuclear Information System (INIS)

Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P.

1991-01-01

The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 [11-2-[[2-[diethylaminomethyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one], hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of [3H]quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of [3H]-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated

Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

International Nuclear Information System (INIS)

Sanborn, B.B.; Schneider, A.S.

1990-01-01

Inositol trisphosphate (IP 3 ), a product of the phosphoinositide cycle, mobilizes intracellular Ca 2+ in many cell types. New evidence suggests that inositol tetrakisphosphate (IP 4 ), an IP 3 derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP 4 are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP 4 in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine stimulated an increase in [ 3 H]IP 4 and [ 3 H]IP 3 accumulation in chromaffin cells and this effect was completely blocked by atropine. [ 3 H]IP 4 accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP 3 and IP 4 hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP 4 and calcium homeostasis

Changes of muscarinic cholinergic receptors during aging process of primary cultured neutrons

International Nuclear Information System (INIS)

Fan Guohuang; Yi Ningyu; Xia Zongqin

1996-01-01

The dynamic changes of muscarinic receptor density and its reactivity during aging process in primary cultured neutrons were studied. Muscarinic receptor density was measured by 3 H-QNB binding assay, and muscarinic receptor reactivity was assessed by carbachol stimulation of cGMP formation, the latter was measured by RIA. After 2 weeks' incubation of neonatal rat brain cells, the nutrients began to rupture and the cell bodies shrank markedly showing senescent feature. The muscarinic receptor density reached peak at the 12th day in vitro (12 DIV), but the muscarinic receptor reactivity reached peak at 9 DIV and declined significantly at 12 DIV. The results demonstrated that during aging process of primary cultured neutrons, the decline of muscarinic receptor reactivity is likely prior to the decrease of receptor density

Iodine-123 N-methyl-4-iododexetimide: a new radioligand for single-photon emission tomographic imaging of myocardial muscarinic receptors

International Nuclear Information System (INIS)

Hicks, R.J.; Kassiou, M.; Eu, P.; Katsifis, A.G.; Garra, M.; Power, J.; Najdovski, L.; Lambrecht, R.M.

1995-01-01

Cardiac muscarinic receptor ligands suitable for positron emission tomography have previously been characterised. Attempts to develop radioligands of these receptors suitable for single-photon emission tomographic (SPET) imaging have not been successful due to high lung retention and high non-specific binding of previously investigated potential tracers. The purpose of this study was to evaluate the biodistribution and in vivo imaging characteristics of a new radiopharmaceutical, [ 123 I]N-methyl-4-iododexetimide. Biodistribution studies performed in rats showed high cardiac uptake (2.4% ID/g) 10 min after injection with a heart to lung activity ratio of 5:1. Specificity and stereoselectivity of cardiac binding were demonstrated using blocking experiments in rats. Dynamic imaging studies in anaesthetised greyhounds demonstrated rapid and high myocardial uptake and low lung binding with stable heart to lung activity ratios of >2.5:1 between 10 and 30 min, making SPET imaging feasible. Administration of an excess of an unlabelled muscarinic antagonist, methyl-quinuclidinyl benzylate rapidly displaced myocardial activity to background levels and the pharmacologically inactive enantiomer, [ 123 I]N-methyl-4-iodolevetimide, had no detectable cardiac uptake, indicating specific and stereoselective muscarinic receptor binding. SPET revealed higher activity in the inferior than in the anterior wall, this being consistent with previously described regional variation of cardiac parasympathetic innervation. [ 123 I]N-methyl-4-iododexetimide shows promise as an imaging agent for muscarinic receptor distribution in the heart and may be helpful in evaluating diverse cardiac diseases associated with altered muscarinic receptor function, including heart failure and diabetic heart disease. (orig.)

Evolution of the toxins muscarine and psilocybin in a family of mushroom-forming fungi.

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Pawel Kosentka

Full Text Available Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades, the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10-20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.

Evolution of the toxins muscarine and psilocybin in a family of mushroom-forming fungi.

Science.gov (United States)

Kosentka, Pawel; Sprague, Sarah L; Ryberg, Martin; Gartz, Jochen; May, Amanda L; Campagna, Shawn R; Matheny, P Brandon

2013-01-01

Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10-20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.

Two types of muscarinic acetylcholine receptors in Drosophila and other arthropods

DEFF Research Database (Denmark)

Collin, Caitlin Alexis; Hauser, Frank; Gonzalez de Valdivia, Ernesto I

2013-01-01

Muscarinic acetylcholine receptors (mAChRs) play a central role in the mammalian nervous system. These receptors are G protein-coupled receptors (GPCRs), which are activated by the agonists acetylcholine and muscarine, and blocked by a variety of antagonists. Mammals have five mAChRs (m1-m5......). In this study, we cloned two structurally related GPCRs from the fruit fly Drosophila melanogaster, which, after expression in Chinese hamster ovary cells, proved to be muscarinic acetylcholine receptors. One mAChR (the A-type; encoded by gene CG4356) is activated by acetylcholine (EC50, 5 × 10(-8) M......) and muscarine (EC50, 6 × 10(-8) M) and blocked by the classical mAChR antagonists atropine, scopolamine, and 3-quinuclidinyl-benzilate (QNB), while the other (the B-type; encoded by gene CG7918) is also activated by acetylcholine, but has a 1,000-fold lower sensitivity to muscarine, and is not blocked...

Characterization of muscarinic receptor subtypes in human tissues

International Nuclear Information System (INIS)

Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

1988-01-01

The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [ 3 H]Pirenzepine and [ 3 H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M 1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M 1 , the cardiac M 2 and the glandular M 3

Sex-dependent alterations in resting-state cerebral blood flow, amplitude of low-frequency fluctuations and their coupling relationship in schizophrenia.

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Ma, Xiaomei; Wang, Di; Zhou, Yujing; Zhuo, Chuanjun; Qin, Wen; Zhu, Jiajia; Yu, Chunshui

2016-04-01

We aimed to investigate sex-dependent alterations in resting-state relative cerebral blood flow, amplitude of low-frequency fluctuations and relative cerebral blood flow-amplitude of low-frequency fluctuations coupling in patients with schizophrenia. Resting-state functional magnetic resonance imaging and three-dimensional pseudo-continuous arterial spin labeling imaging were performed to obtain resting-state amplitude of low-frequency fluctuations and relative cerebral blood flow in 95 schizophrenia patients and 99 healthy controls. Sex differences in relative cerebral blood flow and amplitude of low-frequency fluctuations were compared in both groups. Diagnostic group differences in relative cerebral blood flow, amplitude of low-frequency fluctuations and relative cerebral blood flow-amplitude of low-frequency fluctuations coupling were compared in male and female subjects, respectively. In both healthy controls and schizophrenia patients, the males had higher relative cerebral blood flow in anterior brain regions and lower relative cerebral blood flow in posterior brain regions than did the females. Compared with multiple regions exhibiting sex differences in relative cerebral blood flow, only the left middle frontal gyrus had a significant sex difference in amplitude of low-frequency fluctuations. In the females, schizophrenia patients exhibited increased relative cerebral blood flow and amplitude of low-frequency fluctuations in the basal ganglia, thalamus and hippocampus and reduced relative cerebral blood flow and amplitude of low-frequency fluctuations in the frontal, parietal and occipital regions compared with those of healthy controls. However, there were fewer brain regions with diagnostic group differences in the males than in the females. Brain regions with diagnostic group differences in relative cerebral blood flow and amplitude of low-frequency fluctuations only partially overlapped. Only the female patients exhibited increased relative cerebral

Cardiac muscarinic receptor overexpression in sudden infant death syndrome.

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Angelo Livolsi

Full Text Available BACKGROUND: Sudden infant death syndrome (SIDS remains the leading cause of death among infants less than 1 year of age. Disturbed expression of some neurotransmitters and their receptors has been shown in the central nervous system of SIDS victims but no biological abnormality of the peripheral vago-cardiac system has been demonstrated to date. The present study aimed to seek vago-cardiac abnormalities in SIDS victims. The cardiac level of expression of muscarinic receptors, as well as acetylcholinesterase enzyme activity were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Left ventricular samples and blood samples were obtained from autopsies of SIDS and children deceased from non cardiac causes. Binding experiments performed with [(3H]NMS, a selective muscarinic ligand, in cardiac membrane preparations showed that the density of cardiac muscarinic receptors was increased as shown by a more than doubled B(max value in SIDS (n = 9 SIDS versus 8 controls. On average, the erythrocyte acetylcholinesterase enzyme activity was also significantly increased (n = 9 SIDS versus 11 controls. CONCLUSIONS: In the present study, it has been shown for the first time that cardiac muscarinic receptor overexpression is associated with SIDS. The increase of acetylcholinesterase enzyme activity appears as a possible regulatory mechanism.

Muscarinic responses of gastric parietal cells

International Nuclear Information System (INIS)

Wilkes, J.M.; Kajimura, M.; Scott, D.R.; Hersey, S.J.; Sachs, G.

1991-01-01

Isolated rabbit gastric glands were used to study the nature of the muscarinic cholinergic responses of parietal cells. Carbachol stimulation of acid secretion, as measured by the accumulation of aminopyrine, was inhibited by the M1 antagonist, pirenzepine, with an IC50 of 13 microM; by the M2 antagonist, 11,2-(diethylamino)methyl-1 piperidinyl acetyl-5,11-dihydro-6H-pyrido 2,3-b 1,4 benzodiazepin-6-one (AF-DX 116), with an IC50 of 110 microM; and by the M1/M3 antagonist, diphenyl-acetoxy-4-methylpiperidinemethiodide, with an IC50 of 35 nM. The three antagonists displayed equivalent IC50 values for the inhibition of carbachol-stimulated production of 14CO2 from radiolabeled glucose, which is a measure of the turnover of the H,K-ATPase, the final step of acid secretion. Intracellular calcium levels were measured in gastric glands loaded with FURA 2. Carbachol was shown to both release calcium from an intracellular pool and to promote calcium entry across the plasma membrane. The calcium entry was inhibitable by 20 microM La3+. The relative potency of the three muscarinic antagonists for inhibition of calcium entry was essentially the same as for inhibition of acid secretion or pump related glucose oxidation. Image analysis of the glands showed the effects of carbachol, and of the antagonists, on intracellular calcium were occurring largely in the parietal cell. The rise in cell calcium due to release of calcium from intracellular stores was inhibited by 4-DAMP with an IC50 of 1.7 nM, suggesting that the release pathway was regulated by a low affinity M3 muscarinic receptor or state; Ca entry and acid secretion are regulated by a high affinity M3 muscarinic receptor or state, inhibited by higher 4-DAMP concentrations, suggesting that it is the steady-state elevation of Ca that is related to parietal cell function rather than the [Ca]i transient

Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

International Nuclear Information System (INIS)

Mak, J.C.; Barnes, P.J.

1990-01-01

Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.

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Joseph, Lauren; Thomsen, Morgane

2017-06-30

Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

Alkylating derivative of oxotremorine interacts irreversibly with the muscarinic receptor

International Nuclear Information System (INIS)

Ehlert, F.J.; Jenden, D.J.; Ringdahl, B.

1984-01-01

A 2-chloroethylamine derivative of oxotremorine was studied in pharmacological experiments and muscarinic receptor binding assays. The compound, N-[4-(2-chloroethylmethylamino)-2-butynyl]-2-pyrrolidone (BM 123), forms an aziridinium ion in aqueous solution at neutral pH that stimulates contractions of guinea pig ileum with a potency similar to that of oxotremorine. Following the initial stimulation, there is a long lasting period of lack of sensitivity of the guinea pig ileum to muscarinic agonists. BM 123 also produces muscarinic effects in vivo. When homogenates of the rat cerebral cortex were incubated with BM 123 and assayed subsequently in muscarinic receptor binding assays, a loss of binding capacity for the muscarinic antagonist, [ 3 H]N-methylscopolamine ([ 3 H]NMS), was noted without a change in affinity. Similar observations were made in [ 3 H]1-3-quinuclidinyl benzilate ([ 3 H]-QNB) binding assays on the forebrains of mice that had been injected with BM 123 24 hr earlier. The loss in receptor capacity for both [ 3 H]NMS and [ 3 H]-QNB was prevented by atropine treatment. Kinetic studies of the interaction of BM 123 with homogenates of the rat cerebral cortex in vitro showed that the half-time for the loss of [ 3 H]-QNB binding sites increased from 10 to 45 min as the concentration of BM 123 decreased from 10 to 1 μM. In contrast to the aziridinium ion, the parent 2-chloroethylamine compound and the alcoholic hydrolysis product were largely devoid of pharmacological and binding activity

Quantitative autoradiographic analysis of muscarinic receptor subtypes and their role in representational memory

International Nuclear Information System (INIS)

Messer, W.S.

1986-01-01

Autoradiographic techniques were used to examine the distribution of muscarinic receptors in rat brain slices. Agonist and selective antagonist binding were examined by measuring the ability for unlabeled ligands to inhibit [ 3 H]-1-QNB labeling of muscarinic receptors. The distribution of high affinity pirenzepine binding sites (M 1 subtype) was distinct from the distribution of high affinity carbamylcholine sites, which corresponded to the M 2 subtype. In a separate assay, the binding profile for pirenzepine was shown to differ from the profile for scopolamine, a classical muscarinic antagonist. Muscarinic antagonists, when injected into the Hippocampus, impaired performance of a representational memory task. Pirenzepine, the M 1 selective antagonist, produced representational memory deficits. Scopolamine, a less selective muscarinic antagonist, caused increases in running times in some animals which prevented a definitive interpretation of the nature of the impairment. Pirenzepine displayed a higher affinity for the hippocampus and was more effective in producing a selective impairment of representational memory than scopolamine. The data indicated that cholinergic activity in the hippocampus was necessary for representation memory function

Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates

DEFF Research Database (Denmark)

Andersen, Maibritt B; Croy, Carrie Hughes; Dencker, Ditte

2015-01-01

Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R)-6-(3-butylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane...... (BuTAC) exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects...

3-(2-Benzofuranyl)quinuclidin-2-ene derivatives: novel muscarinic antagonists.

Science.gov (United States)

Nordvall, G; Sundquist, S; Johansson, G; Glas, G; Nilvebrant, L; Hacksell, U

1996-08-16

A series of 26 derivatives of the novel muscarinic antagonist 3-(2-benzofuranyl)quinuclidin-2-ene (1) has been synthesized and evaluated for muscarinic and antimuscarinic properties. The affinity of the compounds was determined by competition experiments in homogenates of cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs using (-)-[3H]-3-quinuclidinyl benzilate as the radioligand, and the antimuscarinic-potency was determined in a functional assay on isolated guinea pig urinary bladder using carbachol as the agonist. The 5-fluorobenzofuranyl derivative was slightly more potent than 1. The 7-bromo-substituted 8 displayed a 14-fold tissue selectivity ratio for muscarinic receptors in the cortex versus the parotid gland. Comparative molecular field analysis and quantitative structure-activity relationship models were developed for this series of substituted benzofuranyl derivatives.

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

International Nuclear Information System (INIS)

Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

2011-01-01

Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

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Mathew Jobin

2009-04-01

Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

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Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

2017-11-15

Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Biochemical and immunological studies of the Muscarinic acetylcholine receptor

International Nuclear Information System (INIS)

Gainer, M.W.

1985-01-01

Muscarinic acetylcholine receptors were solubilized from bovine brain membranes with 3[3-cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS). A combination of 10 mM CHAPS and 1 M NaCl solubilized 15-40% of the specific receptor binding sites from these membranes. The solubilized receptors displayed high affinity binding of the muscarinic antagonist, [ 3 H]quinuclidinyl benzilate with a K/sub D/ = 300 pM. In addition, the solubilized and retained guanyl nucleotide regulation of agonist binding characteristic of membrane bound receptors. Gel filtration experiments showed that solubilized receptors from cortex and cerebellum had different elution profiles. Analysis by sucrose density gradient centrifugation showed that receptors in the lower molecular weight peak sedimented with a coefficient of 5S. Receptors in the larger molecular weight peak sedimented to the bottom of the gradient. Attempts to purify receptors by chromatography on propylbenzilycholine Sepharose were unsuccessful. The technique used to attach the ligand to the solid support, however, was used to synthesize a PrBCM-BSA conjugate and the conjugate used as an antigen in the production of anti-ligand antibodies. Two anti-PrBCM monoclonal antibodies were isolated that recognize muscarinic but not nicotinic cholinergic ligands. The abilities of the antibodies to recognize other muscarinic ligands indicated the antibodies recognized a portion of PrBCM involved in binding to the receptor. Construction of an antibody affinity resin resulted in the purification of this fragment a minimum of 170 fold

Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

1990-01-01

[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

Muscarinic receptor compensation in hippocampus of alzheimer patients. [Autoradiography

Energy Technology Data Exchange (ETDEWEB)

Nordberg, A; Larsson, C; Adolfsson, R; Alafuzoff, I; Winblad, B [Uppsala Univ. (Sweden)

1983-01-01

The activity of the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) (presynaptic marker) and number of muscarine-like receptor binding sites have been measured in the hippocampus from eight individuals with senile dementia of Alzheimer type (SDAT) and ten controls. A negative correlation (r=0.80; p<0.05) was found between the ChAT activity and the number of muscarine-like receptors in the SDAT group but not in the controls. The findings might indicate an ongoing compensatory receptor mechanism as a response to changes in presynaptic cholinergic activity.

Pre- and postynaptic effects of muscarinic antagonists in the isolated guinea pig ileum

International Nuclear Information System (INIS)

Kilbinger, H.; Weiler, W.; Wessler, I.

1986-01-01

The authors have studied in the guinea-pig ileum whether the presynaptic muscarinic receptors of he cholinergic nerves differ from the postsynaptic muscarinic receptors of tthe longitudinal muscle in their affinities for several muscarinic antagonists. The method of measuring the release of tritium-ACh from the myenteric plexus-longitudinal muscle preparation in tthe guinea-pig ileum in the absence of a chlinesterase inhibitor is described in which two longitudinal muscle strips were incubated in a 2 ml organ bath with tritium-choline are subsequently superfused with Tyrode solution

Allosteric Modulation of Muscarinic Acetylcholine Receptors

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; El-Fakahany, E. E.

2010-01-01

Roč. 3, č. 9 (2010), s. 2838-2860 ISSN 1424-8247 R&D Projects: GA ČR GA305/09/0681 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic acetylcholine receptors * allosteric modulation * Alzheimer´s disease Subject RIV: CE - Biochemistry

Muscarinic receptor M₄ positive allosteric modulators attenuate central effects of cocaine

DEFF Research Database (Denmark)

Dall, Camilla; Weikop, Pia; Dencker, Ditte

2017-01-01

BACKGROUND: Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the hypothesis...... that specific muscarinic M4receptor stimulation can attenuate the discriminative stimulus effects and conditioned rewarding effects of cocaine, measures believed to predict the ability of cocaine and cocaine-associated cues to elicit relapse to drug taking. METHODS: We tested the M4-selective positive...

Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates.

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Maibritt B Andersen

Full Text Available Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R-6-(3-butylthio-1,2,5-thiadiazol-4-yl-1-azabicyclo[3.2.1]octane (BuTAC exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects of BuTAC in primates. To this end, we investigated the effects of BuTAC on d-amphetamine-induced behaviour in antipsychotic-naive Cebus paella monkeys. Possible adverse events of BuTAC, were evaluated in the same monkeys as well as in monkeys sensitized to antipsychotic-induced extrapyramidal side effects. The present data suggests that, the muscarinic receptor ligand BuTAC exhibits antipsychotic-like behaviour in primates. The behavioural data of BuTAC as well as the new biochemical data further substantiate the rationale for the use of muscarinic M1/M2/M4-preferring receptor agonists as novel pharmacological tools in the treatment of schizophrenia.

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M₁, M₂, and M₄ receptor knockout mice

DEFF Research Database (Denmark)

Joseph, Lauren; Thomsen, Morgane

2017-01-01

Muscarinic M1/M4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (SD) effects, but the receptor subtypes mediating those...

Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

NARCIS (Netherlands)

Goepel, M.; Gronewald, A.; Krege, S.; Michel, M. C.

1998-01-01

The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and

Alteration of a motor learning rule under mirror-reversal transformation does not depend on the amplitude of visual error.

Science.gov (United States)

Kasuga, Shoko; Kurata, Makiko; Liu, Meigen; Ushiba, Junichi

2015-05-01

Human's sophisticated motor learning system paradoxically interferes with motor performance when visual information is mirror-reversed (MR), because normal movement error correction further aggravates the error. This error-increasing mechanism makes performing even a simple reaching task difficult, but is overcome by alterations in the error correction rule during the trials. To isolate factors that trigger learners to change the error correction rule, we manipulated the gain of visual angular errors when participants made arm-reaching movements with mirror-reversed visual feedback, and compared the rule alteration timing between groups with normal or reduced gain. Trial-by-trial changes in the visual angular error was tracked to explain the timing of the change in the error correction rule. Under both gain conditions, visual angular errors increased under the MR transformation, and suddenly decreased after 3-5 trials with increase. The increase became degressive at different amplitude between the two groups, nearly proportional to the visual gain. The findings suggest that the alteration of the error-correction rule is not dependent on the amplitude of visual angular errors, and possibly determined by the number of trials over which the errors increased or statistical property of the environment. The current results encourage future intensive studies focusing on the exact rule-change mechanism. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

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Meyyammai Swaminathan

2014-06-01

Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

Vitamin C Deficiency Reduces Muscarinic Receptor Coronary Artery Vasoconstriction and Plasma Tetrahydrobiopterin Concentration in Guinea Pigs

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Gry Freja Skovsted

2017-07-01

Full Text Available Vitamin C (vitC deficiency is associated with increased cardiovascular disease risk, but its specific interplay with arteriolar function is unclear. This study investigates the effect of vitC deficiency in guinea pigs on plasma biopterin status and the vasomotor responses in coronary arteries exposed to vasoconstrictor/-dilator agents. Dunkin Hartley female guinea pigs (n = 32 were randomized to high (1500 mg/kg diet or low (0 to 50 mg/kg diet vitC for 10–12 weeks. At euthanasia, coronary artery segments were dissected and mounted in a wire-myograph. Vasomotor responses to potassium, carbachol, sodium nitroprusside (SNP, U46619, sarafotoxin 6c (S6c and endothelin-1 (ET-1 were recorded. Plasma vitC and tetrahydrobiopterin were measured by HPLC. Plasma vitC status reflected the diets with deficient animals displaying reduced tetrahydrobiopterin. Vasoconstrictor responses to carbachol were significantly decreased in vitC deficient coronary arteries independent of their general vasoconstrictor/vasodilator capacity (p < 0.001. Moreover, in vitC deficient animals, carbachol-induced vasodilator responses correlated with coronary artery diameter (p < 0.001. Inhibition of cyclooxygenases with indomethacin increased carbachol-induced vasoconstriction, suggesting an augmented carbachol-induced release of vasodilator prostanoids. Atropine abolished carbachol-induced vasomotion, supporting a specific muscarinic receptor effect. Arterial responses to SNP, potassium, S6c, U46619 and ET-1 were unaffected by vitC status. The study shows that vitC deficiency decreases tetrahydrobiopterin concentrations and muscarinic receptor mediated contraction in coronary arteries. This attenuated vasoconstrictor response may be linked to altered production of vasoactive arachidonic acid metabolites and reduced muscarinic receptor expression/signaling.

Non-Neuronal Functions of the M2 Muscarinic Acetylcholine Receptor

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Ritva Tikkanen

2013-04-01

Full Text Available Acetylcholine is an important neurotransmitter whose effects are mediated by two classes of receptors. The nicotinic acetylcholine receptors are ion channels, whereas the muscarinic receptors belong to the large family of G protein coupled seven transmembrane helix receptors. Beyond its function in neuronal systems, it has become evident that acetylcholine also plays an important role in non-neuronal cells such as epithelial and immune cells. Furthermore, many cell types in the periphery are capable of synthesizing acetylcholine and express at least some of the receptors. In this review, we summarize the non-neuronal functions of the muscarinic acetylcholine receptors, especially those of the M2 muscarinic receptor in epithelial cells. We will review the mechanisms of signaling by the M2 receptor but also the cellular trafficking and ARF6 mediated endocytosis of this receptor, which play an important role in the regulation of signaling events. In addition, we provide an overview of the M2 receptor in human pathological conditions such as autoimmune diseases and cancer.

New pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors.

Science.gov (United States)

Greig, Nigel H; Reale, Marcella; Tata, Ada M

2013-08-01

The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer' and Sjogren's diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic

Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy

International Nuclear Information System (INIS)

Weckesser, M.; Ziemons, K.; Griessmeier, M.; Sonnenberg, F.; Langen, K.J.; Mueller-Gaertner, H.W.; Hufnagel, A.; Elger, C.E.; Hacklaender, T.; Holschbach, M.

1997-01-01

Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [ 123 I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration. (orig.). With 2 figs., 2 tabs

Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

DEFF Research Database (Denmark)

Fink-Jensen, Anders; Schmidt, Lene S; Dencker, Ditte

2011-01-01

of the striatum, suggesting a role for muscarinic M4 receptors in the motor side effects of antipsychotics, and in the alleviation of these side effects by anticholinergics. Here we investigated the potential role of the muscarinic M4 receptor in catalepsy induced by antipsychotics (haloperidol and risperidone...

Myotropic Effects of Cholinergic Muscarinic Agonists and Antagonists in the Beetle Tenebrio molitor L.

Science.gov (United States)

Chowanski, Szymon; Rosinski, Grzegorz

2017-01-01

In mammals, the cholinergic nervous system plays a crucial role in neuronal regulation of physiological processes. It acts on cells by two types of receptors - nicotinic and muscarinic receptors. Both signal transmission pathways also operate in the central and peripheral cholinergic nervous system of insects. In our pharmacological experiments, we studied the effects of two muscarinic agonists (carbachol, pilocarpine) and two muscarinic antagonists (atropine, scopolamine) on the muscle contractile activity of visceral organs in the beetle, Tenebrio molitor. Both antagonists, when injected to haemolymph at concentration 10-5 M, caused delayed and prolonged cardioinhibitory effects on heart contractility in ortho- and antidromic phases of heart activity in T. molitor pupa what was observed as negative chrono- and inotropic effects. Agonist of muscarinic receptors - carbachol evoked opposite effect and increased contraction rate but only in antidromic phase. Pilocarpine, the second agonist induced weak negative chronotropic effects in the antiand orthodromic phases of heart activity. However, neither agonists had an effect on semi-isolated beetle heart in vitro. Only atropine at the highest tested concentrations slightly decreased the frequency of myocardial contractions. These suggest the regulation of heart activity by muscarinic system indirectly. The tested compounds also affected the contractility of the oviduct and hindgut, but the responses of these organs were varied and depended on the concentration of the applied compounds. These pharmacological experiments suggest the possible modulation of insect visceral muscle contractility by the cholinergic nervous system and indirectly indicate the presence of muscarinic receptor(s) in the visceral organs of the beetle T. molitor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

DEFF Research Database (Denmark)

Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

2010-01-01

Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine's discriminative stimulus...... for cocaine addiction....

SELECTIVITY PROFILE OF SOME RECENT MUSCARINIC ANTAGONISTS IN BOVINE AND GUINEA-PIG TRACHEA AND HEART

NARCIS (Netherlands)

ROFFEL, AF; HAMSTRA, JJ; ELZINGA, CRS; ZAAGSMA, J

1994-01-01

The functional affinities of some recently developed subtype-selective muscarinic antagonists towards bovine tracheal smooth muscle muscarinic M(3) receptors were established and compared to binding affinities for bovine cardiac M(2) and functional affinities for guinea-pig tracheal smooth muscle

Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

Science.gov (United States)

Yoshizawa, Tsuyoshi; Hayashi, Yukio; Yoshida, Akira; Yoshida, Shohei; Ito, Yoshihiko; Yamaguchi, Kenya; Yamada, Shizuo; Takahashi, Satoru

2018-03-01

To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P 2 X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P 2 X receptor were measured by a radioreceptor assay using [N-methyl- 3 H] scopolamine methyl chloride ([ 3 H]NMS) and α,β-methylene-ATP (2,8- 3 H) tetrasodium salt ([ 3 H]α,β-MeATP). In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [ 3 H]NMS and [ 3 H]α,β-MeATP was concurrently increased in the bladder from diabetic rats. Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P 2 X receptors in STZ-induced diabetic rats.

Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

Energy Technology Data Exchange (ETDEWEB)

McPherson, D.W.; Luo, H.; Knapp, F.F. Jr.

1994-06-01

Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.

Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder

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Masaki Ogoda

2016-05-01

Full Text Available Muscarinic and purinergic (P2X receptors play critical roles in bladder urothelium under physiological and pathological conditions. Aim of present study was to characterize these receptors in rat bladder urothelium and detrusor muscle using selective radioligands of [N-methyl-3H]scopolamine methyl chloride ([3H]NMS and αβ-methylene ATP [2,8-3H]tetrasodium salt ([3H]αβ-MeATP. Similar binding parameters for each radioligand were observed in urothelium and detrusor muscle. Pretreatment with N-(2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard mustard revealed co-existence of M2 and M3 receptors, with the number of M2 receptors being larger in the urothelium and detrusor muscle. Intravesical administration of imidafenacin and Dpr-P-4 (N → O (active metabolite of propiverine displayed significant binding of muscarinic receptors in the urothelium and detrusor muscle. The treatment with cyclophosphamide (CYP or resiniferatoxin (RTX resulted in a significant decrease in maximal number of binding sites (Bmax for [3H]NMS and/or [3H]αβ-MeATP in the urothelium and detrusor muscle. These results demonstrated that 1 pharmacological characteristics of muscarinic and P2X receptors in rat bladder urothelium were similar to those in the detrusor muscle, 2 that densities of these receptors were significantly altered by pretreatments with CYP and RTX, and 3 that these receptors may be pharmacologically affected by imidafenacin and Dpr-P-4 (N → O which are excreted in the urine.

Hypoxia increases exercise heart rate despite combined inhibition of β-adrenergic and muscarinic receptors

DEFF Research Database (Denmark)

Siebenmann, Christoph; Rasmussen, Peter; Sørensen, Henrik

2015-01-01

Hypoxia increases the heart rate (HR) response to exercise but the mechanism(s) remain unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate but not combined inhibition of β-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise...... combined β-adrenergic and muscarinic receptor inhibition....

Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer, Parkinson and Lewy body types.

Science.gov (United States)

Perry, E K; Smith, C J; Court, J A; Perry, R H

1990-01-01

Cholinergic nicotinic and muscarinic receptor binding were measured in post mortem human brain tissue, using low (nM) concentrations of (3H)-nicotine to detect predominately the high affinity nicotinic site and (3H)-N-methylscopolamine in the presence and absence of 3 x 10(-4) M carbachol to measure both the low and high affinity agonist subtypes of the muscarinic receptor group. Consistent with most previous reports, the nicotinic but not muscarinic binding was reduced in the different forms of dementia associated with cortical cholinergic deficits, including Alzheimer's and Parkinson's disease, senile dementia of Lewy body type (SDLT) and Down's syndrome (over 50 years). Analysis of (3H)-nicotine binding displaced by a range of carbachol concentrations (10(-9)-10(-3) M) indicated 2 binding sites for nicotine and that the high affinity rather than low affinity site was reduced in Alzheimer's disease. In all 3 cortical areas investigated (temporal, parietal and occipital) there were increases in the low affinity muscarinic site in Parkinson's disease and SDLT but not Alzheimer's disease or middle-aged Down's syndrome. This observation raised the question of whether the presence of neurofibrillary tangles (evident in the latter but not former 2 disorders) is incompatible with denervation-induced muscarinic supersensitivity in cholinoceptive neurons which include cortical pyramids generally affeted by tangle formation.

Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca2+ Signaling in Mouse Aortic Endothelium

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François-Xavier Boittin

2013-02-01

Full Text Available Background/Aims: Smooth muscle tone is controlled by Ca2+ signaling in the endothelial layer. Mouse endothelial cells are interconnected by gap junctions made of Connexin40 (Cx40 and Cx37, which allow the exchange of signaling molecules to coordinate their activity. Here, we investigated the role of Cx40 in the endothelial Ca2+ signaling of the mouse aorta. Methods: Ca2+ imaging was performed on intact aortic endothelium from both wild type (Cx40+/+ and Connexin40-deficient (Cx40 -/- mice. Results: Acetylcholine (ACh induced early fast and high amplitude Ca2+ transients in a fraction of endothelial cells expressing the M3 muscarinic receptors. Inhibition of intercellular communication using carbenoxolone or octanol fully blocked the propagation of ACh-induced Ca2+ transients toward adjacent cells in WT and Cx40-/- mice. As compared to WT, Cx40-/- mice displayed a reduced propagation of ACh-induced Ca2+ waves, indicating that Cx40 contributes to the spreading of Ca2+ signals. The propagation of those Ca2+ responses was not blocked by suramin, a blocker of purinergic ATP receptors, indicating that there is no paracrine effect of ATP release on the Ca2+ waves. Conclusions: Altogether our data show that Cx40 and Cx37 contribute to the propagation and amplification of the Ca2+ signaling triggered by ACh in endothelial cells expressing the M3 muscarinic receptors.

Decreased ipsilateral [123I]iododexetimide binding to cortical muscarinic receptors in unilaterally 6-hydroxydopamine lesioned rats

International Nuclear Information System (INIS)

Knol, Remco J.J.; Bruin, Kora de; Opmeer, Brent; Voorn, Pieter; Jonker, Allert J.; Eck-Smit, Berthe L.F. van; Booij, Jan

2014-01-01

Introduction: Dysfunction of the cholinergic neurotransmitter system is present in Parkinson’s disease, Parkinson’s disease related dementia and dementia with Lewy bodies, and is thought to contribute to cognitive deficits in these patients. In vivo imaging of the cholinergic system in these diseases may be of value to monitor central cholinergic disturbances and to select cases in which treatment with cholinesterase inhibitors could be beneficial. The muscarinic receptor tracer [ 123 I]iododexetimide, predominantly reflecting M 1 receptor binding, may be an appropriate tool for imaging of the cholinergic system by means of SPECT. In this study, we used [ 123 I]iododexetimide to study the effects of a 6-hydroxydopamine lesion (an animal model of Parkinson’s disease) on the muscarinic receptor availability in the rat brain. Methods: Rats (n = 5) were injected in vivo at 10–13 days after a confirmed unilateral 6-hydroxydopamine lesion. Muscarinic receptor availability was measured bilaterally in multiple brain areas on storage phosphor images by region of interest analysis. Results: Autoradiography revealed a consistent and statistically significant lower [ 123 I]iododexetimide binding in all examined neocortical areas on the ipsilateral side of the lesion as compared to the contralateral side. In hippocampal and subcortical areas, such asymmetry was not detected. Conclusions: This study suggests that evaluation of muscarinic receptor availability in dopamine depleted brains using [ 123 I]iododexetimide is feasible. We conclude that 6-hydroxydopamine lesions induce a decrease of neocortical muscarinic receptor availability. We hypothesize that this arises from down regulation of muscarinic postsynaptic M 1 receptors due to hyperactivation of the cortical cholinergic system in response to dopamine depletion. Advances in knowledge: In rats, dopamine depletion provokes a decrease in neocortical muscarinic receptor availability, which is evaluable by [ 123 I

Decrease in the number of rat brain dopamine and muscarinic receptors after chronic alcohol intake

International Nuclear Information System (INIS)

Syvaelahti, E.K.G.; Hietala, J.; Roeyttae, M.; Groenroos, J.

1988-01-01

The effect of 32 weeks' alcohol treatment on the number and affinity of dopamine and muscarinic receptor sites in rat striatum were measured using 3 H-spiperone and 3 H-quinuclidinylbenzilate ( 3 H-QNB) as radioligans. The number of dopamine receptor sites was 38 per cent and the number of muscarinic receptor sites 36 per cent lower in the alcohol group than in control rats. The differences in receptor affinities were less marked. In conclusion, a long-term alcohol intake with rather moderate doses seems to induce a pronounced down-regulation in dopamine and muscarinic receptor systems in rat striatum. (author)

The binding of [3H]AF-DX 384 to rat ileal smooth muscle muscarinic receptors

International Nuclear Information System (INIS)

Entzeroth, M.; Mayer, N.

1991-01-01

The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-[2-[-(8-dipropylamino)methyl]-1-piperidinyl-ethyl-amino-carbonyl]-6H-pyrido [2,3-b] [1,4]benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of [3H]AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that [3H]AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations

The role of muscarinic cholinergic signaling in cost-benefit decision making

Science.gov (United States)

Fobbs, Wambura

Animals regularly face decisions that affect both their immediate success and long term survival. Such decisions typically involve some form of cost-benefit analysis and engage a number of high level cognitive processes, including learning, memory and motivational influences. While decision making has been a focus of study for over a century, it's only in the last 20 years that researchers have begun to identify functional neural circuits that subserve different forms of cost-benefit decision making. Even though the cholinergic system is both functionally and anatomically positioned to modulate cost-benefit decision circuits, the contribution of the cholinergic system to decision making has been little studied. In this thesis, I investigated the cognitive and neural contribution of muscarinic cholinergic signaling to cost-benefit decision making. I, first, re-examined the effects of systemic administration of 0.3 mg/kg atropine on delay and probability discounting tasks and found that blockade of muscarinic acetylcholine receptors by atropine induced suboptimal choices (impulsive and risky) in both tasks. Since the effect on delay discounting was restricted to the No Cue version of the delay discounting task, I concluded that muscarinic cholinergic signaling mediates both forms of cost-benefit decision making and is selectively engaged when decisions require valuation of reward options whose costs are not externally signified. Second, I assessed the impact of inactivating the nucleus basalis (NBM) on both forms decision making and the effect of injecting atropine locally into the orbitofrontal cortex (OFC), basolateral amygdala (BLA), or nucleus accumbens (NAc) core during the No Cue version of the delay discounting task. I discovered that although NBM inactivation failed to affect delay discounting, it induced risk aversion in the probability discounting task; and blockade of intra- NAc core, but not intra-OFC or intra-BLA, muscarinic cholinergic signaling lead to

Effects of muscarinic blockade in perirhinal cortex during visual recognition

Science.gov (United States)

Tang, Yi; Mishkin, Mortimer; Aigner, Thomas G.

1997-01-01

Stimulus recognition in monkeys is severely impaired by destruction or dysfunction of the perirhinal cortex and also by systemic administration of the cholinergic-muscarinic receptor blocker, scopolamine. These two effects are shown here to be linked: Stimulus recognition was found to be significantly impaired after bilateral microinjection of scopolamine directly into the perirhinal cortex, but not after equivalent injections into the laterally adjacent visual area TE or into the dentate gyrus of the overlying hippocampal formation. The results suggest that the formation of stimulus memories depends critically on cholinergic-muscarinic activation of the perirhinal area, providing a new clue to how stimulus representations are stored. PMID:9356507

G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na+ channel interaction

International Nuclear Information System (INIS)

Cohen-Armon, M.; Garty, H.; Sokolovsky, M.

1988-01-01

The authors previous experiments in membranes prepared from rat heart and brain led them to suggest that the binding of agonist to the muscarinic receptors and to the Na + channels is a coupled event mediated by guanine nucleotide binding protein(s) [G-protein(s)]. These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of [ 3 H] acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of [ 3 H]batrachotoxin to Na + channel(s) in the presence of the muscarinic agonists; and (iii) muscarinically induced 22 Na + uptake in the presence and absence of tetrodotoxin, which blocks Na + channels. The findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na + channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components-receptor, G-protein, and Na + channel-is such that at resting potential the muscarinic receptor induces opening of Na + channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues

New advances in pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors

Science.gov (United States)

Greig, Nigel H.; Reale, Marcella; Tata, Ada Maria

2016-01-01

The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer’ and Sjogren’s diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic

Muscarinic Receptor Agonists and Antagonists

Directory of Open Access Journals (Sweden)

David R. Kelly

2001-02-01

Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease

DEFF Research Database (Denmark)

Dencker, Ditte; Thomsen, Morgane; Wörtwein, Gitta

2011-01-01

's disease and drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as potential targets for the treatment of these disorders classically viewed as "dopamine based...... site. Such agents may lead to the development of novel classes of drugs useful for the treatment of psychosis, drug abuse and Parkinson's disease. The present review highlights recent studies carried out using muscarinic receptor knock-out mice and new subtype-selective allosteric ligands to assess...... the roles of M(1), M(4), and M(5) receptors in various central processes that are under strong dopaminergic control. The outcome of these studies opens new perspectives for the use of novel muscarinic drugs for several severe disorders of the CNS....

Role of protein glycosylation on the expression of muscarinic receptors of N4TG1 neuroblastoma cells

International Nuclear Information System (INIS)

Ahmad, A.; Chiang, P.K.

1986-01-01

Muscarinic acetylcholine receptors (mAChR) are glycoproteins. Experiments were conducted to determine whether active glycosylation of proteins in N4TG1 neuroblastoma cells could affect the expression of muscarinic receptors on the cell surface. The binding of radioactive N-methylscopolamine, a membrane impermeable ligand, to intact cells was used as a measure of mAChR. In the presence of the inhibitors of glycosylation, such as tunicamycin, monensin and amphomycin, N-linked glycosylation of proteins in the N4TG1 cells was inhibited, as measured by the incorporation of radioactive glucosamine or mannose in proteins. At the concentrations of tunicamycin and monensin used, the glycosylation of proteins after 3 hours were drastically reduced, but the number of mAChR in the cells was not altered. The apparent lack of effect within a short incubation period could be attributed to the presence of preformed oligosaccharide dolichol readily available for N-glycosylation. However, after 24 hours, tunicamycin (0.05 μg/ml) caused a decrease in the number of mAChR by 17% without having any effect on protein synthesis. Therefore, de novo glycosylation of proteins may be required for the expression of mAChR receptors in the N4TG1 neuroblastoma cell surface

Two types of muscarinic acetylcholine receptors in Drosophila and other arthropods.

Science.gov (United States)

Collin, Caitlin; Hauser, Frank; Gonzalez de Valdivia, Ernesto; de Valdivia, Ernesto Gonzalez; Li, Shizhong; Reisenberger, Julia; Carlsen, Eva M M; Khan, Zaid; Hansen, Niels O; Puhm, Florian; Søndergaard, Leif; Niemiec, Justyna; Heninger, Magdalena; Ren, Guilin R; Grimmelikhuijzen, Cornelis J P

2013-09-01

Muscarinic acetylcholine receptors (mAChRs) play a central role in the mammalian nervous system. These receptors are G protein-coupled receptors (GPCRs), which are activated by the agonists acetylcholine and muscarine, and blocked by a variety of antagonists. Mammals have five mAChRs (m1-m5). In this study, we cloned two structurally related GPCRs from the fruit fly Drosophila melanogaster, which, after expression in Chinese hamster ovary cells, proved to be muscarinic acetylcholine receptors. One mAChR (the A-type; encoded by gene CG4356) is activated by acetylcholine (EC50, 5 × 10(-8) M) and muscarine (EC50, 6 × 10(-8) M) and blocked by the classical mAChR antagonists atropine, scopolamine, and 3-quinuclidinyl-benzilate (QNB), while the other (the B-type; encoded by gene CG7918) is also activated by acetylcholine, but has a 1,000-fold lower sensitivity to muscarine, and is not blocked by the antagonists. A- and B-type mAChRs were also cloned and functionally characterized from the red flour beetle Tribolium castaneum. Recently, Haga et al. (Nature 2012, 482: 547-551) published the crystal structure of the human m2 mAChR, revealing 14 amino acid residues forming the binding pocket for QNB. These residues are identical between the human m2 and the D. melanogaster and T. castaneum A-type mAChRs, while many of them are different between the human m2 and the B-type receptors. Using bioinformatics, one orthologue of the A-type and one of the B-type mAChRs could also be found in all other arthropods with a sequenced genome. Protostomes, such as arthropods, and deuterostomes, such as mammals and other vertebrates, belong to two evolutionarily distinct lineages of animal evolution that split about 700 million years ago. We found that animals that originated before this split, such as cnidarians (Hydra), had two A-type mAChRs. From these data we propose a model for the evolution of mAChRs.

Loss of muscarinic receptors and of stimulated phospholipid labeling in ibotenate-treated hippocampus

International Nuclear Information System (INIS)

Fisher, S.K.; Frey, K.A.; Agranoff, B.W.

1981-01-01

The stimulation of phospholipid labeling by muscarinic agonists has been examined in nerve ending preparations from lesioned hippocampus in order to investigate the synaptic locus of the effect. Unilateral injections of the neurotoxin, ibotenic acid, into the hippocampus resulted in an extensive loss of nerve cells from both the dentate gyrus and hippocampus on the lesioned side and a parallel loss of muscarinic receptors as revealed by [ 3 H]quinuclidinyl benzilate autoradiography. Homogenates and nerve ending fractions prepared from the lesioned side of the hippocampus possessed a reduced specific activity (expressed per milligram of protein) of glutamic acid decarboxylase as well as a reduced number of muscarinic receptors compared with the control side. By contrast, choline acetyltransferase activity was either unchanged or slightly increased on the lesioned side. Although there was a reduced yield (25%) of nerve endings from the lesioned side, the specific activity of 32 Pi incorporation into phospholipids in the absence of added carbachol was comparable to that of the control side. There was, however, a marked reduction in the carbachol stimulation of phosphatidic acid and phosphatidylinositol labeling in nerve ending fractions obtained from he lesioned hippocampus. These results indicate that the muscarinic receptors present in nerve ending fractions from hippocampus and implicated in stimulated phospholipid turnover are derived from cholinoceptive intrinsic neurons

Organophosphorus pesticides decrease M2 muscarinic receptor function in guinea pig airway nerves via indirect mechanisms.

Directory of Open Access Journals (Sweden)

Becky J Proskocil

Full Text Available BACKGROUND: Epidemiological studies link organophosphorus pesticide (OP exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on peripheral neurons via similar direct mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Intravenous administration of paraoxon, but not parathion, caused acute frequency-dependent potentiation of vagally-induced bronchoconstriction and increased electrical field stimulation (EFS-induced contractions in isolated trachea independent of AChE inhibition. However, paraoxon had no effect on vagally-induced bradycardia in intact guinea pigs or EFS-induced contractions in isolated ileum, suggesting mechanisms other than pharmacologic antagonism of M2 receptors. Paraoxon did not alter M2 receptor expression in cultured cells at the mRNA or protein level as determined by quantitative RT-PCR and radio-ligand binding assays, respectively. Additionally, a biotin-labeled fluorophosphonate, which was used as a probe to identify molecular targets phosphorylated by OPs, did not phosphorylate proteins in guinea pig cardiac membranes that were recognized by M2 receptor antibodies. CONCLUSIONS/SIGNIFICANCE: These data indicate that neither direct pharmacologic antagonism nor downregulated expression of M2 receptors contributes to OP inhibition of M2 function in airway nerves, adding to the growing evidence of non-cholinergic mechanisms of OP neurotoxicity.

Role of muscarinic receptor antagonists in urgency and nocturia

NARCIS (Netherlands)

Michel, Martin C.; de La Rosette, Jean J. M. C. H.

2005-01-01

The overactive bladder (OAB) syndrome is defined as urgency, with or without urgency incontinence, usually accompanied by frequency and nocturia. Muscarinic receptor antagonists are the most established form of treatment for OAB, but until recently their effectiveness was only confirmed for symptoms

Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

Science.gov (United States)

Nichols, Justin A.

2011-12-01

Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

COLOCALIZATION OF MUSCARINIC AND NICOTINIC RECEPTORS IN CHOLINOCEPTIVE NEURONS OF THE SUPRACHIASMATIC REGION IN YOUNG AND AGED RATS

NARCIS (Netherlands)

VANDERZEE, EA; STREEFLAND, C; STROSBERG, AD; SCHRODER, H; LUITEN, PGM; Schröder, H.

1991-01-01

In the present study muscarinic and nicotinic cholinergic receptors in the SCN region were demonstrated and analyzed, employing monoclonal antibodies to purified muscarinic and nicotinic cholinergic receptor proteins. A near-total colocalization of the two acetylcholine receptor subclasses in

Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber).

Science.gov (United States)

Jørgensen, Kristine B; Krogh-Jensen, Karen; Pickering, Darryl S; Kanui, Titus I; Abelson, Klas S P

2016-01-01

The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1-5 of the naked mole-rat were compared to that of the house mouse (Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [(3)H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.

An Anti-Nicotinic Cognitive Challenge Model using Mecamylamine in Comparison with the Anti-Muscarinic Cognitive Challenge using Scopolamine

NARCIS (Netherlands)

Baakman, A. C.; Alvarez-jimenez, R.; Rissmann, R.; Klaassen, E. S.; Stevens, J.; Goulooze, S. C.; Burger, J.; Swart, E. L.; Van Gerven, J. M. A.; Groeneveld, G. J.

Aims The muscarinic acetylcholine receptor antagonist scopolamine is often used for proof-of-pharmacology studies with pro-cognitive compounds. From a pharmacological point of view, it would seem more rational to use a nicotinic rather than a muscarinic anticholinergic challenge to prove

Role of dopamine receptor and muscarinic acetylcholine receptor blockade in the antiapomorphine action of neuroleptics

Energy Technology Data Exchange (ETDEWEB)

Zharkovskii, A.M.; Langel, Yu.L.; Chereshka, K.S.; Zharkovskaya, T.A.

1987-08-01

The authors analyze the role of dopamine and muscarinic acetylcholine receptor blocking components in the antistereotypic action of neuroleptics with different chemical structure. To determine dopamine-blocking activity in vitro, binding of /sup 3/H-spiperone with membranes of the rat striatum was measured. To study the blocking action of the substances on muscarinic acetylcholine receptors, binding of /sup 3/H-quinuclidinyl benzylate with brain membranes was chosen.

Fluoxetine induces vasodilatation of cerebral arterioles by co-modulating NO/muscarinic signalling

Science.gov (United States)

Ofek, Keren; Schoknecht, Karl; Melamed-Book, Naomi; Heinemann, Uwe; Friedman, Alon; Soreq, Hermona

2012-01-01

Ischaemic stroke patients treated with Selective Serotonin Reuptake Inhibitors (SSRI) show improved motor, cognitive and executive functions, but the underlying mechanism(s) are incompletely understood. Here, we report that cerebral arterioles in the rat brain superfused with therapeutically effective doses of the SSRI fluoxetine showed consistent, dose-dependent vasodilatation (by 1.2 to 1.6-fold), suppressible by muscarinic and nitric oxide synthase (NOS) antagonists [atropine, NG-nitro-l-arginine methyl ester (l-NAME)] but resistant to nicotinic and serotoninergic antagonists (mecamylamine, methylsergide). Fluoxetine administered 10–30 min. following experimental vascular photo-thrombosis increased arterial diameter (1.3–1.6), inducing partial, but lasting reperfusion of the ischaemic brain. In brain endothelial b.End.3 cells, fluoxetine induced rapid muscarinic receptor-dependent increases in intracellular [Ca2+] and promoted albumin- and eNOS-dependent nitric oxide (NO) production and HSP90 interaction. In vitro, fluoxetine suppressed recombinant human acetylcholinesterase (rhAChE) activity only in the presence of albumin. That fluoxetine induces vasodilatation of cerebral arterioles suggests co-promotion of endothelial muscarinic and nitric oxide signalling, facilitated by albumin-dependent inhibition of serum AChE. PMID:22697296

Highly specific detection of muscarinic M3 receptor, G protein interaction and intracellular trafficking in human detrusor using Proximity Ligation Assay (PLA).

Science.gov (United States)

Berndt-Paetz, Mandy; Herbst, Luise; Weimann, Annett; Gonsior, Andreas; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

2018-05-01

Muscarinic acetylcholine receptors (mAChRs) regulate a number of important physiological functions. Alteration of mAChR expression or function has been associated in the etiology of several pathologies including functional bladder disorders (e.g bladder pain syndrome/interstitial cystitis - BPS/IC). In a previous study we found specific mAChR expression patterns associated with BPS/IC, while correlation between protein and gene expression was lacking. Posttranslational regulatory mechanisms, e.g. altered intracellular receptor trafficking, could explain those differences. In addition, alternative G protein (GP) coupling could add to the pathophysiology via modulation of muscarinic signaling. In our proof-of-principle study, we addressed these questions in situ. We established PLA in combination with confocal laserscanning microscopy (CLSM) and 3D object reconstruction for highly specific detection and analysis of muscarinic 3 receptors (M3), G protein (GP) coupling and intracellular trafficking in human detrusor samples. Paraffin sections of formalin-fixed bladder tissue (FFPE) of BPS/IC patients receiving transurethral biopsy were examined by Cy3-PLA for M3 expression, coupling of M3 to GPs (G αq/11 , G αs , G αi ) and interaction of M3 with endocytic regulator proteins. Membranes were labeled with wheat germ agglutinin-Alexa Fluor ® 488, nuclei were stained with DAPI. Object density and co-localization were analyzed in 3D-reconstruction of high resolution confocal z-stacks. Confocal image stack processing resulted in well demarcated objects. Calculated receptor densities correlated significantly with existing confocal expression data, while significantly improved specificity of M3 detection by PLA was verified using bladder tissue samples from transgenic mice. 50-60% of the M3 receptor complexes were plasma membrane associated in human bladder detrusor. Application of PLA for M3 and GPs allowed visualization of M3-GP interactions and revealed individual GP

Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection.

Science.gov (United States)

Mathieson, Sean R; Livingstone, Vicki; Low, Evonne; Pressler, Ronit; Rennie, Janet M; Boylan, Geraldine B

2016-10-01

Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Post-phenobarbital seizures showed significantly lower amplitude (pphenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of agonist efficacy on desensitization of phosphoinositide hydrolysis mediated by m1 and m3 muscarinic receptors expressed in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Hu, J.; Wang, S.Z.; el-Fakahany, E.E.

1991-01-01

Muscarinic receptor agonist-induced desensitization of phosphoinositide (PI) hydrolysis and loss of receptors were studied in Chinese hamster ovary (CHO) cells transfected with the m1 and m3 muscarinic receptor genes. Long-term exposure to the full agonist carbamylcholine (CBC) resulted in a time-dependent attenuation of the maximal PI response and a decrease in agonist potency. This desensitization was accompanied by a parallel loss of maximal ligand binding without an alteration of the binding affinity. The time course of both receptor desensitization and down-regulation was similar in m1 and m3 CHO cells. The PI response to the partial agonist McN-A-343 (McN) in m1 cells was more sensitive to desensitization by CBC than the response to the latter agonist, and this desensitization was faster than receptor down-regulation. Desensitization of the PI response to McN was reflected as a decrease in the maximal response without a marked change in potency. McN induced slow desensitization of the PI response to CBC but a much faster desensitization of its own response. Our data provide evidence that although muscarinic agonist-induced desensitization of PI hydrolysis in CHO cells is due mainly to loss of receptors, there are other important factors which play a role in this process, e.g., receptor-effector uncoupling. The relative contribution of these different mechanisms depends on the efficacy of the agonists used for the receptor desensitization and activation steps

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

1984-01-01

[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

Energy Technology Data Exchange (ETDEWEB)

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

1984-08-01

(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

Comparative study of muscarinic acetylcholine receptors of human and rat cortical glial cells

International Nuclear Information System (INIS)

Demushkin, V.P.; Burbaeva, G.S.; Dzhaliashvili, T.A.; Plyashkevich, Y.G.

1985-01-01

The aim of the present investigation was a comparative studyof muscarinic acetylcholine receptors in human and rat glial cells. ( 3 H)Quinuclidinyl-benzylate (( 3 H)-QB), atropine, platiphylline, decamethonium, carbamylcholine, tubocurarine, and nicotine were used. The glial cell fraction was obtained from the cerebral cortex of rats weighing 130-140 g and from the frontal pole of the postmortem brain from men aged 60-70 years. The use of the method of radioimmune binding of ( 3 H)-QB with human and rat glial cell membranes demonstrated the presence of a muscarinic acetylcholine receptor in the glial cells

Muscarinic acetylcholine receptor subtypes: localization and structure/function

DEFF Research Database (Denmark)

Brann, M R; Ellis, J; Jørgensen, H

1993-01-01

Based on the sequence of the five cloned muscarinic receptor subtypes (m1-m5), subtype selective antibody and cDNA probes have been prepared. Use of these probes has demonstrated that each of the five subtypes has a markedly distinct distribution within the brain and among peripheral tissues...... are described, as well as the implied structures of these functional domains....

Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.

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Luis Segu

Full Text Available Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4, but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR(4 knock-out (KO and wild-type (WT mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4 control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR(4 KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT, the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4 KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR(4 KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4 to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4 aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4 mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.

Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome.

Science.gov (United States)

Weber, Stefanie; Thiele, Holger; Mir, Sevgi; Toliat, Mohammad Reza; Sozeri, Betül; Reutter, Heiko; Draaken, Markus; Ludwig, Michael; Altmüller, Janine; Frommolt, Peter; Stuart, Helen M; Ranjzad, Parisa; Hanley, Neil A; Jennings, Rachel; Newman, William G; Wilcox, Duncan T; Thiel, Uwe; Schlingmann, Karl Peter; Beetz, Rolf; Hoyer, Peter F; Konrad, Martin; Schaefer, Franz; Nürnberg, Peter; Woolf, Adrian S

2011-11-11

Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Effect of paraoxon on muscarinic, dopamine and γ-aminobutyric acid receptors of brain and sensitivity to muscarinic antagonists

International Nuclear Information System (INIS)

Fernando, J.C.R.; Hoskins, B.; Ho, I.K.

1986-01-01

Several acetylcholinesterase (AChE) inhibitors decrease muscarinic cholinergic (mACh) receptors in the brain, alteration of dopamine (DA) and γ-aminobutyric acid (GABA) receptors after AChE inhibition was also reported. In view of the important interactions among DA, GABA and ACh systems, whether this is a common effect of AChE inhibitors should be established. They report the effect of the AChE inhibitor, paraoxon, on DA, GABA and mACh receptors in the rat. The binding of 3 H-QNB (for mACh), 3 H-spiperone (for DA) and 3 H-muscimol (for GABA) to striatal and hippocampal membranes was analyzed. Also, behavioral sensitivity to atropine was studied. Twenty-four hr after a single dose (0.75 mg/kg, s.c.) of paraoxon, the density of mACh receptors in the striatum was decreased but, at 3 days, no change was seen. In the hippocampus, the mACh receptors were not affected. Repeated treatment with paraoxon (0.3 mg/kg, 48 hourly) for 2 weeks reduced the mACh receptor density in both regions. Neither single nor repeated paraoxon treatment had an effect on DA or GABA receptors. After single or repeated dosing with paraoxon, myoclonus induced by atropine (10 mg/kg, i.p.) was enhanced. The results show rapid downregulation of mACh receptors by paraoxon. DA or GABA, however, appear not to be affected under these treatment regimens

Quantitative autoradiography of muscarinic and benzodiazepine receptors in the forebrain of the turtle, Pseudemys scripta

International Nuclear Information System (INIS)

Schlegel, J.R.; Kriegstein, A.R.

1987-01-01

The distribution of muscarinic and benzodiazepine receptors was investigated in the turtle forebrain by the technique of in vitro receptor autoradiography. Muscarinic binding sites were labeled with 1 nM 3 H-quinuclidinyl benzilate ( 3 H-QNB), and benzodiazepine sites were demonstrated with the aid of 1 nM 3 H-flunitrazepam ( 3 H-FLU). Autoradiograms generated on 3 H-Ultrofilm apposed to tissue slices revealed regionally specific distributions of muscarinic and benzodiazepine binding sites that are comparable with those for mammalian brain. Dense benzodiazepine binding was found in the anterior olfactory nucleus, the lateral and dorsal cortices, and the dorsal ventricular ridge (DVR), a structure with no clear mammalian homologue. Muscarinic binding sites were most dense in the striatum, accumbens, DVR, lateral geniculate, and the anterior olfactory nucleus. Cortical binding sites were studied in greater detail by quantitative analysis of autoradiograms generated by using emulsion-coated coverslips. Laminar gradients of binding were observed that were specific for each radioligand; 3 H-QNB sites were most dense in the inner molecular layer in all cortical regions, whereas 3 H-FLU binding was generally most concentrated in the outer molecular layer and was least dense through all layers in the dorsomedial cortex. Because pyramidal cells are arranged in register in turtle cortex, the laminar patterns of receptor binding may reflect different receptor density gradients along pyramidal cell dendrites

Muscarinic receptor antagonists for overactive bladder treatment: does one fit all?

NARCIS (Netherlands)

Witte, Lambertus P. W.; Mulder, Wilhelmina M. C.; de La Rosette, Jean J. M. C. H.; Michel, Martin C.

2009-01-01

Purpose of review To review evidence and regulatory dosing recommendations for muscarinic receptor antagonists used in the treatment of overactive bladder symptom complex (darifenacin, fesoterodine oxybutynin propiverine solifenacin tolterodine trospium) in special patient populations. Recent

The pharmacological rationale for combining muscarinic receptor antagonists and beta-adrenoceptor agonists in the treatment of airway and bladder disease

NARCIS (Netherlands)

Dale, Philippa R.; Cernecka, Hana; Schmidt, Martina; Dowling, Mark R.; Charlton, Steven J.; Pieper, Michael P.; Michel, Martin C.

Muscarinic receptor antagonists and beta-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and beta-adrenoceptors are physiological antagonists for

Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

DEFF Research Database (Denmark)

Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

2010-01-01

substituted for cocaine and enhanced its discriminative stimulus. Conversely, muscarinic agonists blunted cocaine discrimination and abolished cocaine self-administration with varying effects on food-maintained behavior. Specifically, increasing selectivity for the M(1) subtype (oxotremorine ...'s abuse-related effects, whereas non-M(1)/M(4) receptors probably contribute to undesirable effects of muscarinic stimulation. These data provide the first demonstration of anticocaine effects of systemically applied, M(1) receptor agonists and suggest the possibility of a new approach to pharmacotherapy...

No changes in lymphocyte muscarinic receptors and platelet monoamine oxidase-B examined as surrogate central nervous system biomarkers in a Faroese children cohort prenatally exposed to methylmercury and polychlorinated biphenyls

DEFF Research Database (Denmark)

Coccini, Teresa; Manzo, Luigi; Debes, Frodi

2009-01-01

Experimental evidence suggests that monoamine oxidase B (MAO-B) and muscarinic cholinergic receptors (mAChRs) are involved in the pathogenesis of neurotoxicity caused by methylmercury and polychlorinated biphenyls (PCBs). Blood samples from 7-year-old exposed children were analyzed for platelet M....../or PCB exposure, whereas these markers are significantly altered in sustained exposure scenarios, as shown by clinical studies in drug addicts or patients treated with psychopharmacological agents....

Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.

Science.gov (United States)

Gainetdinov, R R; Bohn, L M; Walker, J K; Laporte, S A; Macrae, A D; Caron, M G; Lefkowitz, R J; Premont, R T

1999-12-01

G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. Classical cholinergic responses such as hypothermia, hypoactivity, tremor, and salivation were enhanced in GRK5-KO animals. The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.

Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline

DEFF Research Database (Denmark)

Dencker, Ditte; Wörtwein, Gitta; Weikop, Pia

2011-01-01

Disturbances in central dopaminergic neurotransmission are believed to be centrally involved in the pathogenesis of schizophrenia. Central dopaminergic and cholinergic systems interact and the cholinergic muscarinic agonist xanomeline has shown antipsychotic effects in clinical studies. Preclinic...

Vitamin C deficiency reduces muscarinic receptor coronary artery vasoconstriction and plasma tetrahydrobiopterin concentration in guinea pigs

DEFF Research Database (Denmark)

Skovsted, Gry Freja; Tveden-Nyborg, Pernille; Lindblad, Maiken Marie

2017-01-01

Vitamin C (vitC) deficiency is associated with increased cardiovascular disease risk, but its specific interplay with arteriolar function is unclear. This study investigates the effect of vitC deficiency in guinea pigs on plasma biopterin status and the vasomotor responses in coronary arteries...... exposed to vasoconstrictor/-dilator agents. Dunkin Hartley female guinea pigs (n = 32) were randomized to high (1500 mg/kg diet) or low (0 to 50 mg/kg diet) vitC for 10-12 weeks. At euthanasia, coronary artery segments were dissected and mounted in a wire-myograph. Vasomotor responses to potassium......-1 were unaffected by vitC status. The study shows that vitC deficiency decreases tetrahydrobiopterin concentrations and muscarinic receptor mediated contraction in coronary arteries. This attenuated vasoconstrictor response may be linked to altered production of vasoactive arachidonic acid...

Perirhinal Cortex Muscarinic Receptor Blockade Impairs Taste Recognition Memory Formation

Science.gov (United States)

Gutierrez, Ranier; De la Cruz, Vanesa; Rodriguez-Ortiz, Carlos J.; Bermudez-Rattoni, Federico

2004-01-01

The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition…

Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease; impaired vs normal left ventricular function.

NARCIS (Netherlands)

A.F. van den Heuvel; D.J. van Veldhuisen (Dirk); G.L. Bartels; M. van der Ent (Martin); W.J. Remme (Willem)

1999-01-01

textabstractAIMS: In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown.

Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill.

Science.gov (United States)

González, Alfredo; Crittenden, Elizabeth L; García, Dana M

2004-07-13

In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl) carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill

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Crittenden Elizabeth L

2004-07-01

Full Text Available Abstract Background In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. Results The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Conclusions Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

Science.gov (United States)

Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

2010-01-01

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not

Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short term memory task

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Sasha eDevore

2012-09-01

Full Text Available Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for tens to hundreds of seconds. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short-term memory task.

Science.gov (United States)

Devore, Sasha; Manella, Laura C; Linster, Christiane

2012-01-01

Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for 10-100 s. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

Muscarinic receptor blockade in ventral hippocampus and prelimbic cortex impairs memory for socially transmitted food preference.

Science.gov (United States)

Carballo-Márquez, Anna; Vale-Martínez, Anna; Guillazo-Blanch, Gemma; Martí-Nicolovius, Margarita

2009-05-01

Acetylcholine is involved in learning and memory and, particularly, in olfactory tasks, but reports on its specific role in consolidation processes are somewhat controversial. The present experiment sought to determine the effects of blocking muscarinic cholinergic receptors in the ventral hippocampus (vHPC) and the prelimbic cortex (PLC) on the consolidation of social transmission of food preference, an odor-guided relational task that depends on such brain areas. Adult male Wistar rats were bilaterally infused with scopolamine (20 microg/site) immediately after social training and showed impairment, relative to vehicle-injected controls, in the expression of the task measured 24 h after learning. Results indicated that scopolamine in the PLC completely abolished memory, suggesting that muscarinic transmission in this cortical region is crucial for consolidation of recent socially acquired information. Muscarinic receptors in the vHPC contribute in some way to task consolidation, as the rats injected with scopolamine in the vHPC showed significantly lower trained food preference than control rats, but higher than both chance level and that of the PLC-injected rats. Behavioral measures such as social interaction, motivation to eat, neophobia, or exploration did not differ between rats infused with scopolamine or vehicle. Such data suggest a possible differential role of muscarinic receptors in the PLC and the vHPC in the initial consolidation of a naturalistic form of nonspatial relational memory. Copyright 2008 Wiley-Liss, Inc.

Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

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Kang JY

2013-10-01

Full Text Available Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA for 1 month (n = 8–12 per group. We analyzed inflammatory cells and T-helper (Th2 cytokines in bronchoalveolar lavage (BAL fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old mice than in the young (6-week-old mice. Interleukin (IL 4 (IL-4 concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma

The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells

International Nuclear Information System (INIS)

Secondo, Agnese; De Mizio, Mariarosaria; Zirpoli, Laura; Santillo, Mariarosaria; Mondola, Paolo

2008-01-01

The Cu-Zn superoxide dismutase (SOD1) belongs to a family of isoenzymes that are able to dismutate the oxygen superoxide in hydrogen peroxide and molecular oxygen. This enzyme is secreted by many cellular lines and it is also released trough a calcium-dependent depolarization mechanism involving SNARE protein SNAP 25. Using rat pituitary GH3 cells that express muscarinic receptors we found that SOD1 inhibits P-ERK1/2 pathway trough an interaction with muscarinic M1 receptor. This effect is strengthened by oxotremorine, a muscarinic M agonist and partially reverted by pyrenzepine, an antagonist of M1 receptor; moreover this effect is independent from increased intracellular calcium concentration induced by SOD1. Finally, P-ERK1/2 inhibition was accompanied by the reduction of GH3 cell proliferation. These data indicate that SOD1 beside the well studied antioxidant properties can be considered as a neuromodulator able to affect mitogen-activated protein kinase in rat pituitary cells trough a M1 muscarinic receptor

Outline of therapeutic interventions with muscarinic receptor-mediated transmission

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Šantrůčková, Eva; Randáková, Alena; Janíčková, Helena; Zimčík, Pavel; Rudajev, Vladimír; Michal, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

2014-01-01

Roč. 63, Suppl.1 (2014), S177-S189 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GAP304/12/0259; GA MŠk(CZ) 7E10060 Institutional support: RVO:67985823 Keywords : cholinergic transmission * muscarinic receptors * therapy * Alzheimer's disease, * schizophrenia Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014

In vivo and in vitro studies on a muscarinic presynaptic antagonist and postsynaptic agonist: BM-5

International Nuclear Information System (INIS)

Nordstrom, O.; Bartafi, T.; Frieder, B.; Grimm, V.; Ladinsky, H.; Unden, A.

1986-01-01

This paper reports on in vitro and in vivo studies with compound BM-5 which, at proper dosage, could have great potential since it could enhance cholinergic transmission by being a presynaptic antagonist and postsynaptic agonist. Binding studies are described in which tritium-4-NMPB, a muscarinic antagonist, was displaced by compound BM-5 in membranes from striatum, cerebral cortex, cerebellum and hippocampus. The binding data are summarized, which for each brain area involved 86-92 data points evaluated by means of nonlinear regression methods. Compound BM-5 recognized in each brain region a population of high and a population of low affinity binding sites; both of which were labelled with tritium-4-NMPB. It is shown that compound BM-5 causes muscarinic cholinergic agonist-like effects such as redness of the eye, increased motility in the gut, and impairment of locomotor behavior. It also produces muscarinic super-sensitivity upon chronic treatment, and decreases rat striatial ACh content by acute treatment

The A- and B-type muscarinic acetylcholine receptors from Drosophila melanogaster couple to different second messenger pathways

DEFF Research Database (Denmark)

Ren, Guilin Robin; Folke, Jonas; Hauser, Frank

2015-01-01

Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors (GPCRs) that are activated by the agonists acetylcholine and muscarine and blocked by several antagonists, among them atropine. In mammals five mAChRs (m1-m5) exist of which m1, m3, and m5 are coupled to members of the Gq...

Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice.

Science.gov (United States)

Thomsen, Morgane; Caine, Simon Barak

2016-04-05

Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems. Copyright © 2016 Elsevier B.V. All rights reserved.

GABAergic Neurons of the Rat Dorsal Hippocampus Express Muscarinic Acetylcholine Receptors

NARCIS (Netherlands)

van der Zee, E.A.; Luiten, P.G.M.

1993-01-01

The expression of muscarinic acetylcholine receptors (mAChRs) in glutamic acid decarboxylase (GAD)-positive cells in the different strata of CA1, CA3, and the dentate gyrus (DG) of the dorsal hippocampus is examined by way of quantitative immunofluorescent double labeling employing M35, the

Scattering amplitudes in super-renormalizable gravity

International Nuclear Information System (INIS)

Donà, Pietro; Giaccari, Stefano; Modesto, Leonardo; Rachwał, Lesław; Zhu, Yiwei

2015-01-01

We explicitly compute the tree-level on-shell four-graviton amplitudes in four, five and six dimensions for local and weakly nonlocal gravitational theories that are quadratic in both, the Ricci and scalar curvature with form factors of the d’Alembertian operator inserted between. More specifically we are interested in renormalizable, super-renormalizable or finite theories. The scattering amplitudes for these theories turn out to be the same as the ones of Einstein gravity regardless of the explicit form of the form factors. As a special case the four-graviton scattering amplitudes in Weyl conformal gravity are identically zero. Using a field redefinition, we prove that the outcome is correct for any number of external gravitons (on-shell n−point functions) and in any dimension for a large class of theories. However, when an operator quadratic in the Riemann tensor is added in any dimension (with the exception of the Gauss-Bonnet term in four dimensions) the result is completely altered, and the scattering amplitudes depend on all the form factors introduced in the action.

Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

Science.gov (United States)

Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

2014-10-01

This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

Muscarinic supersensibility of anterior pituitary ACTH and beta-endorphin release in major depressive illness

International Nuclear Information System (INIS)

Risch, S.C.; Gillin, J.C.; Janowsky, D.S.

1986-01-01

Since numerious physiological systems display muscarinic receptor supersensitivity in major depressive illnesses, the authors have hypothesize that anterior pituitary release of ACTH and beta-Endorphin immunoreactivity may also be muscarinically supersensitive in depression. The studies were conducted under FDA-approved IND and with local human subjects committee approval. Plasma ACTH concentrations were determined as follows: samples were assayed in duplicate using equilibrium radioimmunoassay utilizing a rabbit anti-porcine ACTH antibody. Significance ofchanges in plasma cortisol, ACTH and beta-endorphin immunoreactivity after physostigmine and saline were determined by repeated measures analysis of variance. In all subject groups, physostigmine (relative to placebo) caused significant increases in plasma concentrations of cortisol, ACTH, and beta-endorphin immonoreactivity

Autoradiography of H-3-pirenzepine and H-3-AFDX-384 in Mouse Brain Regions: Possible Insights into M-1, M-2, and M-4 Muscarinic Receptors Distribution

Czech Academy of Sciences Publication Activity Database

Valuskova, P.; Farar, V.; Forczek, Sándor; Křížová, I.; Mysliveček, J.

2018-01-01

Roč. 9, FEB 20 (2018), č. článku 124. ISSN 1663-9812 Institutional support: RVO:61389030 Keywords : 3 h-afdx-384 * 3 H-pirenzepine * 3 h-qnb * Autoradiography * M muscarinic receptor 1 * M muscarinic receptor 2 * M muscarinic receptor 4 Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.400, year: 2016

Muscarinic Acetylcholine Receptors Act in Synergy to Facilitate Learning and Memory

Science.gov (United States)

Leaderbrand, Katherine; Chen, Helen J.; Corcoran, Kevin A.; Guedea, Anita L.; Jovasevic, Vladimir; Wess, Jurgen; Radulovic, Jelena

2016-01-01

Understanding how episodic memories are formed and retrieved is necessary if we are to treat disorders in which they malfunction. Muscarinic acetylcholine receptors (mAChR) in the hippocampus and cortex underlie memory formation, but there is conflicting evidence regarding their role in memory retrieval. Additionally, there is no consensus on…

Increased cocaine self-administration in M4 muscarinic acetylcholine receptor knockout mice

DEFF Research Database (Denmark)

Schmidt, Lene Sørensen; Thomsen, Morgane; Weikop, Pia

2011-01-01

Rationale The reinforcing effects of cocaine are mediated by the mesolimbic dopamine system. Behavioral and neurochemical studies have shown that the cholinergic muscarinic M4 receptor subtype plays an important role in regulation of dopaminergic neurotransmission. Objectives Here we investigated...... of drug addiction...

Venoms of South Asian hump-nosed pit vipers (Genus: Hypnale cause muscarinic effects in BALB/c mice

Directory of Open Access Journals (Sweden)

A Silva

2014-03-01

Full Text Available Although clinical, in-vivo and in-vitro studies suggest the necrotic, haemorrhagic, pro-coagulant and nephrotoxic effects of South Asian Hump nosed pit vipers, reports on neurotoxic properties are limited to a single in-vitro study. Using BALB/c mice, for the first time, here we demonstrate the signs of envenoming suggestive of possible muscarinic effects of the venoms of all three Hypnale species. Further, we demonstrate that the muscarinic effects are occurred at lower venom doses by H. hypnale venom, compared to H. nepa and H. zara.

Biological sex influences learning strategy preference and muscarinic receptor binding in specific brain regions of prepubertal rats.

Science.gov (United States)

Grissom, Elin M; Hawley, Wayne R; Hodges, Kelly S; Fawcett-Patel, Jessica M; Dohanich, Gary P

2013-04-01

According to the theory of multiple memory systems, specific brain regions interact to determine how the locations of goals are learned when rodents navigate a spatial environment. A number of factors influence the type of strategy used by rodents to remember the location of a given goal in space, including the biological sex of the learner. We recently found that prior to puberty male rats preferred a striatum-dependent stimulus-response strategy over a hippocampus-dependent place strategy when solving a dual-solution task, while age-matched females showed no strategy preference. Because the cholinergic system has been implicated in learning strategy and is known to be sexually dimorphic prior to puberty, we explored the relationship between learning strategy and muscarinic receptor binding in specific brain regions of prepubertal males and female rats. We confirmed our previous finding that at 28 days of age a significantly higher proportion of prepubertal males preferred a stimulus-response learning strategy than a place strategy to solve a dual-solution visible platform water maze task. Equal proportions of prepubertal females preferred stimulus-response or place strategies. Profiles of muscarinic receptor binding as assessed by autoradiography varied according to strategy preference. Regardless of biological sex, prepubertal rats that preferred stimulus-response strategy exhibited lower ratios of muscarinic receptor binding in the hippocampus relative to the dorsolateral striatum compared to rats that preferred place strategy. Importantly, much of the variance in this ratio was related to differences in the ventral hippocampus to a greater extent than the dorsal hippocampus. The ratios of muscarinic receptors in the hippocampus relative to the basolateral amygdala also were lower in rats that preferred stimulus-response strategy over place strategy. Results confirm that learning strategy preference varies with biological sex in prepubertal rats with males

The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming.

Science.gov (United States)

Gamberini, Maria Thereza; Bolognesi, Maria Laura; Nasello, Antonia Gladys

2012-12-07

The interaction between dopaminergic and cholinergic pathways in the induction of behavioral responses has been previously established. In the brain, M2 receptors are found predominantly in presynaptic cholinergic neurons as autoreceptors, and in dopaminergic neurons as heteroceptors, suggesting a control role of acetylcholine and dopamine release, respectively. Our aim was to investigate the role of M2 receptors on the yawning and genital grooming of rats induced by apomorphine, a dopaminergic receptor agonist, focusing on the interaction between cholinergic and dopaminergic pathways. Initially, the effect of atropine, a non-selective muscarinic antagonist, on yawning and genital grooming induced by apomorphine (100 μg/kg s.c.) was analyzed. Atropine doses of 0.5, 1 and 2 mg/kg i.p. were administered to Wistar rats 30 min before induction of the behavioral responses by apomorphine. Number of yawns and time spent genital grooming were quantified over a 60 min period. Apomorphine-induced yawning was increased by low dose (0.5 mg/kg i.p.) but not by high doses (1 and 2 mg/kg, i.p.) of atropine. Genital grooming was antagonized by 2 mg/kg i.p. of atropine and showed no changes at the other doses tested. Tripitramine, a selective M2 cholinergic antagonist, was used as a tool for distinguishing between M2 and all other muscarinic receptor subtypes in yawning and genital grooming. Tripitramine doses of 0.01, 0.02 and 0.04 μmol/kg i.p. were administered to Wistar rats 30 min before apomorphine (100 μg/kg s.c.). Number of yawns and time spent genital grooming were also quantified over a 60 min period. Tripitramine 0.01 μmol/kg increased all parameters. Higher doses, which possibly block all subtypes of muscarinic receptor, did not modify the response of apomorphine, suggesting a non-selective effect of tripitramine at these doses. Given that low doses of tripitramine increased the behavioral responses induced by apomorphine and that the main distribution of the M2

Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

Science.gov (United States)

Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

2011-05-01

Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Activation of muscarinic receptors protects against retinal neurons damage and optic nerve degeneration in vitro and in vivo models.

Science.gov (United States)

Tan, Pan-Pan; Yuan, Hai-Hong; Zhu, Xu; Cui, Yong-Yao; Li, Hui; Feng, Xue-Mei; Qiu, Yu; Chen, Hong-Zhuan; Zhou, Wei

2014-03-01

Muscarinic acetylcholine receptor agonist pilocarpine reduces intraocular pressure (IOP) of glaucoma mainly by stimulating ciliary muscle contraction and then increasing aqueous outflow. It is of our great interest to know whether pilocarpine has the additional properties of retinal neuroprotection independent of IOP lowering in vitro and in vivo models. In rat primary retinal cultures, cell viability was measured using an MTT assay and the trypan blue exclusion method, respectively. Retinal ganglion cells (RGCs) were identified by immunofluorescence and quantified by flow cytometry. For the in vivo study, the retinal damage after retinal ischemia/reperfusion injury in rats was evaluated by histopathological study using hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemical study on cleaved caspase-3, caspase-3, and ChAT. Pretreatment of pilocarpine attenuated glutamate-induced neurotoxicity of primary retinal neurons in a dose-dependent manner. Protection of pilocarpine in both retinal neurons and RGCs was largely abolished by the nonselective muscarinic receptor antagonist atropine and the M1-selective muscarinic receptor antagonist pirenzepine. After ischemia/reperfusion injury in retina, the inner retinal degeneration occurred including ganglion cell layer thinning and neuron lost, and the optic nerve underwent vacuolar changes. These degenerative changes were significantly lessened by topical application of 2% pilocarpine. In addition, the protective effect of pilocarpine on the ischemic rat retina was favorably reflected by downregulating the expression of activated apoptosis marker cleaved caspase-3 and caspase-3 and upregulating the expression of cholinergic cell marker ChAT. Taken together, this highlights pilocarpine through the activation of muscarinic receptors appear to afford significant protection against retinal neurons damage and optic nerve degeneration at clinically relevant concentrations. These data also

Perirhinal Cortex Muscarinic Receptor Blockade Impairs Taste Recognition Memory Formation

OpenAIRE

Gutiérrez, Ranier; De la Cruz, Vanesa; Rodriguez-Ortiz, Carlos J.; Bermudez-Rattoni, Federico

2004-01-01

The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition memory using attenuation of neophobia as an index. In addition, learned taste aversion in both short- and long-term memory tests was exclusively impa...

Photoacoustic microbeam-oscillator with tunable resonance direction and amplitude

Science.gov (United States)

Wu, Qingjun; Li, Fanghao; Wang, Bo; Yi, Futing; Jiang, J. Z.; Zhang, Dongxian

2018-01-01

We successfully design one photoacoustic microbeam-oscillator actuated by nanosecond laser, which exhibits tunable resonance direction and amplitude. The mechanism of laser induced oscillation is systematically analyzed. Both simulation and experimental results reveal that the laser induced acoustic wave propagates in a multi-reflected mode, resulting in resonance in the oscillator. This newly-fabricated micrometer-sized beam-oscillator has an excellent actuation function, i.e., by tuning the laser frequency, the direction and amplitude of actuation can be efficiently altered, which will have potential industrial applications.

Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

Science.gov (United States)

Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

1996-01-01

To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

Synthesis of N-Substituted Piperidine Salts as Potential Muscarinic Ligands for Alzheimer's Applications

Czech Academy of Sciences Publication Activity Database

Boulos, J.; Jakubík, Jan; Randáková, Alena; Avila, C.

2013-01-01

Roč. 50, č. 6 (2013), s. 1363-1367 ISSN 0022-152X R&D Projects: GA ČR(CZ) GA305/09/0681 Institutional support: RVO:67985823 Keywords : N-piperidine substituted salts * muscarinic receptor antagonists * selectivity Subject RIV: ED - Physiology Impact factor: 0.873, year: 2013

Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats.

Science.gov (United States)

Galloway, Claire R; Lebois, Evan P; Shagarabi, Shezza L; Hernandez, Norma A; Manns, Joseph R

2014-01-01

Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.

Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.

Science.gov (United States)

Liang, Zhou; Xin, Wei; Qiang, Liu; Xiang, Cai; Bang-Hua, Liao; Jin, Yang; De-Yi, Luo; Hong, Li; Kun-Jie, Wang

2017-06-01

Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H 2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 μM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO. © 2016 Wiley Periodicals, Inc.

Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Randáková, Alena; Zimčík, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

2017-01-01

Roč. 7, Jan 16 (2017), č. článku 40381. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * N-methylscopolamine * ligand binding * molecular dynamics Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 4.259, year: 2016

Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.

Science.gov (United States)

Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk

2014-04-01

The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.

MUSCARINIC ACETYLCHOLINE RECEPTOR-EXPRESSION IN ASTROCYTES IN THE CORTEX OF YOUNG AND AGED RATS

NARCIS (Netherlands)

VANDERZEE, EA; DEJONG, GI; STROSBERG, AD; LUITEN, PGM

The present report describes the cellular and subcellular distribution pattern of immunoreactivity to M35, a monoclonal antibody raised against purified muscarinic acetylcholine receptor protein, in astrocytes in the cerebral cortex of young and aged rats. Most M35-positive astrocytes were localized

M3 muscarinic receptor interaction with phospholipase C beta3 determines its signaling efficiency

NARCIS (Netherlands)

Kan, W.; Adjobo-Hermans, M.J.; Burroughs, M.; Faibis, G.; Malik, S.; Tall, G.G.; Smrcka, A.V.

2014-01-01

Phospholipase Cbeta (PLCbeta) enzymes are activated by G protein-coupled receptors through receptor-catalyzed guanine nucleotide exchange on Galphabetagamma heterotrimers containing Gq family G proteins. Here we report evidence for a direct interaction between M3 muscarinic receptor (M3R) and

Divergence of allosteric effects of rapacuronium on binding and function of muscarinic receptors

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Randáková, Alena; El-Fakahany, E. E.; Doležal, Vladimír

2009-01-01

Roč. 9, č. 15 (2009), s. 1-20 ISSN 1471-2210 R&D Projects: GA ČR GA305/09/0681; GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic receptors * allosteric modulation * rapacuronium Subject RIV: ED - Physiology

Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease.

Science.gov (United States)

Ztaou, Samira; Maurice, Nicolas; Camon, Jeremy; Guiraudie-Capraz, Gaëlle; Kerkerian-Le Goff, Lydia; Beurrier, Corinne; Liberge, Martine; Amalric, Marianne

2016-08-31

Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect. Muscarinic acetylcholine receptor (mAChR) blockade by scopolamine produces similar anti-parkinsonian effects. To decipher which of the mAChR subtypes provides these beneficial effects, systemic and intrastriatal administration of the selective M1 and M4 mAChR antagonists telenzepine and tropicamide, respectively, were tested in the same model of Parkinson's disease. The two compounds alleviate 6-OHDA lesion-induced motor deficits. Telenzepine produces its beneficial effects by blocking postsynaptic M1 mAChRs expressed on medium spiny neurons (MSNs) at the origin of the indirect striatopallidal and direct striatonigral pathways. The anti-parkinsonian effects of tropicamide were almost completely abolished in mutant lesioned mice that lack M4 mAChRs specifically in dopamine D1-receptor-expressing neurons, suggesting that postsynaptic M4 mAChRs expressed on direct MSNs mediate the antiakinetic action of tropicamide. The present results show that altered cholinergic transmission via M1 and M4 mAChRs of the dorsal striatum plays a pivotal role in the occurrence of motor symptoms in Parkinson's disease. The striatum, where dopaminergic and cholinergic systems interact, is the pivotal structure of basal ganglia involved in pathophysiological changes underlying Parkinson's disease. Here, using optogenetic and pharmacological approaches, we investigated the involvement of striatal

Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber)

DEFF Research Database (Denmark)

Jørgensen, Kristine B.; Krogh-Jensen, Karen; Pickering, Darryl S

2016-01-01

The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1–5 of the naked mole-rat were compared to that of the house mouse (Mus...... musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies...

Visualization of cholinoceptive neurons in the rat neocortex : colocalization of muscarinic and nicotinic acetylcholine receptors

NARCIS (Netherlands)

Zee, E.A. van der; Streefland, C.; Strosberg, A.D.; Schröder, H.; Luiten, P.G.M.

The present investigation analyzes the cellular distribution of muscarinic and nicotinic acetylcholine receptors in rat neocortex, by use of monoclonal antibodies raised against purified receptor proteins. The degree of colocalization of both types of receptors was determined by way of

Endosulfan and cholinergic (muscarinic) transmission: effect on electroencephalograms and [3H]quinuclidinyl benzilate in pigeon brain

International Nuclear Information System (INIS)

Anand, M.; Agrawal, A.K.; Gopal, K.; Sur, R.N.; Seth, P.K.

1986-01-01

Single exposure of endosulfan (5 mg/kg) to pigeons (Columbia livia) caused neuronal hyperexcitability as evidence by spike discharges of 200-500 μV in the electroencephalograms (EEG) from the telencephalon and hyperstriatum, but there was not effect on the ectostriatal area. Cholinergic (muscarinic) receptor binding study using [ 3 H]quinuclidinyl benzilate ([ 3 H]QNB) as a specific ligand indicated that a single exposure to 5 mg/kg of endosulfan caused a significant increase in [ 3 H]QNB binding to the striatal membrane. Behavior study further indicated that a single dose of 200 μg/kg of oxotremorine produced a significant induction in the tremor in endosulfan-pretreated pigeons. The results of this behavioral and biochemical study indicate the involvement of a cholinergic (muscarinic) transmitter system in endosulfan-induced neurotoxicity

Muscarinic M2 receptors directly activate Gq/11 and Gs G-proteins

Czech Academy of Sciences Publication Activity Database

Michal, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

2007-01-01

Roč. 320, č. 2 (2007), s. 607-614 ISSN 0022-3565 R&D Projects: GA ČR GP305/05/P209; GA ČR GA305/05/0452; GA MŠk(CZ) LC554 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic * siRNA * G-proteins Subject RIV: CE - Biochemistry Impact factor: 4.003, year: 2007

Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Ulrik, Charlotte Suppli

2012-01-01

Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel...... long-acting muscarinic antagonist, in patients with COPD....

Onset of effect of aclidinium, a novel, long-acting muscarinic antagonist, in patients with COPD

DEFF Research Database (Denmark)

Vestbo, Jørgen; Vogelmeier, Claus; Creemers, Jacques

2010-01-01

ABSTRACT Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the rate of onset of bronchodilation with aclidinium compared with placebo and tiotropium. This ...

Identification, expression and functional characterization of M4L, a muscarinic acetylcholine M4 receptor splice variant.

Directory of Open Access Journals (Sweden)

Douglas A Schober

Full Text Available Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices. We detected a human upstream exon indicating the translation of the mature longer M4 receptor transcript. The predicted size for the longer two-exon M4 receptor splice variant with the additional 155 amino acid N-terminal extension, designated M4L is 69.7 kDa compared to the 53 kDa canonical single exon M4 receptor (M4S. Western blot analysis from a mammalian overexpression system, and saturation radioligand binding with [3H]-NMS (N-methyl-scopolamine demonstrated the expression of this new splice variant. Comparative pharmacological characterization between the M4L and M4S receptors revealed that both the orthosteric and allosteric binding sites for both receptors were very similar despite the addition of an N-terminal extension.

Identification, expression and functional characterization of M4L, a muscarinic acetylcholine M4 receptor splice variant.

Science.gov (United States)

Schober, Douglas A; Croy, Carrie H; Ruble, Cara L; Tao, Ran; Felder, Christian C

2017-01-01

Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices. We detected a human upstream exon indicating the translation of the mature longer M4 receptor transcript. The predicted size for the longer two-exon M4 receptor splice variant with the additional 155 amino acid N-terminal extension, designated M4L is 69.7 kDa compared to the 53 kDa canonical single exon M4 receptor (M4S). Western blot analysis from a mammalian overexpression system, and saturation radioligand binding with [3H]-NMS (N-methyl-scopolamine) demonstrated the expression of this new splice variant. Comparative pharmacological characterization between the M4L and M4S receptors revealed that both the orthosteric and allosteric binding sites for both receptors were very similar despite the addition of an N-terminal extension.

Z-(-,-)-[76Br]BrQNP: a high affinity PET radiotracer for central and cardiac muscarinic receptors

International Nuclear Information System (INIS)

Strijckmans, V.; Coulon, C.; Loc'h, C.; Maziere, B.; Luo, H.; McPherson, D.W.; Knapp, F.F.

1996-01-01

Racemic E-1-azabicyclo[2.2.2]oct-3-yl α-(1-bromo-1-1-propen-3-yl)-α -hydroxy-α-phenylacetate (BrQNP) was prepared and evaluated in vivo as a potential candidate for imaging muscarinic acetylcholinergic receptors by Positron Emission Tomography. Initial in vivo blocking studies utilizing Z-(-,-)-[ 125 I]IQNP as a radiolabelled muscarinic probe demonstrated that a preinjection of cold E-BrQNP effectively blocks the uptake of the radiolabelled probe in the brain and heart, by 71% and 86% respectively. Z-(-,-)-[ 76 Br]BrQNP was prepared by electrophilic substitution from a tributylstannyl precursor. Peracetic acid and chloramine T was evaluated as oxidizing agents. After purification by SPE and RP-HPLC, radiolabelling yields of 85% and 95% were obtained with peracetic acid and chloramine T, respectively. The final radiochemical yield was 70% for both oxidizing agents. (author)

Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

Science.gov (United States)

Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J

2015-07-01

Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

In vivo and in vitro studies on the potentiation of muscarinic receptor stimulation by alaproclate, a selective 5-HT uptake blocker

International Nuclear Information System (INIS)

Oegren, S.O.; Nordstroem, Oe.; Danielsson, E.; Peterson, L.-L.; Bartfai, T.

1985-01-01

Alaproclate (10-60 mg/kg) injected i.p. into male mice potentiated and prolonged the oxotremorine and physostigmine-induced tremor in a dosedependent manner. Atropine completely blocked the tremor caused by oxotremorine or physostigmine both in the presence and absence of alaproclate. Pretreatment with the 5-HT receptor antagonist metitepine completely blocked the enhancement of oxotremorine-induced tremor caused by alaproclate. Biochemical studies indicated that the above effects cannot be explained by assuming that alaproclate a) acts as a cholinergic agonist, b) inhibits the acetylcholine esterase, c) interferes with choline uptake or acetylcholine synthesis, or d) directly potentiates the release of acetylcholine. In ligand binding studies alaproclate was found to be a weak competitive inhibitor of muscarinic antagonist binding to membranes from the rat cerebral cortex, rat striatum, human cerebral cortex and human striatum. (Ksub(i) approximately 28-40 μM in all four tissues). The present results suggest that alaproclate may potentiate muscarinic responses by a mechanism involving serotonergic receptor mechanisms rather than by a direct interaction with the muscarinic cholinergic receptors. (Author)

In vivo and in vitro studies on the potentiation of muscarinic receptor stimulation by alaproclate, a selective 5-HT uptake blocker

Energy Technology Data Exchange (ETDEWEB)

Oegren, S.O. (Astra Pharmaceuticals AB, Soedertaelje (Sweden)); Nordstroem, Oe.; Danielsson, E.; Peterson, L.L.; Bartfai, T.

1985-01-01

Alaproclate (10-60 mg/kg) injected i.p. into male mice potentiated and prolonged the oxotremorine and physostigmine-induced tremor in a dose dependent manner. Atropine completely blocked the tremor caused by oxotremorine or physostigmine both in the presence and absence of alaproclate. Pretreatment with the 5-HT receptor antagonist metitepine completely blocked the enhancement of oxotremorine-induced tremor caused by alaproclate. Biochemical studies indicated that the above effects cannot be explained by assuming that alaproclate a) acts as a cholinergic agonist, b) inhibits the acetylcholine esterase, c) interferes with choline uptake or acetylcholine synthesis, or d) directly potentiates the release of acetylcholine. In ligand binding studies alaproclate was found to be a weak competitive inhibitor of muscarinic antagonist binding to membranes from the rat cerebral cortex, rat striatum, human cerebral cortex and human striatum. (Ksub(i) approximately 28-40 ..mu..M in all four tissues). The present results suggest that alaproclate may potentiate muscarinic responses by a mechanism involving serotonergic receptor mechanisms rather than by a direct interaction with the muscarinic cholinergic receptors.

Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost-benefit decision making tasks in rats.

Science.gov (United States)

Mendez, Ian A; Gilbert, Ryan J; Bizon, Jennifer L; Setlow, Barry

2012-12-01

Alterations in cost-benefit decision making accompany numerous neuropsychiatric conditions, including schizophrenia, attention deficit hyperactivity disorder, and addiction. Central cholinergic systems have been linked to the etiology and/or treatment of many of these conditions, but little is known about the role of cholinergic signaling in cost-benefit decision making. The goal of these experiments was to determine how cholinergic signaling is involved in cost-benefit decision making, using a behavioral pharmacological approach. Male Long-Evans rats were trained in either "probability discounting" or "delay discounting" tasks, in which rats made discrete-trial choices between a small food reward and a large food reward associated with either varying probabilities of omission or varying delays to delivery, respectively. The effects of acute administration of different doses of nicotinic and muscarinic acetylcholine receptor agonists and antagonists were assessed in each task. In the probability discounting task, acute nicotine administration (1.0 mg/kg) significantly increased choice of the large risky reward, and control experiments suggested that this was due to robust nicotine-induced impairments in behavioral flexibility. In the delay discounting task, the muscarinic antagonists scopolamine (0.03, 0.1, and 0.3 mg/kg) and atropine (0.3 mg/kg) both significantly increased choice of the small immediate reward. Neither mecamylamine nor oxotremorine produced reliable effects on either of the decision making tasks. These data suggest that cholinergic receptors play multiple roles in decision making contexts which include consideration of reward delay or probability. These roles should be considered when targeting these receptors for therapeutic purposes.

Interactions of alaproclate, a selective 5HT-uptake blocker, with muscarinic receptors: in vivo and in vitro studies

International Nuclear Information System (INIS)

Danielsson, E.; Bartfai, T.; Nordstrom, O.; Ogren, S.O.; Unden, A.

1986-01-01

Cholinergic mechanisms play an important role in higher brain functions such as learning or memory. It is hoped that drugs which improve cholinergic transmission would be therapeutically effective in senile dementia. The results of biochemical studies on the interaction of alaproclate with the muscarinic system are summarized. Tritium-4-N-methylpiperidinylbenzilate and methyl tritium-choline chloride were used in the studies. Salivation and hypothermia were studied in adult male mice following injection of alaproclate preceding the injection of oxotremorine by 30 min. Salivation, tremor and hypothermia caused by oxotremorine were found to be centrally mediated muscarinic responses. Tritium-ACh release was studied from synaptosomes. The metabolites of alaproclate, alanine and 2(4 chlorophenyl) 1-1 dimethylethanol, do not produce tremor

Multiple promoters drive tissue-specific expression of the human M2 muscarinic acetylcholine receptor gene

Czech Academy of Sciences Publication Activity Database

Krejčí, Alena; Bruce, A. W.; Doležal, Vladimír; Tuček, Stanislav; Buckley, N. J.

2004-01-01

Roč. 91, č. 1 (2004), s. 88-98 ISSN 0022-3042 R&D Projects: GA AV ČR IAA5011306 Institutional research plan: CEZ:AV0Z5011922 Keywords : M2 muscarinic receptor * neuron-restrictive silence factor * promoter Subject RIV: ED - Physiology Impact factor: 4.824, year: 2004

Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes

Czech Academy of Sciences Publication Activity Database

Boulos, J. F.; Jakubík, Jan; Boulos, J. M.; Randáková, Alena; Momirov, J.

2018-01-01

Roč. 91, č. 1 (2018), s. 93-104 ISSN 1747-0277 R&D Projects: GA ČR(CZ) GA14-05696S; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : G- protein -coupled receptor * muscarinic acetylcholine receptor * N-methylscopolamine * Parkinson's disease * positive allosteric modulator Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.396, year: 2016

Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice

Czech Academy of Sciences Publication Activity Database

Machová, Eva; Jakubík, Jan; Michal, Pavel; Oksman, M.; Iivonen, H.; Tanila, H.; Doležal, Vladimír

2008-01-01

Roč. 29, č. 3 (2008), s. 368-378 ISSN 0197-4580 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA5011206 Grant - others:EC(XE) QLK1-CT-2002-00172 Institutional research plan: CEZ:AV0Z50110509 Keywords : Alzheimer ´s disease * muscarinic receptors * cholinergic neurotransmission Subject RIV: FH - Neurology Impact factor: 5.959, year: 2008

Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms

Czech Academy of Sciences Publication Activity Database

Randáková, Alena; Dolejší, Eva; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; El-Fakahany, E. E.; Jakubík, Jan

2015-01-01

Roč. 97, Jul 2015 (2015), s. 27-39 ISSN 1043-6618 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * atypical agonists * xanomeline * activation mechanism Subject RIV: ED - Physiology Impact factor: 4.816, year: 2015

The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

DEFF Research Database (Denmark)

Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

2003-01-01

Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects ...

An allosteric enhancer of M4muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine

DEFF Research Database (Denmark)

Dencker, Ditte; Weikop, Pia; Sørensen, Gunnar

2012-01-01

The mesostriatal dopamine system plays a key role in mediating the reinforcing effects of psychostimulant drugs like cocaine. The muscarinic M4 acetylcholine receptor subtype is centrally involved in the regulation of dopamine release in striatal areas. Consequently, striatal M4 receptors could...

Speech production in amplitude-modulated noise

DEFF Research Database (Denmark)

Macdonald, Ewen N; Raufer, Stefan

2013-01-01

The Lombard effect refers to the phenomenon where talkers automatically increase their level of speech in a noisy environment. While many studies have characterized how the Lombard effect influences different measures of speech production (e.g., F0, spectral tilt, etc.), few have investigated...... the consequences of temporally fluctuating noise. In the present study, 20 talkers produced speech in a variety of noise conditions, including both steady-state and amplitude-modulated white noise. While listening to noise over headphones, talkers produced randomly generated five word sentences. Similar...... of noisy environments and will alter their speech accordingly....

M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

Science.gov (United States)

Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

2018-03-06

M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

Determinants of positive cooperativity between strychnine-like allosteric modulators and N-methylscopolamine at muscarinic receptors

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Doležal, Vladimír

2006-01-01

Roč. 30, č. 1-2 (2006), s. 111-112 ISSN 0895-8696 R&D Projects: GA ČR(CZ) GA305/05/0452; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic receptors * strychnine -like allosteric modulators * cooperativity Subject RIV: ED - Physiology Impact factor: 2.965, year: 2006

Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost–benefit decision making tasks in rats

Science.gov (United States)

Mendez, Ian A.; Gilbert, Ryan J.; Bizon, Jennifer L.

2012-01-01

Rationale Alterations in cost–benefit decision making accompany numerous neuropsychiatric conditions, including schizophrenia, attention deficit hyperactivity disorder, and addiction. Central cholinergic systems have been linked to the etiology and/or treatment of many of these conditions, but little is known about the role of cholinergic signaling in cost–benefit decision making. Objectives The goal of these experiments was to determine how cholinergic signaling is involved in cost–benefit decision making, using a behavioral pharmacological approach. Methods Male Long-Evans rats were trained in either “probability discounting” or “delay discounting” tasks, in which rats made discrete-trial choices between a small food reward and a large food reward associated with either varying probabilities of omission or varying delays to delivery, respectively. The effects of acute administration of different doses of nicotinic and muscarinic acetylcholine receptor agonists and antagonists were assessed in each task. Results In the probability discounting task, acute nicotine administration (1.0 mg/kg) significantly increased choice of the large risky reward, and control experiments suggested that this was due to robust nicotine-induced impairments in behavioral flexibility. In the delay discounting task, the muscarinic antagonists scopolamine (0.03, 0.1, and 0.3 mg/kg) and atropine (0.3 mg/kg) both significantly increased choice of the small immediate reward. Neither mecamylamine nor oxotremorine produced reliable effects on either of the decision making tasks. Conclusions These data suggest that cholinergic receptors play multiple roles in decision making contexts which include consideration of reward delay or probability. These roles should be considered when targeting these receptors for therapeutic purposes. PMID:22760484

Long-term activation upon brief exposure to xanomleline is unique to M1 and M4 subtypes of muscarinic acetylcholine receptors.

Directory of Open Access Journals (Sweden)

Eva Šantrůčková

Full Text Available Xanomeline is an agonist endowed with functional preference for M1/M4 muscarinic acetylcholine receptors. It also exhibits both reversible and wash-resistant binding to and activation of these receptors. So far the mechanisms of xanomeline selectivity remain unknown. To address this question we employed microfluorometric measurements of intracellular calcium levels and radioligand binding to investigate differences in the short- and long-term effects of xanomeline among muscarinic receptors expressed individually in Chinese hamster ovary cells. 1/One-min exposure of cells to xanomeline markedly increased intracellular calcium at hM1 and hM4, and to a lesser extent at hM2 and hM3 muscarinic receptors for more than 1 hour. 2/Unlike the classic agonists carbachol, oxotremorine, and pilocarpine 10-min exposure to xanomeline did not cause internalization of any receptor subtype. 3/Wash-resistant xanomeline selectively prevented further increase in intracellular calcium by carbachol at hM1 and hM4 receptors. 4/After transient activation xanomeline behaved as a long-term antagonist at hM5 receptors. 5/The antagonist N-methylscopolamine (NMS reversibly blocked activation of hM1 through hM4 receptors by xanomeline. 6/NMS prevented formation of xanomeline wash-resistant binding and activation at hM2 and hM4 receptors and slowed them at hM1, hM3 and hM5 receptors. Our results show commonalities of xanomeline reversible and wash-resistant binding and short-time activation among the five muscarinic receptor subtypes. However long-term receptor activation takes place in full only at hM1 and hM4 receptors. Moreover xanomeline displays higher efficacy at hM1 and hM4 receptors in primary phasic intracellular calcium release. These findings suggest the existence of particular activation mechanisms specific to these two receptors.

Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors.

Science.gov (United States)

Nunes, Eric J; Randall, Patrick A; Podurgiel, Samantha; Correa, Mercè; Salamone, John D

2013-11-01

Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Although nucleus accumbens (NAc) DA depletions or antagonism leave aspects of appetite and primary food motivation intact, rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A2A antagonists can reverse the effects of DA D2 antagonists on effort-related choice, and that stimulation of adenosine A2A receptors produces behavioral effects that are similar to those induced by DA antagonism. The present review summarizes the literature on the role of NAc DA and adenosine in effort-related processes, and also presents original data on the effects of local stimulation of muscarinic acetylcholine receptors in NAc core. Local injections of the muscarinic agonist pilocarpine directly into NAc core produces shifts in effort-related choice behavior similar to those induced by DA antagonism or A2A receptor stimulation, decreasing lever pressing but increasing chow intake in rats responding on a concurrent fixed ratio/chow feeding choice task. In contrast, injections into a neostriatal control site dorsal to the NAc were ineffective. The actions of pilocarpine on this task were attenuated by co-administration of the muscarinic antagonist scopolamine. Thus, drugs that act on DA, adenosine A2A, and muscarinic receptors regulate effort-related choice behavior, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, fatigue or anergia that can be observed in depression and other disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

Activation of multiple G-proteins by muscarinic M1 and M2 receptors

Czech Academy of Sciences Publication Activity Database

Michal, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

2006-01-01

Roč. 27, č. S1 (2006), s. 404-404 ISSN 1671-4083. [World Congress of Pharmacology /15./. 02.07.2006-07.07.2006, Beijing] R&D Projects: GA ČR(CZ) GP305/05/P209; GA ČR(CZ) GA305/05/0452; GA MŠk(CZ) LC554 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic receptors * multiple G-protein coupling Subject RIV: ED - Physiology

Effects of Saw Palmetto Extract on Urodynamic Parameters, Bladder Muscarinic and Purinergic Receptors and Urinary Cytokines in Rats with Cyclophosphamide-Induced Cystitis.

Science.gov (United States)

Nasrin, Sweety; Masuda, Eiji; Kugaya, Haruna; Osano, Ayaka; Ito, Yoshihiko; Yamada, Shizuo

2014-01-01

To clarify the effect of saw palmetto extract (SPE), a phytotherapeutic agent, on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cystitis induced by cyclophosphamide (CYP). Saw palmetto extract (60 mg/kg per day) was administered orally twice a day for 7 days to rats. The urodynamic parameters in CYP (150 mg/kg i.p.)-treated rats were monitored by a cystometric method under anesthesia. The muscarinic and purinergic receptors in the bladder and submaxillary gland were measured by radioreceptor assays using [N-methyl-(3) H] scopolamine chloride([(3) H]NMS) and αβ-methylene-ATP [2,8-(3) H] tetrasodium salt ([(3) H]αβ-MeATP), respectively. Urinary cytokines (interleukin-1β [IL-1β], IL-6 and L-17) were measured with enzyme linked immunosorbent assay kits. Micturition interval and micturition volume were significantly decreased and the frequency of micturition and basal pressure were significantly increased in the CYP-treated rats compared with sham-operated rats. Orally administered SPE significantly increased the micturition interval and micturition volume and decreased the frequency of micturition and basal pressure. The maximal number of sites (Bmax ) for the specific binding of [(3) H]NMS and [(3) H]αβ-MeATP was significantly decreased in the bladder. The decrease in receptors was attenuated by repeated treatment with SPE. An elevation in urinary cytokine (IL-1β and IL-17) levels were seen, and this increase was effectively suppressed by SPE treatment. Saw palmetto extract attenuates the alteration of urodynamic parameters, pharmacologically relevant receptors, and urinary cytokines in CYP-treated rats. Therefore, SPE may be a potential therapeutic agent for improving the clinical symptoms of cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

Role of membrane cholesterol in differential sensitivity of muscarinic receptor subtypes to persistently bound xanomeline

Czech Academy of Sciences Publication Activity Database

Randáková, Alena; Dolejší, Eva; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; El-Fakahany, E. E.; Jakubík, Jan

2018-01-01

Roč. 133, May 1 (2018), s. 129-144 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA14-05696S; GA ČR(CZ) GA17-16182S Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * membrane cholesterol * xanomeline * receptor activation * molecular dynamics Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 5.012, year: 2016

Uncoupling of M1 muscarinic receptor/G-protein interaction by amyloid beta(1-42)

Czech Academy of Sciences Publication Activity Database

Janíčková, Helena; Rudajev, Vladimír; Zimčík, Pavel; Jakubík, Jan; Tanila, H.; El-Fakahany, E. E.; Doležal, Vladimír

2013-01-01

Roč. 67, April (2013), s. 272-283 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) 7E10060 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : Alzheimer ´s Disease * muscarinic receptors * G-proteins Subject RIV: ED - Physiology Impact factor: 4.819, year: 2013

Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care.

Science.gov (United States)

Bennett, Mike; Lucas, Viv; Brennan, Mary; Hughes, Andrew; O'Donnell, Valerie; Wee, Bee

2002-09-01

The management of 'death rattle' was reviewed by a task group on behalf of the Association for Palliative Medicine's Science Committee. Evidence was searched for the effectiveness of various anti-muscarinic drugs in drying oropharyngeal and bronchial secretions in dying patients. Clinical guidelines were constructed based on evidence from volunteer and clinical studies. Death rattle occurs in half of all dying patients and some response occurs in around 80% of treated patients. Clinical studies demonstrate that subcutaneous hyoscine hydrobromide 400 microg is more effective at improving symptoms at 30 min than glycopyrronium 200 microg by the same route. Volunteer studies demonstrate that intramuscular glycopyrronium 400 microg is as effective in drying secretions at 30 min as a dose of 200 microg given intravenously. Duration of response is shortest for hyoscine butylbromide (1 h) and longest for glycopyrronium (more than 6 h). There is insufficient evidence to support the use of one drug over another in a continuous infusion and prescribers should base decisions on different characteristics of each anti-muscarinic drug.

The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection.

Directory of Open Access Journals (Sweden)

Matthew Darby

2015-01-01

Full Text Available Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection.

Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases.

Science.gov (United States)

Felder, Christian C; Goldsmith, Paul J; Jackson, Kimberley; Sanger, Helen E; Evans, David A; Mogg, Adrian J; Broad, Lisa M

2018-01-25

The cholinergic signalling system has been an attractive pathway to seek targets for modulation of arousal, cognition, and attention which are compromised in neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic receptor M1 and M4 subtypes which are highly expressed in the central nervous system, in cortex, hippocampus and striatum, key areas of cognitive and neuropsychiatric control, have received particular attention. Historical muscarinic drug development yielded first generation agonists with modest selectivity for these two receptor targets over M2 and M3 receptors, the major peripheral sub-types hypothesised to underlie the dose-limiting clinical side effects. More recent compound screening and medicinal chemistry optimization of orthosteric and allosteric agonists, and positive allosteric modulators binding to sites distinct from the highly homologous acetylcholine binding pocket have yielded a collection of highly selective tool compounds for preclinical validation studies. Several M1 selective ligands have progressed to early clinical development and in time will hopefully lead to useful therapeutics for treating symptoms of Alzheimer's disease and related disorders. Copyright © 2018. Published by Elsevier Ltd.

Muscarinic receptors in separate populations of noradrenaline- and adrenaline-containing chromaffin cells

International Nuclear Information System (INIS)

Michelena, P.; Moro, M.A.; Castillo, C.J.; Garcia, A.G.

1991-01-01

We have performed binding experiments of (a)[3H]quinuclidinyl benzilate to partially purified membranes from noradrenaline- and adrenaline-containing chromaffin cells and (b) [3H]N-methyl-quinuclidinyl benzilate to acutely isolated, or 48-h cultured, chromaffin cells subpopulations. Using this approach, we obtained enough evidence to conclude (1st) that muscarinic receptors are present in both noradrenaline- and adrenaline containing cells; (2nd) that noradrenaline cells contain in fact 2-3 fold higher density of those receptors; and (3rd) that those receptors undergo plastic changes upon chronic culturing of the cells

The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography

International Nuclear Information System (INIS)

Weinberger, D.R.; Gibson, R.; Coppola, R.; Jones, D.W.; Molchan, S.; Sunderland, T.; Berman, K.F.; Reba, R.C.

1991-01-01

A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification

Muscarinic receptors as targets for anti-inflammatory therapy.

Science.gov (United States)

Sales, María Elena

2010-11-01

ACh, the main neurotransmitter in the neuronal cholinergic system, is synthesized by pre-ganglionic fibers of the sympathetic and parasympathetic autonomic nervous system and by post-ganglionic parasympathetic fibers. There is increasing experimental evidence that ACh is widely expressed in prokaryotic and eukaryotic non-neuronal cells. The neuronal and non-neuronal cholinergic systems comprise ACh, choline acetyltransferase and cholinesterase, enzymes that synthesize and catabolize ACh, and the nicotinic and muscarinic ACh receptors (nAChRs and mAChRs, respectively), which are the targets for ACh action. This review analyzes the participation of the cholinergic system, particularly through mAChRs, in inflammation, and discusses the role of the different mAChR antagonists that have been used to treat skin inflammatory disorders, asthma and COPD, as well as intestinal inflammation and systemic inflammatory diseases, to assess the potential application of these compounds as therapeutic tools.

Differentiation-associated decrease in muscarinic receptor sensitivity in human neuroblastoma cells

International Nuclear Information System (INIS)

Heikkilae, J.E.; Scott, J.G.; Suominen, L.A.; Akerman, K.E.O.

1987-01-01

Muscarinic receptor-linked increases in intracellular free Ca 2+ as measured with quin-2 and Ca 2+ release from monolayers of cells have been measured in the human neuroblastoma cell line SH-SY5Y. Induction of differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to a decrease in the sensitivity of the cells to low concentrations of agonists with respect to the induced increase in cytosolic free Ca 2+ and stimulation of Ca 2+ efflux. No decrease in agonist binding affinity was observed when the displacement of a labelled antagonist, 3 H-NMS, by a non-labelled agonist was studied

The detection of the non-M2 muscarinic receptor subtype in the rat heart atria and ventricles

Czech Academy of Sciences Publication Activity Database

Mysliveček, J.; Klein, M.; Nováková, M.; Říčný, Jan

2008-01-01

Roč. 378, č. 1 (2008), s. 103-116 ISSN 0028-1298 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA304/08/0256 Institutional research plan: CEZ:AV0Z50110509 Keywords : heart * muscarinic receptors * PLC activity Subject RIV: FH - Neuro logy Impact factor: 2.830, year: 2008

Color guided amplitudes

Energy Technology Data Exchange (ETDEWEB)

Broedel, Johannes [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University, Stanford, CA (United States); Dixon, Lance J. [SLAC National Accelerator Laboratory, Stanford University, Stanford, CA (United States)

2012-07-01

Amplitudes in gauge thoeries obtain contributions from color and kinematics. While these two parts of the amplitude seem to exhibit different symmetry structures, it turns out that they can be reorganized in a way to behave equally, which leads to the so-called color-kinematic dual representations of amplitudes. Astonishingly, the existence of those representations allows squaring to related gravitational theories right away. Contrary to the Kawaii-Levellen-Tye relations, which have been used to relate gauge theories and gravity previously, this method is applicable not only to tree amplitudes but also at loop level. In this talk, the basic technique is introduced followed by a discussion of the existence of color-kinematic dual representations for amplitudes derived from gauge theory actions which are deformed by higher-operator insertions. In addition, it is commented on the implications for deformed gravitational theories.

Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication

Directory of Open Access Journals (Sweden)

E. Roda

2016-01-01

Full Text Available Introduction. Chronic poisoning may result in home setting after mercury (Hg vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg monitoring were performed from admission (t0, until 1 year later (t2, paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs. At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1–4.5; UHg 0.1–4.5, associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0–16.0. At t1 (two days after DMSA-mobilization test, BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes. At t2 (eight months after two cycles of DMSA chelating therapy ending, gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp. and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes. Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

The acetylcholinesterase inhibitor galantamine inhibits d-amphetamine-induced psychotic-like behavior in Cebus monkeys

DEFF Research Database (Denmark)

Andersen, Maibritt B; Werge, Thomas; Fink-Jensen, Anders

2007-01-01

Cholinergic receptors (AChR) are reported altered in brains from schizophrenic patients, and a growing body of evidence suggests that muscarinic receptor agonists exhibit antipsychotic potential. Centrally acting selective muscarinic receptor agonists are currently not available for clinical use,...

Involvement of Ca2+ Signaling in the Synergistic Effects between Muscarinic Receptor Antagonists and β2-Adrenoceptor Agonists in Airway Smooth Muscle

Directory of Open Access Journals (Sweden)

Kentaro Fukunaga

2016-09-01

Full Text Available Long-acting muscarinic antagonists (LAMAs and short-acting β2-adrenoceptor agonists (SABAs play important roles in remedy for COPD. To propel a translational research for development of bronchodilator therapy, synergistic effects between SABAs with LAMAs were examined focused on Ca2+ signaling using simultaneous records of isometric tension and F340/F380 in fura-2-loaded tracheal smooth muscle. Glycopyrronium (3 nM, a LAMA, modestly reduced methacholine (1 μM-induced contraction. When procaterol, salbutamol and SABAs were applied in the presence of glycopyrronium, relaxant effects of these SABAs are markedly enhanced, and percent inhibition of tension was much greater than the sum of those for each agent and those expected from the BI theory. In contrast, percent inhibition of F340/F380 was not greater than those values. Bisindolylmaleimide, an inhibitor of protein kinase C (PKC, significantly increased the relaxant effect of LAMA without reducing F340/F380. Iberiotoxin, an inhibitor of large-conductance Ca2+-activated K+ (KCa channels, significantly suppressed the effects of these combined agents with reducing F340/F380. In conclusion, combination of SABAs with LAMAs synergistically enhances inhibition of muscarinic contraction via decreasing both Ca2+ sensitization mediated by PKC and Ca2+ dynamics mediated by KCa channels. PKC and KCa channels may be molecular targets for cross talk between β2-adrenoceptors and muscarinic receptors.

ALTERATIONS IN ELECTROCARDIOGRAMS OF LABRADOR RETRIEVER DOGS DURING HANDLING WITH AND WITHOUT GLOVES

Directory of Open Access Journals (Sweden)

Swagat Mohapatra

2016-12-01

Full Text Available Healthy male Labrador Retriever dogs (n=8 aged between one to three years constituted the study material. The study was carried out to peruse the alterations in electrocardiograms, when the attendant restrained the dogs with bare hands and when the dogs were restrained by the attendant wearing gloves. The mean amplitude of P wave was higher in dogs handled with gloves. Similarly, the amplitudes of QRS complex and T wave were higher in the electrocardiograms of dogs handled with insulated hands. Meanwhile, the duration of T wave and Q-T interval were higher in the electrocardiograms recorded without gloves in hands. However, no alterations were perceived with respect to the duration of P wave, duration of T wave, the P-R interval, R-R interval and the heart rate. Except for the amplitude of P wave, no other differences were statistically significant. The study reported the alterations in the electrocardiogram while handling the animals with bare hands.

Immunocytochemical demonstration of M1 muscarinic acetylcholine receptors at the presynaptic and postsynaptic membranes of rat diaphragm endplates

Czech Academy of Sciences Publication Activity Database

Malomouzh, A. I.; Arkhipova, S. S.; Nikolsky, E. E.; Vyskočil, František

2011-01-01

Roč. 60, č. 1 (2011), s. 185-188 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110905; GA ČR GA202/09/0806 Institutional research plan: CEZ:AV0Z50110509 Keywords : skeletal muscle * M1 muscarinic receptor Subject RIV: ED - Physiology Impact factor: 1.555, year: 2011

Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides as potent and long acting muscarinic antagonists.

Science.gov (United States)

Prat, Maria; Buil, María Antonia; Fernández, Maria Dolors; Tort, Laia; Monleón, Juan Manuel; Casals, Gaspar; Ferrer, Manuel; Castro, Jordi; Gavaldà, Amadeu; Miralpeix, Montserrat; Ramos, Israel; Vilella, Dolors; Huerta, Josep Maria; Espinosa, Sònia; Hernández, Begoña; Segarra, Victor; Córdoba, Mònica

2015-04-15

Novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides have been identified as potent M3 muscarinic antagonists with a long duration of action in an in vivo model of bronchoconstriction. The synthesis, structure-activity relationships and biological evaluation of this series of compounds are reported. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lipid-Based Diets Improve Muscarinic Neurotransmission in the Hippocampus of Transgenic APPswe/PS1dE9 Mice

Czech Academy of Sciences Publication Activity Database

Janíčková, Helena; Rudajev, Vladimír; Dolejší, Eva; Koivisto, H.; Jakubík, Jan; Tanila, H.; El-Fakahany, E. E.; Doležal, Vladimír

2015-01-01

Roč. 12, č. 10 (2015), s. 923-931 ISSN 1567-2050 R&D Projects: GA MŠk(CZ) 7E10060; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : G-protein activation * hippocampus * muscarinic neurotransmission * nutrition * omega-3 fatty acids * stigmasterol Subject RIV: FH - Neurology Impact factor: 3.145, year: 2015

The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

Science.gov (United States)

Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

2015-01-01

We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Two-Loop Splitting Amplitudes

International Nuclear Information System (INIS)

Bern, Z.

2004-01-01

Splitting amplitudes govern the behavior of scattering amplitudes at the momenta of external legs become collinear. In this talk we outline the calculation of two-loop splitting amplitudes via the unitarity sewing method. This method retains the simple factorization properties of light-cone gauge, but avoids the need for prescriptions such as the principal value or Mandelstam-Leibbrandt ones. The encountered loop momentum integrals are then evaluated using integration-by-parts and Lorentz invariance identities. We outline a variety of applications for these splitting amplitudes

Two-loop splitting amplitudes

International Nuclear Information System (INIS)

Bern, Z.; Dixon, L.J.; Kosower, D.A.

2004-01-01

Splitting amplitudes govern the behavior of scattering amplitudes at the momenta of external legs become collinear. In this talk we outline the calculation of two-loop splitting amplitudes via the unitarity sewing method. This method retains the simple factorization properties of light-cone gauge, but avoids the need for prescriptions such as the principal value or Mandelstam-Leibbrandt ones. The encountered loop momentum integrals are then evaluated using integration-by-parts and Lorentz invariance identities. We outline a variety of applications for these splitting amplitudes

A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells.

Science.gov (United States)

Pelissier-Rota, M; Chartier, N T; Bonaz, B; Jacquier-Sarlin, M R

2017-07-01

Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction. Non-neuronal acetylcholine (Ach) and muscarinic receptors (mAchR) also contribute to alterations of epithelial cell functions. In this study, we investigated the mechanisms through which stress and Ach modulate epithelial cell adhesive properties. We show that Ach-induced activation of mAchR in HT-29 cells results in cell dissociation together with changes in cell-matrix contacts, which correlates with the acquisition of invasive potential consistent with a matrix metalloproteinase (MMP) mode of invasion. These processes result from mAchR subsequent stimulation of the cascade of src/Erk and FAK activation. Ach-induced secretion of laminin 332 leads to α3β1 integrin activation and RhoA-dependent reorganization of the actin cytoskeleton. We show that Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling. This is reinforced by the fact that Ach-mediated activation of mAchR stimulates both the synthesis and the release of CRF2 ligands in HT-29 cells (effects blocked by atropine). In summary, our data provides evidence for a novel intracellular circuit involving mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier dysfunction and exacerbate mucosal inflammation. Copyright © 2017. Published by Elsevier B.V.

Characterization of the effect of penehyclidine hydrochloride on muscarinic receptor subtypes mediating the contraction of guinea-pig isolated gastrointestinal smooth muscle.

Science.gov (United States)

Xiao, Hong-Tao; Liao, Zhi; Meng, Xian-Min; Yan, Xiao-Yan; Chen, Shu-Jie; Mo, Zheng-Ji

2009-07-01

The aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea-pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes. Radioimmune assay was used to determine cAMP levels in isolated guinea-pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes. The results indicated that the relaxing effect of penehyclidine hydrochloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA2 values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig stomach smooth muscle and decreased the cAMP content in isolated guinea-pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 mumol/l. The results suggest that penehyclidine hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig gastrointestinal smooth muscle.

Amplitudes, acquisition and imaging

Energy Technology Data Exchange (ETDEWEB)

Bloor, Robert

1998-12-31

Accurate seismic amplitude information is important for the successful evaluation of many prospects and the importance of such amplitude information is increasing with the advent of time lapse seismic techniques. It is now widely accepted that the proper treatment of amplitudes requires seismic imaging in the form of either time or depth migration. A key factor in seismic imaging is the spatial sampling of the data and its relationship to the imaging algorithms. This presentation demonstrates that acquisition caused spatial sampling irregularity can affect the seismic imaging and perturb amplitudes. Equalization helps to balance the amplitudes, and the dealing strategy improves the imaging further when there are azimuth variations. Equalization and dealiasing can also help with the acquisition irregularities caused by shot and receiver dislocation or missing traces. 2 refs., 2 figs.

The effects of nicotinic and muscarinic receptor activation on patch-clamped cells in the optic tectum of Rana pipiens.

Science.gov (United States)

Yu, C-J; Debski, E A

2003-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 microM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) and bicuculline (25 microM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 microM). Muscarinic receptor-mediated responses, induced by carbachol (100 microM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input.

Association between pain episodes and high amplitude propagated pressure waves in patients with irritable bowel syndrome

NARCIS (Netherlands)

Clemens, C. H. M.; Samsom, M.; Roelofs, J. M. M.; van Berge Henegouwen, G. P.; Smout, A. J. P. M.

2003-01-01

OBJECTIVES: In the pathogenesis of irritable bowel syndrome (IBS), both increased visceral sensitivity and altered colonic motility seem to play a role. The aim of this study was to quantify the temporal relationship between pain episodes and the occurrence of high amplitude propagated pressure

Relative amplitude preservation processing utilizing surface consistent amplitude correction. Part 4; Surface consistent amplitude correction wo mochiita sotai shinpuku hozon shori. 4

Energy Technology Data Exchange (ETDEWEB)

Saeki, T [Japan National Oil Corp., Tokyo (Japan). Technology Research Center

1997-10-22

Discussions were given on seismic exploration from the ground surface using the reflection method, for surface consistent amplitude correction from among effects imposed from the ground surface and a surface layer. Amplitude distribution on the reflection wave zone is complex. Therefore, items to be considered in making an analysis are multiple, such as estimation of spherical surface divergence effect and exponential attenuation effect, not only amplitude change through the surface layer. If all of these items are taken into consideration, burden of the work becomes excessive. As a method to solve this problem, utilization of amplitude in initial movement of a diffraction wave may be conceived. Distribution of the amplitude in initial movement of the diffraction wave shows a value relatively close to distribution of the vibration transmitting and receiving points. The reason for this is thought because characteristics of the vibration transmitting and receiving points related with waveline paths in the vicinity of the ground surface have no great difference both on the diffraction waves and on the reflection waves. The lecture described in this paper introduces an attempt of improving the efficiency of the surface consistent amplitude correction by utilizing the analysis of amplitude in initial movement of the diffraction wave. 4 refs., 2 figs.

Brain cortex muscarinic transmission is impaired in young adult transgenic Appswe/Ps1de9 female mice

Czech Academy of Sciences Publication Activity Database

Machová, Eva; Jakubík, Jan; Michal, Pavel; Oksman, M.; Iivonen, H.; Tanila, H.; Doležal, Vladimír

2007-01-01

Roč. 4, Suppl.1 (2007), s. 281-281 ISSN 1660-2854. [International conference Alzheimer ´s diseases/Parkinson´s diseases /8./. 14.03.2007-18.03.2007, Salzburg] R&D Projects: GA AV ČR(CZ) IAA5011206; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpr1 * brain cortex * muscarinic transmission * Alzheimer ´s disease Subject RIV: FH - Neurology

Reproductive cycles in tropical intertidal gastropods are timed around tidal amplitude cycles.

Science.gov (United States)

Collin, Rachel; Kerr, Kecia; Contolini, Gina; Ochoa, Isis

2017-08-01

Reproduction in iteroparous marine organisms is often timed with abiotic cycles and may follow lunar, tidal amplitude, or daily cycles. Among intertidal marine invertebrates, decapods are well known to time larval release to coincide with large amplitude nighttime tides, which minimizes the risk of predation. Such bimonthly cycles have been reported for few other intertidal invertebrates. We documented the reproduction of 6 gastropod species from Panama to determine whether they demonstrate reproductive cycles, whether these cycles follow a 2-week cycle, and whether cycles are timed so that larval release occurs during large amplitude tides. Two of the species ( Crepidula cf. marginalis and Nerita scabricosta ) showed nonuniform reproduction, but without clear peaks in timing relative to tidal or lunar cycles. The other 4 species show clear peaks in reproduction occurring every 2 weeks. In 3 of these species ( Cerithideopsis carlifornica var. valida, Littoraria variegata , and Natica chemnitzi ), hatching occurred within 4 days of the maximum amplitude tides. Siphonaria palmata exhibit strong cycles, but reproduction occurred during the neap tides. Strong differences in the intensity of reproduction of Cerithideopsis carlifornica , and in particular, Littoraria variegata , between the larger and smaller spring tides of a lunar month indicate that these species time reproduction with the tidal amplitude cycle rather than the lunar cycle. For those species that reproduce during both the wet and dry seasons, we found that reproductive timing did not differ between seasons despite strong differences in temperature and precipitation. Overall, we found that most (4/6) species have strong reproductive cycles synchronized with the tidal amplitude cycle and that seasonal differences in abiotic factors do not alter these cycles.

Molecular basis of the functional heterogeneity of the muscarinic acetylcholine receptor

International Nuclear Information System (INIS)

Numa, S.; Fukuda, K.; Kubo, T.; Maeda, A.; Akiba, I.; Bujo, H.; Nakai, J.; Mishina, M.; Higashida, H.

1988-01-01

The muscarinic acetylcholine receptor (mAChR) mediates a variety of cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides, and modulation of potassium channels, through the action of guanine-nucleotide-binding regulatory proteins (G proteins). The question then arises as to whether multiple mAChR species exist that are responsible for the various biochemical and physiological effects. In fact, pharmacologically distinguishable forms of the mAChR occur in different tissues and have been provisionally classified into M 1 (I), M 2 cardiac (II), and M 2 glandular (III) subtypes on the basis of their difference in apparent affinity for antagonists. Here, the authors have made attempts to understand the molecular basis of the functional heterogeneity of the mAChR, using recombinant DNA technology

Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

International Nuclear Information System (INIS)

Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

1988-01-01

Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of 3 H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity

Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

Energy Technology Data Exchange (ETDEWEB)

Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

1988-01-01

Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of /sup 3/H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity.

Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

Science.gov (United States)

Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen

2009-04-14

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

Movement amplitude on the Functional Re-adaptive Exercise Device: deep spinal muscle activity and movement control.

Science.gov (United States)

Winnard, A; Debuse, D; Wilkinson, M; Samson, L; Weber, T; Caplan, Nick

2017-08-01

Lumbar multifidus (LM) and transversus abdominis (TrA) show altered motor control, and LM is atrophied, in people with low-back pain (LBP). The Functional Re-adaptive Exercise Device (FRED) involves cyclical lower-limb movement against minimal resistance in an upright posture. It has been shown to recruit LM and TrA automatically, and may have potential as an intervention for non-specific LBP. However, no studies have yet investigated the effects of changes in FRED movement amplitude on the activity of these muscles. This study aimed to assess the effects of different FRED movement amplitudes on LM and TrA muscle thickness and movement variability, to inform an evidence-based exercise prescription. Lumbar multifidus and TrA thickness of eight healthy male volunteers were examined using ultrasound imaging during FRED exercise, normalised to rest at four different movement amplitudes. Movement variability was also measured. Magnitude-based inferences were used to compare each amplitude. Exercise at all amplitudes recruited LM and TrA more than rest, with thickness increases of approximately 5 and 1 mm, respectively. Larger amplitudes also caused increased TrA thickness, LM and TrA muscle thickness variability and movement variability. The data suggests that all amplitudes are useful for recruiting LM and TrA. A progressive training protocol should start in the smallest amplitude, increasing the setting once participants can maintain a consistent movement speed, to continue to challenge the motor control system.

Diphoton generalized distribution amplitudes

International Nuclear Information System (INIS)

El Beiyad, M.; Pire, B.; Szymanowski, L.; Wallon, S.

2008-01-01

We calculate the leading order diphoton generalized distribution amplitudes by calculating the amplitude of the process γ*γ→γγ in the low energy and high photon virtuality region at the Born order and in the leading logarithmic approximation. As in the case of the anomalous photon structure functions, the γγ generalized distribution amplitudes exhibit a characteristic lnQ 2 behavior and obey inhomogeneous QCD evolution equations.

Analyticity properties of two-body helicity amplitudes; Proprietes d'analyticite des amplitudes d'helicite a deux corps

Energy Technology Data Exchange (ETDEWEB)

Navelet-Noualhier, H [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1967-06-15

Helicity amplitudes are expressed via the spinor amplitudes in terms of the Joos invariant which have been shown by Williams to be free from kinematical singularities. This procedure allows to analyze the kinematical singularities of helicity amplitudes and separate them out, which results into the definition of regularized helicity amplitudes. A crossing matrix for helicity amplitudes, is written down, corresponding to the continuation path used to cross spinor amplitudes. We verify explicitly that the corresponding crossing matrix for regularized helicity amplitudes is uniform as it should be. Kinematical constraints which generalize, to the case of arbitrary spins and masses, relations which must hold between helicity amplitudes at some values of the energy variable in {pi}N {yields} {pi}N, {pi}{pi} {yields} NN-bar and NN-bar {yields} NN-bar reactions, appear as a consequence of the existence of poles in the crossing matrix between regularized helicity amplitudes. An english version of this work has been written with G. Cohen-Tannoudji and A. Morel and submitted for publication to Annals of Physics. (author) [French] Les amplitudes d'helicite pour une reaction a deux corps sont exprimees, par l'intermediaire des amplitudes spinorielles, en fonction d'amplitudes invariantes de Joos qui sont, comme l'a montre Williams, sans singularites cinematiques. Ce procede nous permet d'analyser puis d'eliminer les singularites cinematiques des amplitudes d'helicite. Ceci nous conduit a la definition d'amplitudes d'helicite 'regularisees'. Une relation de 'croisement' entre amplitudes d'helicite est ecrite; elle realise leur prolongement analytique le long du chemin utilise pour 'croiser' les amplitudes spinorielles. Nous verifions que les elements de la matrice de croisement entre amplitudes d'helicite 'regularisees' sont bien uniformes. Les contraintes cinematiques qui generalisent, au cas de masses et de spins arbitraires, les relations obtenues dans les reactions {pi

Real topological string amplitudes

Energy Technology Data Exchange (ETDEWEB)

Narain, K.S. [The Abdus Salam International Centre for Theoretical Physics (ICTP),Strada Costiera 11, Trieste, 34151 (Italy); Piazzalunga, N. [Simons Center for Geometry and Physics, State University of New York,Stony Brook, NY, 11794-3636 (United States); International School for Advanced Studies (SISSA) and INFN, Sez. di Trieste,via Bonomea 265, Trieste, 34136 (Italy); Tanzini, A. [International School for Advanced Studies (SISSA) and INFN, Sez. di Trieste,via Bonomea 265, Trieste, 34136 (Italy)

2017-03-15

We discuss the physical superstring correlation functions in type I theory (or equivalently type II with orientifold) that compute real topological string amplitudes. We consider the correlator corresponding to holomorphic derivative of the real topological amplitude G{sub χ}, at fixed worldsheet Euler characteristic χ. This corresponds in the low-energy effective action to N=2 Weyl multiplet, appropriately reduced to the orientifold invariant part, and raised to the power g{sup ′}=−χ+1. We show that the physical string correlator gives precisely the holomorphic derivative of topological amplitude. Finally, we apply this method to the standard closed oriented case as well, and prove a similar statement for the topological amplitude F{sub g}.

Costimulation of N-methyl-d-aspartate and muscarinic neuronal receptors modulates gap junctional communication in striatal astrocytes

OpenAIRE

Rouach, N.; Tencé, M.; Glowinski, J.; Giaume, C.

2002-01-01

Cocultures of neurons and astrocytes from the rat striatum were used to determine whether the stimulation of neuronal receptors could affect the level of intercellular communication mediated by gap junctions in astrocytes. The costimulation of N-methyl-D-asparte (NMDA) and muscarinic receptors led to a prominent reduction of astrocyte gap junctional communication (GJC) in coculture. This treatment was not effective in astrocyte cultures, these cells being devoid of NMDA receptors. Both types ...

Slow oscillation amplitudes and up-state lengths relate to memory improvement.

Directory of Open Access Journals (Sweden)

Dominik P J Heib

Full Text Available There is growing evidence of the active involvement of sleep in memory consolidation. Besides hippocampal sharp wave-ripple complexes and sleep spindles, slow oscillations appear to play a key role in the process of sleep-associated memory consolidation. Furthermore, slow oscillation amplitude and spectral power increase during the night after learning declarative and procedural memory tasks. However, it is unresolved whether learning-induced changes specifically alter characteristics of individual slow oscillations, such as the slow oscillation up-state length and amplitude, which are believed to be important for neuronal replay. 24 subjects (12 men aged between 20 and 30 years participated in a randomized, within-subject, multicenter study. Subjects slept on three occasions for a whole night in the sleep laboratory with full polysomnography. Whereas the first night only served for adaptation purposes, the two remaining nights were preceded by a declarative word-pair task or by a non-learning control task. Slow oscillations were detected in non-rapid eye movement sleep over electrode Fz. Results indicate positive correlations between the length of the up-state as well as the amplitude of both slow oscillation phases and changes in memory performance from pre to post sleep. We speculate that the prolonged slow oscillation up-state length might extend the timeframe for the transfer of initial hippocampal to long-term cortical memory representations, whereas the increase in slow oscillation amplitudes possibly reflects changes in the net synaptic strength of cortical networks.

Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Tuček, Stanislav; El-Fakahany, E. E.

2002-01-01

Roč. 301, č. 3 (2002), s. 1033-1041 ISSN 0022-3565 R&D Projects: GA ČR GP305/01/D119 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z5011922 Keywords : xanomeline * M(1) muscarinic acetylcholine receptor Subject RIV: FH - Neurology Impact factor: 3.991, year: 2002

Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.

Science.gov (United States)

Sakkal, Leon A; Rajkowski, Kyle Z; Armen, Roger S

2017-06-05

Following insights from recent crystal structures of the muscarinic acetylcholine receptor, binding modes of Positive Allosteric Modulators (PAMs) were predicted under the assumption that PAMs should bind to the extracellular surface of the active state. A series of well-characterized PAMs for adenosine (A 1 R, A 2A R, A 3 R) and muscarinic acetylcholine (M 1 R, M 5 R) receptors were modeled using both rigid and flexible receptor CHARMM-based molecular docking. Studies of adenosine receptors investigated the molecular basis of the probe-dependence of PAM activity by modeling in complex with specific agonist radioligands. Consensus binding modes map common pharmacophore features of several chemical series to specific binding interactions. These models provide a rationalization of how PAM binding slows agonist radioligand dissociation kinetics. M 1 R PAMs were predicted to bind in the analogous M 2 R PAM LY2119620 binding site. The M 5 R NAM (ML-375) was predicted to bind in the PAM (ML-380) binding site with a unique induced-fit receptor conformation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Unifying relations for scattering amplitudes

Science.gov (United States)

Cheung, Clifford; Shen, Chia-Hsien; Wen, Congkao

2018-02-01

We derive new amplitudes relations revealing a hidden unity among a wideranging variety of theories in arbitrary spacetime dimensions. Our results rely on a set of Lorentz invariant differential operators which transmute physical tree-level scattering amplitudes into new ones. By transmuting the amplitudes of gravity coupled to a dilaton and two-form, we generate all the amplitudes of Einstein-Yang-Mills theory, Dirac-Born-Infield theory, special Galileon, nonlinear sigma model, and biadjoint scalar theory. Transmutation also relates amplitudes in string theory and its variants. As a corollary, celebrated aspects of gluon and graviton scattering like color-kinematics duality, the KLT relations, and the CHY construction are inherited traits of the transmuted amplitudes. Transmutation recasts the Adler zero as a trivial consequence of the Weinberg soft theorem and implies new subleading soft theorems for certain scalar theories.

Muscarinic receptor binding increases in anterior thalamus and cingulate cortex during discriminative avoidance learning

International Nuclear Information System (INIS)

Vogt, B.A.; Gabriel, M.; Vogt, L.J.; Poremba, A.; Jensen, E.L.; Kubota, Y.; Kang, E.

1991-01-01

Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OxO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OxO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OxO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OxO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OxO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OxO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OxO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated

Pulse-amplitude multipliers using logarithmic amplitude-to-time conversion; Amplificateurs d'impulsions utilisant une conversion logarithmique temps-amplitude; Ob umnozhitelyakh amplitudy impul'sov s ispol'zovaniem logarifmicheskogo preobrazovaniya amplitudy vo vremya; Multiplicadores de amplitud de impulso usando una conversion logaritmica de amplitud en tiempo

Energy Technology Data Exchange (ETDEWEB)

Konrad, M [Institut Rudjer Boskovic, Zagreb, Yugoslavia (Croatia)

1962-04-15

The accuracy and limitations of multipliers based on logarithmic amplitude-to-time conversion using RC pulse stretchers are discussed with respect to their application for determining whether the amplitude product of two coincident pulses has a given value. Some possible circuits are given. (author) [French] L'auteur etudie la precision et les limitations des amplificateurs fondes sur la conversion logarithmique temps-amplitude et utilisant des allongeurs d'impulsions RC, afin d'etablir si ces appareils peuvent servir a determiner la valeur du produit des amplitudes de deux impulsions coincidentes. Il decrit en outre plusieurs circuits possibles. (author) [Spanish] La memoria discute la precision y limitaciones de los multiplicadores basados en la conversion logaritmica de amplitud en tiempo empleando circuitos alargadores de resistencia-capacidad en relacion con su aplicacion para determinar si el producto de las amplitudes de dos impulsos coincidentes tiene un valor determinado. Indica algunos circuitos posibles. (author) [Russian] Obsuzhdayutsya predel pogreshnosti i ogranicheniya umnozhitelej, osnovannykh na logarifmicheskom preobrazovanii amplitudy vo vremya, s ispol'zovaniem rasshiritelej impul'sov RC; ehto delaetsya v svyazi s ikh primeneniem dlya vyyasneniya voprosa o tom, imeet li opredelennuyu velichinu proizvedenie amplitud dvukh sovpadayushchikh impul'sov. Privodyatsya nekotorye vozmozhnye blok-skhemy. (author)

Time-amplitude converter; Convertisseur temps-amplitude

Energy Technology Data Exchange (ETDEWEB)

Banner, M [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1961-07-01

It is normal in high energy physics to measure the time of flight of a particle in order to determine its mass. This can be done by the method which consists in transforming the time measurement into an analysis of amplitude, which is easier; a time-amplitude converter has therefore been built for this purpose. The apparatus here described uses a double grid control tube 6 BN 6 whose resolution time, as measured with a pulse generator, is 5 x 10{sup -11} s. The analysis of the response of a particle counter, made up of a scintillator and a photomultiplier, indicates that a time of resolution of 5 x 10{sup -10} s. can be obtained. A time of this order of magnitude is obtained experimentally with the converter. This converter has been used in the study of the time of flight of particles in a secondary beam of the accelerator Saturne. It has thus been possible to measure the energy spectrum of {pi}-mesons, of protons, and of deutons emitted from a polyethylene target bombarded by 1,4 and 2 GeV protons. (author) [French] Pour determiner la masse d'une particule, il est courant, en physique des hautes energies, de mesurer le temps de vol de cette particule. Cela peut etre fait par la methode qui consiste a transformer la mesure d'un temps en une analyse d'amplitude, plus aisee; aussi a-t-on, a cet effet, cree un convertisseur temps-amplitude. L'appareillage decrit dans cet article utilise un tube a double grille de commande 6 BN 6 dont le temps de resolution mesure avec un generateur d'impulsion est de 5.10{sup -11} s. L'analyse de la reponse d'un compteur de particules, constitue par un scintillateur et un photomultiplicateur, indique qu'un temps de resolution de 5.10{sup -10} s peut etre obtenu. Un temps de cet ordre est atteint experimentalement avec le convertisseur. Ce convertisseur a servi a l'etude du temps de vol des particules dans un faisceau secondaire de l'accelerateur Saturne. On a mesure ainsi le spectre d'energie des mesons {pi}, des protons, des deutons

Muscarinic receptor subtype mRNA expression in the human prostate: association with age, pathological diagnosis, prostate size, or potentially interfering medications?

NARCIS (Netherlands)

Witte, Lambertus P. W.; Teitsma, Christine A.; de La Rosette, Jean J. M. C. H.; Michel, Martin C.

2014-01-01

As the prostate abundantly expresses muscarinic receptors and antagonists for such receptors are increasingly used in the treatment of men with voiding function and large prostates, we have explored an association of the mRNA expression of human M1, M2, M3, M4, and M5 receptors in human prostate

Proceedings of the International Symposium on Subtypes of Muscarinic Receptors (5th), Held in Newport Beach, California, October 22-24, 1992.

Science.gov (United States)

1993-02-22

AHMED , Chest 96 1285-1291 (1991). 29. P.J. BARNES, Thorax 44 161-167 (1989). 30. P.W. IND, C.M.S. DIXON, R.W. FULLER and P.J. BARNES, Am Rev Respir...mechanism by which muscarinic agonists, such as pilocarpiný_ lower the intraocular pressure of glaucoma patients. Pharmacological studies with subtype

Regional distribution of muscarinic acetylcholine receptors in the telencephalon of the pigeon (Columba livia f. domestica)

International Nuclear Information System (INIS)

Waechtler, K.

1985-01-01

The distribution of muscarinic acetylcholine receptors was studied autoradiographically in croystat sections of the pigeon telencephalon using 3 H-quinuclidinylbenzylate as a ligand. Highest receptor density was observed in the hyperstriatum ventrale, palaeostriatum augmentatum, septum, and parts of the archistriatum. In sites of known sensory input of neostriatum (field L) and ectostriatum low receptor binding was observed. Acetylcholinesterase distribution is in good agreement with the receptor picture only in the basal telencephalon. In the pallium differences in the pattern of these two components can be seen. (author)

Frequency-dependent changes in amplitude of low-frequency oscillations in depression: A resting-state fMRI study.

Science.gov (United States)

Wang, Li; Kong, Qingmei; Li, Ke; Su, Yunai; Zeng, Yawei; Zhang, Qinge; Dai, Wenji; Xia, Mingrui; Wang, Gang; Jin, Zhen; Yu, Xin; Si, Tianmei

2016-02-12

We conducted this fMRI study to examine whether the alterations in amplitudes of low-frequency oscillation (LFO) of major depressive disorder (MDD) patients were frequency dependent. The LFO amplitudes (as indexed by amplitude of low-frequency fluctuation [ALFF] and fractional ALFF [fALFF]) within 4 narrowly-defined frequency bands (slow-5: 0.01-0.027Hz, slow-4: 0.027-0.073Hz, slow-3: 0.073-0.198Hz, and slow-2: 0.198-0.25Hz) were computed using resting-state fMRI data of 35 MDD patients and 32 healthy subjects. Repeated-measures analysis of variance (ANOVA) was performed on ALFF and fALFF both within the low frequency bands of slow-4 and slow-5 and within all of the four bands. We observed significant main effects of group and frequency on ALFF and fALFF in widely distributed brain regions. Importantly, significant group and frequency interaction effects were observed in the ventromedial prefrontal cortex, inferior frontal gyrus, precentral gyrus, in a left-sided fashion, the bilateral posterior cingulate and precuneus, during ANOVA both within slow-4 and slow-5 bands and within all the frequency bands. The results suggest that the alterations of LFO amplitudes in specific brain regions in MDD patients could be more sensitively detected in the slow-5 rather than the slow-4 bands. The findings may provide guidance for the frequency choice of future resting-state fMRI studies of MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PASSIVE-AVOIDANCE TRAINING INDUCES ENHANCED LEVELS OF IMMUNOREACTIVITY FOR MUSCARINIC ACETYLCHOLINE-RECEPTOR AND COEXPRESSED PKC-GAMMA AND MAP-2 IN RAT CORTICAL-NEURONS

NARCIS (Netherlands)

VANDERZEE, EA; DOUMA, BRK; BOHUS, B; LUITEN, PGM

1994-01-01

Changes in neocortical immunoreactivity (ir) for muscarinic acetylcholine receptors (mAChRs), protein kinase C gamma (PKC gamma), microtubule-associated protein 2 (MAP-2), and the calcium-binding protein parvalbumin (PARV) induced by the performance of a one-trial passive shock avoidance (PSA) task

A novel muscarinic receptor ligand which penetrates the blood brain barrier and displays in vivo selectivity for the m2 subtype

International Nuclear Information System (INIS)

Gitler, M.S.; Cohen, V.I.; De La Cruz, R.; Boulay, S.F.; Jin, B.; Zeeberg, B.R.; Reba, R.C.

1993-01-01

Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not m1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of m2 receptors in AD is limited by the fact that there is currently no available m2-selective radioligand which can penetrate the blood-brain barrier. In our efforts to prepare such a radioligand, the authors have used competition studies against currently existing muscarinic receptor radioligands to infer the in vitro and in vivo properties of a novel muscarinic receptor ligand, 5-[[4-[4-(diisobutylamino)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-11-one (DIBD). In vitro competition studies against [ 3 H](R)-3-quinuclidinylbenzilate ([ 3 H]QNB) and [ 3 H]N-methylscopolamine ([ 3 H]NMS), using membranes derived from transfected cells expressing only m1, m2, m3, or m4 receptor subtypes, indicate that DIBD is selective for m2/m4 over m1/m3. In vivo competition studies against (R,R)-[ 125 I]IQNB indicate that DIBD crosses the blood brain barrier (BBB). The relationship of the regional percentage decrease in (R,R)-[ 125 I]IQNB versus the percentage of each of the receptor subtypes indicates that DIBD competes more effectively in those brain regions which are known to be enriched in the m2, relative to the m1, m3, and m4, receptor subtype; however, analysis of the data using a mathematical model shows that caution is required when interpreting the in vivo results. The authors conclude that a suitably radiolabeled derivative of DIBD may be of potential use in emission tomographic study of changes in m2 receptors in the central nervous system

Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer.

Science.gov (United States)

Mannan Baig, Abdul; Khan, Naveed A; Effendi, Vardah; Rana, Zohaib; Ahmad, H R; Abbas, Farhat

2017-01-01

Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.

Altered energy intake and the amplitude of the body temperature rhythm are associated with changes in phase, but not amplitude, of clock gene expression in the rat suprachiasmatic nucleus in vivo.

Science.gov (United States)

Goh, Grace H; Mark, Peter J; Maloney, Shane K

2016-01-01

Circadian rhythms in mammals are driven by a central clock in the suprachiasmatic nucleus (SCN). In vitro, temperature cycles within the physiological range can act as potent entraining cues for biological clocks. We altered the body temperature (Tc) rhythm in rats by manipulating energy intake (EI) to determine whether EI-induced changes in Tc oscillations are associated with changes in SCN clock gene rhythms in vivo. Male Wistar rats (n = 16 per diet) were maintained on either an ad libitum diet (CON), a high energy cafeteria diet (CAF), or a calorie restricted diet (CR), and Tc was recorded every 30 min for 6-7 weeks. SCN tissue was harvested from rats at zeitgeber time (ZT) 0, ZT6, ZT12, or ZT18. Expression of the clock genes Bmal1, Per2, Cry1, and Rev-erbα, the heat shock transcription factor Hsf1, and the heat shock protein Hsp90aa1, were determined using qPCR. The circadian profile of gene expression for each gene was characterized using cosinor analysis. Compared to the CON rats, the amplitude of Tc was decreased in CAF rats by 0.1 °C (p  0.25). Compared to CON, phase advances of the Tc, Bmal1, and Per2 rhythms were observed with CR feeding (p < 0.05), but CAF feeding elicited no significant changes in phase. The present results indicate that in vivo, the SCN is largely resistant to entrainment by EI-induced changes in the Tc rhythm, although some phase entrainment may occur.

Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors

Czech Academy of Sciences Publication Activity Database

Krejčí, Alena; Tuček, Stanislav

2001-01-01

Roč. 60, č. 4 (2001), s. 761-767 ISSN 0026-895X R&D Projects: GA ČR GA309/99/0214 Institutional research plan: CEZ:AV0Z5011922 Keywords : muscarinic receptors * allosteric modulators Subject RIV: FH - Neurology Impact factor: 5.297, year: 2001

Hidden beauty in multiloop amplitudes

International Nuclear Information System (INIS)

Cachazo, Freddy; Spradlin, Marcus; Volovich, Anastasia

2006-01-01

Planar L-loop maximally helicity violating amplitudes in N = 4 supersymmetric Yang-Mills theory are believed to possess the remarkable property of satisfying iteration relations in L. We propose a simple new method for studying iteration relations for four-particle amplitudes which involves the use of certain linear differential operators and eliminates the need to fully evaluate any loop integrals. We carry out this procedure in explicit detail for the two-loop amplitude and prove that this method can be applied to any multiloop integral, allowing a conjectured iteration relation for any given amplitude to be tested up to polynomials in logarithms

Vocal responses of austral forest frogs to amplitude and degradation patterns of advertisement calls.

Science.gov (United States)

Penna, Mario; Moreno-Gómez, Felipe N; Muñoz, Matías I; Cisternas, Javiera

2017-07-01

Degradation phenomena affecting animal acoustic signals may provide cues to assess the distance of emitters. Recognition of degraded signals has been extensively demonstrated in birds, and recently studies have also reported detection of degraded patterns in anurans that call at or above ground level. In the current study we explore the vocal responses of the syntopic burrowing male frogs Eupsophus emiliopugini and E. calcaratus from the South American temperate forest to synthetic conspecific calls differing in amplitude and emulating degraded and non-degraded signal patterns. The results show a strong dependence of vocal responses on signal amplitude, and a general lack of differential responses to signals with different pulse amplitude modulation depths in E. emiliopugini and no effect of relative amplitude of harmonics in E. calcaratus. Such limited discrimination of signal degradation patterns from non-degraded signals is likely related to the burrowing habits of these species. Shelters amplify outgoing and incoming conspecific vocalizations, but do not counteract signal degradation to an extent comparable to calling strategies used by other frogs. The limited detection abilities and resultant response permissiveness to degraded calls in these syntopic burrowing species would be advantageous for animals communicating in circumstances in which signal alteration prevails. Copyright © 2017 Elsevier B.V. All rights reserved.

Muscarinic M1 acetylcholine receptors regulate the non-quantal release of acetylcholine in the rat neuromuscular junction via NO-dependent mechanism

Czech Academy of Sciences Publication Activity Database

Malomouzh, A. I.; Mukhtarov, M. R.; Nikolsky, E. E.; Vyskočil, František

2007-01-01

Roč. 102, č. 6 (2007), s. 2110-2117 ISSN 0022-3042 R&D Projects: GA AV ČR(CZ) IAA5011411; GA MŠk(CZ) LC554 Grant - others:-(RU) 112.0/001/481 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic receptors * NO synthese Subject RIV: ED - Physiology Impact factor: 4.451, year: 2007

Off-shell CHY amplitudes

Energy Technology Data Exchange (ETDEWEB)

Lam, C.S., E-mail: Lam@physics.mcgill.ca [Department of Physics, McGill University, Montreal, Q.C., H3A 2T8 (Canada); Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, V6T 1Z1 (Canada); Yao, York-Peng, E-mail: yyao@umich.edu [Department of Physics, The University of Michigan Ann Arbor, MI 48109 (United States)

2016-06-15

The Cachazo–He–Yuan (CHY) formula for on-shell scattering amplitudes is extended off-shell. The off-shell amplitudes (amputated Green's functions) are Möbius invariant, and have the same momentum poles as the on-shell amplitudes. The working principles which drive the modifications to the scattering equations are mainly Möbius covariance and energy momentum conservation in off-shell kinematics. The same technique is also used to obtain off-shell massive scalars. A simple off-shell extension of the CHY gauge formula which is Möbius invariant is proposed, but its true nature awaits further study.

Geochemical behaviour of uranium in the cycle of alteration; Comportement geochimique de l'uranium dans le cycle d'alteration

Energy Technology Data Exchange (ETDEWEB)

Chervet, J; Coulomb, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Soudan, P [Centre d' Etude de Lalumine, Compagnie Pechiney (France)

1958-07-01

The investigation of the genesis of secondary mineralized accumulations, and the prospecting of deposits from microchemical anomalies in the surface material, is requiring a well-developed knowledge of the geochemical properties of the uranium during the alteration phase. In the present work, the authors tried to track the uranium history during a part of his natural creeping. a) They describe some most typical mineralogical observations of alteration phenomena and material migration, picked up in place on the deposits. b) They give experimental results concerning the solubilities of the uranium minerals and the factors affecting this solubility. c) They study the water circulation in granitic batholites, and the influence of the occurrence of the uranium deposits on their composition. d) They observe the amplitude of phenomena restricting the dispersions: fixations, precipitations, etc., and the behaviour of growth in uraniferous areas. e) Finally, the opposition chemical alteration-radioactive equilibrium results in an important imbalance in altered materials. The authors tried to use the measurement of this imbalance to explain geochemical processes. (author) [French] L'etude des conditions de genese des accumulations minerales secondaires, ainsi que la prospection des gisements a partir d'anomalies microchimiques dans les materiaux de surface, necessite une connaissance approfondie des proprietes geochimiques fondamentales de l'uranium dans la phase d'alteration. Nous essayons, dans ce travail, de suivre l'histoire de l'uranium dans une partie de son cheminement naturel. a) Nous decrivons quelques observations mineralogiques particulierement typiques de phenomenes d'alteration et de migration de matiere, prises 'in situ' dans les gisements. b) Nous donnons les resultats d'experiences de laboratoire sur les solubilites de mineraux d'uranium et sur les facteurs influen nt cette solubilite. c) Nous etudions les circulations d'eaux sur les massifs granitiques et

Experiment K-6-18. Study of muscarinic and gaba (benzodiazepine) receptors in the sensory-motor cortex, hippcampus and spinal code

Science.gov (United States)

Daunton, N.; Damelio, F.; Krasnov, I.

1990-01-01

Frontal lobe samples of rat brains flown aboard Cosmos 1887 were processed for the study of muscarinic (cholinergic) and GABA (benzodiazepine) receptors and for immunocytochemical localization of the neurotransmitter gamma-aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP). Although radioactive labeling of both muscarinic cholinergic and GABA (benzodiazepine) receptors proved to be successful with the techniques employed, distinct receptor localization of individual laminae of the frontal neocortex was not possible since the sampling of the area was different in the various groups of animals. In spite of efforts made for proper orientation and regional identification of laminae, it was found that a densitometric (quantitation of autoradiograms) analysis of the tissue did not contribute to the final interpretation of the effects of weightlessness on these receptors. As to the immunocytochemical studies the use of both markers, GFAP and GABA antiserum, confirmed the suitability of the techniques for use in frozen material. However, similar problems to those encountered in the receptor studies prevented an adequate interpretation of the effects of micro-G exposure on the localization and distribution of GABA and GFAP. This study did, however, confirm the feasibility of investigating neurotransmitters and their receptors in future space flight experiments.

Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction.

Science.gov (United States)

Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria Angel; Cilleros, Victor; Tomàs, Josep Maria

2016-01-01

The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo. In a previous study we analyzed the role of each of the individual receptors. Here we investigate the additive or occlusive effects of their inhibitors and thus the existence of synergistic activity between the receptors. The main results show that the A2A, M1, M4, and A1 receptors (in this order of ability) delayed axonal elimination at P7. M4 produces some occlusion of the M1 pathway and some addition to the A1 pathway, which suggests that they cooperate. M2 receptors may modulate (by allowing a permissive action) the other receptors, mainly M4 and A1. The continued action of these receptors (now including M2 but not M4) finally promotes axonal loss at P9. All 4 receptors (M2, M1, A1, and A2A, in this order of ability) are necessary. The M4 receptor (which in itself does not affect axon loss) seems to modulate the other receptors. We found a synergistic action between the M1, A1, and A2A receptors, which show an additive effect, whereas the potent M2 effect is largely independent of the other receptors (though can be modulated by M4). At P9, there is a full mutual dependence between the A1 and A2A receptors in regulating axon loss. In summary, postnatal axonal elimination is a regulated multireceptor mechanism that involves the cooperation of several muscarinic and adenosine receptor subtypes. �

Exposure to Gulf War Illness chemicals induces functional muscarinic receptor maladaptations in muscle nociceptors.

Science.gov (United States)

Cooper, B Y; Johnson, R D; Nutter, T J

2016-05-01

Chronic pain is a component of the multisymptom disease known as Gulf War Illness (GWI). There is evidence that pain symptoms could have been a consequence of prolonged and/or excessive exposure to anticholinesterases and other GW chemicals. We previously reported that rats exposed, for 8 weeks, to a mixture of anticholinesterases (pyridostigmine bromide, chlorpyrifos) and a Nav (voltage activated Na(+) channel) deactivation-inhibiting pyrethroid, permethrin, exhibited a behavior pattern that was consistent with a delayed myalgia. This myalgia-like behavior was accompanied by persistent changes to Kv (voltage activated K(+)) channel physiology in muscle nociceptors (Kv7, KDR). In the present study, we examined how exposure to the above agents altered the reactivity of Kv channels to a muscarinic receptor (mAChR) agonist (oxotremorine-M). Comparisons between muscle nociceptors harvested from vehicle and GW chemical-exposed rats revealed that mAChR suppression of Kv7 activity was enhanced in exposed rats. Yet in these same muscle nociceptors, a Stromatoxin-insensitive component of the KDR (voltage activated delayed rectifier K(+) channel) exhibited decreased sensitivity to activation of mAChR. We have previously shown that a unique mAChR-induced depolarization and burst discharge (MDBD) was exaggerated in muscle nociceptors of rats exposed to GW chemicals. We now provide evidence that both muscle and vascular nociceptors of naïve rats exhibit MDBD. Examination of the molecular basis of the MDBD in naïve animals revealed that while the mAChR depolarization was independent of Kv7, the action potential burst was modulated by Kv7 status. mAChR depolarizations were shown to be dependent, in part, on TRPA1. We argue that dysfunction of the MDBD could be a functional convergence point for maladapted ion channels and receptors consequent to exposure to GW chemicals. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of amplitude and latency of motor evoked potential by direction of transcranial magnetic stimulation

Science.gov (United States)

Sato, Aya; Torii, Tetsuya; Iwahashi, Masakuni; Itoh, Yuji; Iramina, Keiji

2014-05-01

The present study analyzed the effects of monophasic magnetic stimulation to the motor cortex. The effects of magnetic stimulation were evaluated by analyzing the motor evoked potentials (MEPs). The amplitude and latency of MEPs on the abductor pollicis brevis muscle were used to evaluate the effects of repetitive magnetic stimulation. A figure eight-shaped flat coil was used to stimulate the region over the primary motor cortex. The intensity of magnetic stimulation was 120% of the resting motor threshold, and the frequency of magnetic stimulation was 0.1 Hz. In addition, the direction of the current in the brain was posterior-anterior (PA) or anterior-posterior (AP). The latency of MEP was compared with PA and AP on initial magnetic stimulation. The results demonstrated that a stimulus in the AP direction increased the latency of the MEP by approximately 2.5 ms. MEP amplitude was also compared with PA and AP during 60 magnetic stimulations. The results showed that a stimulus in the PA direction gradually increased the amplitude of the MEP. However, a stimulus in the AP direction did not modulate the MEP amplitude. The average MEP amplitude induced from every 10 magnetic pulses was normalized by the average amplitude of the first 10 stimuli. These results demonstrated that the normalized MEP amplitude increased up to approximately 150%. In terms of pyramidal neuron indirect waves (I waves), magnetic stimulation inducing current flowing backward to the anterior preferentially elicited an I1 wave, and current flowing forward to the posterior elicited an I3 wave. It has been reported that the latency of the I3 wave is approximately 2.5 ms longer than the I1 wave elicitation, so the resulting difference in latency may be caused by this phenomenon. It has also been reported that there is no alteration of MEP amplitude at a frequency of 0.1 Hz. However, this study suggested that the modulation of MEP amplitude depends on stimulation strength and stimulation direction.

New relations for Einstein–Yang–Mills amplitudes

International Nuclear Information System (INIS)

Stieberger, Stephan; Taylor, Tomasz R.

2016-01-01

We obtain new relations between Einstein–Yang–Mills (EYM) amplitudes involving N gauge bosons plus a single graviton and pure Yang–Mills amplitudes involving N gauge bosons plus one additional vector boson inserted in a way typical for a gauge boson of a “spectator” group commuting with the group associated to original N gauge bosons. We show that such EYM amplitudes satisfy U(1) decoupling relations similar to Kleiss–Kuijf relations for Yang–Mills amplitudes. We consider a D-brane embedding of EYM amplitudes in the framework of disk amplitudes involving open and closed strings. A new set of monodromy relations is derived for mixed open–closed amplitudes with one closed string inserted on the disk world-sheet and a number of open strings at the boundary. These relations allow expressing the latter in terms of pure open string amplitudes and, in the field-theory limit, they yield the U(1) decoupling relations for EYM amplitudes.

Distinct muscarinic acetylcholine receptor subtypes mediate pre- and postsynaptic effects in rat neocortex

Directory of Open Access Journals (Sweden)

Gigout Sylvain

2012-04-01

Full Text Available Abstract Background Cholinergic transmission has been implicated in learning, memory and cognition. However, the cellular effects induced by muscarinic acetylcholine receptors (mAChRs activation are poorly understood in the neocortex. We investigated the effects of the cholinergic agonist carbachol (CCh and various agonists and antagonists on neuronal activity in rat neocortical slices using intracellular (sharp microelectrode and field potential recordings. Results CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronal firing was antagonized by pirenzepine (M1/M4 mAChRs antagonist but not by AF-DX 116 (M2/M4 mAChRs antagonist. Pirenzepine reversed the depressant effect of CCh on excitatory postsynaptic potential (EPSP but had marginal effects when applied before CCh. AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CCh also decreased the paired-pulse inhibition of field potentials and the inhibitory conductances mediated by GABAA and GABAB receptors. The depression of paired-pulse inhibition was antagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. The inhibitory conductances were unaltered by xanomeline (M1/M4 mAChRs agonist, yet the CCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-current blocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effect on the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current is involved in the increase of neuronal excitability but neither in the depression of EPSP nor paired-pulse inhibition. Conclusions These data indicate that the three effects are mediated by different mAChRs, the increase in firing being mediated by M1 mAChR, decrease of inhibition by M2 mAChR and depression of excitatory transmission by M4 mAChR. The depression of EPSP and increase of neuronal firing might enhance the signal-to-noise ratio, whereas the

Motivic amplitudes and cluster coordinates

International Nuclear Information System (INIS)

Golden, J.K.; Goncharov, A.B.; Spradlin, M.; Vergu, C.; Volovich, A.

2014-01-01

In this paper we study motivic amplitudes — objects which contain all of the essential mathematical content of scattering amplitudes in planar SYM theory in a completely canonical way, free from the ambiguities inherent in any attempt to choose particular functional representatives. We find that the cluster structure on the kinematic configuration space Conf n (ℙ 3 ) underlies the structure of motivic amplitudes. Specifically, we compute explicitly the coproduct of the two-loop seven-particle MHV motivic amplitude A 7,2 M and find that like the previously known six-particle amplitude, it depends only on certain preferred coordinates known in the mathematics literature as cluster X-coordinates on Conf n (ℙ 3 ). We also find intriguing relations between motivic amplitudes and the geometry of generalized associahedrons, to which cluster coordinates have a natural combinatoric connection. For example, the obstruction to A 7,2 M being expressible in terms of classical polylogarithms is most naturally represented by certain quadrilateral faces of the appropriate associahedron. We also find and prove the first known functional equation for the trilogarithm in which all 40 arguments are cluster X-coordinates of a single algebra. In this respect it is similar to Abel’s 5-term dilogarithm identity

Membrane cholesterol content influences binding properties of muscarinic M2 receptors and differentially impacts activation of second messenger pathways

Czech Academy of Sciences Publication Activity Database

Michal, Pavel; Rudajev, Vladimír; El-Fakahany, E. E.; Doležal, Vladimír

2009-01-01

Roč. 606, 1-3 (2009), s. 50-60 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA305/05/0452; GA AV ČR(CZ) IAA500110703; GA MŠk(CZ) LC554 Grant - others:National Institutes of Health(US) NS25743; EC(XE) LipiDiDiet Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic * cholesterol * receptors Subject RIV: ED - Physiology Impact factor: 2.585, year: 2009

Synthesis of dibenzodioxazocines and their effects on cholinesterases and muscarinic cholinergic receptors.

Science.gov (United States)

Gaál, J; Batke, J; Borsodi, A; Rózsa, L; Somogyi, G

1989-01-01

A new family of tricyclic compounds, the dibenzodioxazocines were synthesized. These compounds were the following: 2-chloro-12-(2-piperidino-ethyl)-dibenzo d,g 1,3,6 dioxazocine hydrochloride: EGYT-2347, 2-chloro-12-(3-dimethylamino-2-methyl-propyl)-dibenzo [d,g] [1,3,6]-dibenzodioxazocine hydrochloride: EGYT-2509, 2-chloro-12-(3-dimethylamino-propyl)-dibenzo [d,g] [1,3,6] dioxazocine-maleate: EGYT-2474 and 2-chloro-12-2-(4-methyl-piperazino)-ethyl-dibenzo [d,g] [1,3,6]-dioxazocine-dihydrochloride: EGYT-2541. These compounds are inhibitors of both butyryl- and acetylcholinesterase to and they exhibited relatively good anticholinergic properties in receptor binding experiments. The most selective inhibitor of butyrylcholinesterase is the compound EGYT-2347 (Ki = 1.5 x 10(-7) M) which strongly binds to rat brain muscarinic cholinergic receptor (KD = 4.1 x 10(-8) M).

Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory.

Science.gov (United States)

Ferreira, G; Gutiérrez, R; De La Cruz, V; Bermúdez-Rattoni, F

2002-09-01

In conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste-illness association.

Two Photon Distribution Amplitudes

International Nuclear Information System (INIS)

El Beiyad, M.; Pire, B.; Szymanowski, L.; Wallon, S.

2008-01-01

The factorization of the amplitude of the process γ*γ→γγ in the low energy and high photon virtuality region is demonstrated at the Born order and in the leading logarithmic approximation. The leading order two photon (generalized) distribution amplitudes exhibit a characteristic ln Q 2 behaviour and obey new inhomogeneous evolution equations

Wash-Resistantly Bound Xanomeline Inhibits Acetylcholine Release by Persistent Activation of Presynaptic M2 and M4 Muscarinic Receptors in Rat Brain

Czech Academy of Sciences Publication Activity Database

Machová, Eva; Jakubík, Jan; El-Fakahany, E. E.; Doležal, Vladimír

2007-01-01

Roč. 322, č. 1 (2007), s. 316-323 ISSN 0022-3565 R&D Projects: GA ČR(CZ) GA305/05/0452; GA MŠk(CZ) LC554 Grant - others:-(US) NS25743 Institutional research plan: CEZ:AV0Z50110509 Keywords : acetylcholine * xanomeline * muscarinic receptor Subject RIV: ED - Physiology Impact factor: 4.003, year: 2007

The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

DEFF Research Database (Denmark)

Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

2003-01-01

(EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates......Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects...

Relative amplitude preservation processing utilizing surface consistent amplitude correction. Part 3; Surface consistent amplitude correction wo mochiita sotai shinpuku hozon shori. 3

Energy Technology Data Exchange (ETDEWEB)

Saeki, T [Japan National Oil Corporation, Tokyo (Japan). Technology Research Center

1996-10-01

For the seismic reflection method conducted on the ground surface, generator and geophone are set on the surface. The observed waveforms are affected by the ground surface and surface layer. Therefore, it is required for discussing physical properties of the deep underground to remove the influence of surface layer, preliminarily. For the surface consistent amplitude correction, properties of the generator and geophone were removed by assuming that the observed waveforms can be expressed by equations of convolution. This is a correction method to obtain records without affected by the surface conditions. In response to analysis and correction of waveforms, wavelet conversion was examined. Using the amplitude patterns after correction, the significant signal region, noise dominant region, and surface wave dominant region would be separated each other. Since the amplitude values after correction of values in the significant signal region have only small variation, a representative value can be given. This can be used for analyzing the surface consistent amplitude correction. Efficiency of the process can be enhanced by considering the change of frequency. 3 refs., 5 figs.

New relations for gauge-theory amplitudes

International Nuclear Information System (INIS)

Bern, Z.; Carrasco, J. J. M.; Johansson, H.

2008-01-01

We present an identity satisfied by the kinematic factors of diagrams describing the tree amplitudes of massless gauge theories. This identity is a kinematic analog of the Jacobi identity for color factors. Using this we find new relations between color-ordered partial amplitudes. We discuss applications to multiloop calculations via the unitarity method. In particular, we illustrate the relations between different contributions to a two-loop four-point QCD amplitude. We also use this identity to reorganize gravity tree amplitudes diagram by diagram, offering new insight into the structure of the Kawai-Lewellen-Tye (KLT) relations between gauge and gravity tree amplitudes. This insight leads to similar but novel relations. We expect this to be helpful in higher-loop studies of the ultraviolet properties of gravity theories.

Multiscalar production amplitudes beyond threshold

CERN Document Server

Argyres, E N; Kleiss, R H

1993-01-01

We present exact tree-order amplitudes for $H^* \\to n~H$, for final states containing one or two particles with non-zero three-momentum, for various interaction potentials. We show that there are potentials leading to tree amplitudes that satisfy unitarity, not only at threshold but also in the above kinematical configurations and probably beyond. As a by-product, we also calculate $2\\to n$ tree amplitudes at threshold and show that for the unbroken $\\phi^4$ theory they vanish for $n>4~$, for the Standard Model Higgs they vanish for $n\\ge 3~$ and for a model potential, respecting tree-order unitarity, for $n$ even and $n>4~$. Finally, we calculate the imaginary part of the one-loop $1\\to n$ amplitude in both symmetric and spontaneously broken $\\phi^4$ theory.

Changes in Membrane Cholesterol Differentially Influence Preferential and Non-preferential Signaling of the M1 and M3 Muscarinic Acetylcholine Receptors

Czech Academy of Sciences Publication Activity Database

Michal, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

2015-01-01

Roč. 40, č. 10 (2015), s. 2068-2070 ISSN 0364-3190 R&D Projects: GA ČR(CZ) GA14-05696S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) 7E10060 Institutional support: RVO:67985823 Keywords : muscarinic receptors * agonist binding * cholesterol * G-proteins * signal transduction * cAMP synthesis Subject RIV: FH - Neurology Impact factor: 2.472, year: 2015

The Effects of Nicotinic and Muscarinic Receptor Activation on Patch-Clamped Cells in the Optic Tectum of Rana Pipiens

OpenAIRE

Yu, C.-J.; Debski, E. A.

2003-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 μM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in sponta...

A numerical study on the impact of nonlinear interactions on the amplitude of the migrating semidiurnal tide

Directory of Open Access Journals (Sweden)

C. M. Huang

2006-12-01

Full Text Available To quantitatively study the effects of nonlinear interactions on tide structure, a nonlinear numerical tidal model is developed, and the reliability and convergence of the adopted algorithm and coding are checked by numerical experiments. Under the same conditions as those employed by the GSWM-00 (Global Scale Wave Model 2000, our model provides the nonlinear quasi-steady solution of the migrating semidiurnal tide, which differs from the GSWM-00 result (the linear steady solution in the MLT region, especially above 100 km. Additionally, their amplitude difference displays a remarkable month-to-month variation, and its significant magnitudes occur during the month with strong semidiurnal tide. A quantitative analysis suggests that the main cause for the amplitude difference is that the initial migrating 12-h tide will interact with the mean flow as well as the nonlinearity-excited 6-h tide, and subsequently yield a new 12-h tidal part. Furthermore, our simulations also show that the mean flow/tidal interaction will significantly alter the background wind and temperature fields. The large magnitudes of the tidal amplitude difference and the background alteration indicate that the nonlinear processes involved in tidal propagations should be comprehensively considered in the description of global atmospheric dynamics in the MLT region. The comparisons among our simulations, the GSWMs and some observations of tides suggest that the nonlinearity-induced tidal structure variation could be a possible mechanism to account for some discrepancies between the GSWMs and the observations.

Muscarinic receptors in amygdala control trace fear conditioning.

Directory of Open Access Journals (Sweden)

Amber N Baysinger

Full Text Available Intelligent behavior requires transient memory, which entails the ability to retain information over short time periods. A newly-emerging hypothesis posits that endogenous persistent firing (EPF is the neurophysiological foundation for aspects or types of transient memory. EPF is enabled by the activation of muscarinic acetylcholine receptors (mAChRs and is triggered by suprathreshold stimulation. EPF occurs in several brain regions, including the lateral amygdala (LA. The present study examined the role of amygdalar mAChRs in trace fear conditioning, a paradigm that requires transient memory. If mAChR-dependent EPF selectively supports transient memory, then blocking amygdalar mAChRs should impair trace conditioning, while sparing delay and context conditioning, which presumably do not rely upon transient memory. To test the EPF hypothesis, LA was bilaterally infused, prior to trace or delay conditioning, with either a mAChR antagonist (scopolamine or saline. Computerized video analysis quantified the amount of freezing elicited by the cue and by the training context. Scopolamine infusion profoundly reduced freezing in the trace conditioning group but had no significant effect on delay or context conditioning. This pattern of results was uniquely anticipated by the EPF hypothesis. The present findings are discussed in terms of a systems-level theory of how EPF in LA and several other brain regions might help support trace fear conditioning.

Muscarinic receptors in amygdala control trace fear conditioning.

Science.gov (United States)

Baysinger, Amber N; Kent, Brianne A; Brown, Thomas H

2012-01-01

Intelligent behavior requires transient memory, which entails the ability to retain information over short time periods. A newly-emerging hypothesis posits that endogenous persistent firing (EPF) is the neurophysiological foundation for aspects or types of transient memory. EPF is enabled by the activation of muscarinic acetylcholine receptors (mAChRs) and is triggered by suprathreshold stimulation. EPF occurs in several brain regions, including the lateral amygdala (LA). The present study examined the role of amygdalar mAChRs in trace fear conditioning, a paradigm that requires transient memory. If mAChR-dependent EPF selectively supports transient memory, then blocking amygdalar mAChRs should impair trace conditioning, while sparing delay and context conditioning, which presumably do not rely upon transient memory. To test the EPF hypothesis, LA was bilaterally infused, prior to trace or delay conditioning, with either a mAChR antagonist (scopolamine) or saline. Computerized video analysis quantified the amount of freezing elicited by the cue and by the training context. Scopolamine infusion profoundly reduced freezing in the trace conditioning group but had no significant effect on delay or context conditioning. This pattern of results was uniquely anticipated by the EPF hypothesis. The present findings are discussed in terms of a systems-level theory of how EPF in LA and several other brain regions might help support trace fear conditioning.

Amplitude structure of off-shell processes

International Nuclear Information System (INIS)

Fearing, H.W.; Goldstein, G.R.; Moravcsik, M.J.

1984-01-01

The structure of M matrices, or scattering amplitudes, and of potentials for off-shell processes is discussed with the objective of determining how one can obtain information on off-shell amplitudes of a process in terms of the physical observables of a larger process in which the first process is embedded. The procedure found is inevitably model dependent, but within a particular model for embedding, a determination of the physically measurable amplitudes of the larger process is able to yield a determination of the off-shell amplitudes of the embedded process

Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; El-Fakahany, E. E.; Doležal, Vladimír

2006-01-01

Roč. 70, č. 2 (2006), s. 656-666 ISSN 0026-895X R&D Projects: GA ČR(CZ) GA305/05/0452; GA MŠk(CZ) LC554 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z5011922 Keywords : xanomeline * muscarinic receptors * G-protein activation Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 4.469, year: 2006

Functional Characterization of CCHamide and Muscarinic Acetylcholine Receptor Signalling in Drosophila melanogaster

DEFF Research Database (Denmark)

Ren, Guilin Robin

G-protein coupled receptors (GPCRs) constitute a large and ancient superfamily of membraneproteins responsible for the transduction of extracellular signals to the inside of the cells. In thisPh.D. thesis, Drosophila melanogaster (Dm) was used as a model organism to investigate a numberof topics...... is a newly discovered insect peptide hormone. The function of this novel peptide hasnot been well characterised. In this Ph.D. thesis, I identified CCHamide-2 peptides in endocrinecells of the gut and neurones of the brain of larvae and endocrine cells of the gut of adultDrosophila. Behavioural assays...... little is known about muscarinic acetylcholine receptorsignalling in insects. In this study, I found that two types of mAChRs occur in D. melanogaster, onecoupling to Gq (A-type) and the other to Gi (B-type). Both A- and B-type Dm-mAChRs can beactivated by acetylcholine (ACh), but the classical...

Non-supersymmetric loop amplitudes and MHV vertices

International Nuclear Information System (INIS)

Bedford, James; Brandhuber, Andreas; Spence, Bill; Travaglini, Gabriele

2005-01-01

We show how the MHV diagram description of Yang-Mills theories can be used to study non-supersymmetric loop amplitudes. In particular, we derive a compact expression for the cut-constructible part of the general one-loop MHV multi-gluon scattering amplitude in pure Yang-Mills theory. We show that in special cases this expression reduces to known amplitudes-the amplitude with adjacent negative-helicity gluons, and the five gluon non-adjacent amplitude. Finally, we briefly discuss the twistor space interpretation of our result

Coupling of g proteins to reconstituted monomers and tetramers of the M2 muscarinic receptor.

Science.gov (United States)

Redka, Dar'ya S; Morizumi, Takefumi; Elmslie, Gwendolynne; Paranthaman, Pranavan; Shivnaraine, Rabindra V; Ellis, John; Ernst, Oliver P; Wells, James W

2014-08-29

G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5'-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[(3)H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the "ternary complex model"). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Scattering amplitudes in gauge theories

CERN Document Server

Henn, Johannes M

2014-01-01

At the fundamental level, the interactions of elementary particles are described by quantum gauge field theory. The quantitative implications of these interactions are captured by scattering amplitudes, traditionally computed using Feynman diagrams. In the past decade tremendous progress has been made in our understanding of and computational abilities with regard to scattering amplitudes in gauge theories, going beyond the traditional textbook approach. These advances build upon on-shell methods that focus on the analytic structure of the amplitudes, as well as on their recently discovered hidden symmetries. In fact, when expressed in suitable variables the amplitudes are much simpler than anticipated and hidden patterns emerge.   These modern methods are of increasing importance in phenomenological applications arising from the need for high-precision predictions for the experiments carried out at the Large Hadron Collider, as well as in foundational mathematical physics studies on the S-matrix in quantum ...

Muscarinic acetylcholine receptors: location of the ligand binding site

International Nuclear Information System (INIS)

Hulme, E.; Wheatley, M.; Curtis, C.; Birdsall, N.

1987-01-01

The key to understanding the pharmacological specificity of muscarinic acetylcholine receptors (mAChR's) is the location within the receptor sequence of the amino acid residues responsible for ligand binding. To approach this problem, they have purified mAChR's from rat brain to homogeneity by sequential ion-exchange chromatography, affinity chromatography and molecular weight fractionation. Following labelling of the binding site with an alkylating affinity label, 3 H-propylbenzilycholine mustard aziridinium ion ( 3 H-PrBCM), the mAChR was digested with a lysine-specific endoproteinase, and a ladder of peptides of increasing molecular weight, each containing the glycosylated N-terminus, isolated by chromatography on wheat-germ agglutinin sepharose. The pattern of labelling showed that a residue in the peptides containing transmembrane helices 2 and/or 3 of the mAChR was alkylated. The linkage was cleaved by 1 M hydroxylamine, showing that 3 H-PrBCM was attached to an acidic residue, whose properties strongly suggested it to be embedded in a hydrophobic intramembrane region of the mAChR. Examination of the cloned sequence of the mAChR reveals several candidate residues, the most likely of which is homologous to an aspartic acid residue thought to protonate the retinal Schiff's base in the congeneric protein rhodopsin

Analytical properties of multiple production amplitudes

Energy Technology Data Exchange (ETDEWEB)

Medvedev, B V; Pavlov, V P; Polivanov, M K; Sukhanov, A D [Gosudarstvennyj Komitet po Ispol' zovaniyu Atomnoj Ehnergii SSSR, Moscow. Inst. Teoreticheskoj i Ehksperimental' noj Fiziki; AN SSSR, Moscow. Matematicheskij Inst.)

1984-05-01

Local analytical properties of amplitudes 2..-->..3 and 2..-->..4 are studied. The amplitudes are shown to be analytical functions of total and partial energies at fixed momentum transfers in the neighbourhood of any physical point on the energy shell 14 (for the 2..-->..3 case) and 242 (for the 2..-->..4 case) boundary values are expressed through the amplitudes of real processes.

Mutations in the third extracellular loop of M3 muscarinic receptor induce positive cooperativity between N-Methylscopolamine and Wieland-Gumlich aldehyde

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Doležal, Vladimír

2005-01-01

Roč. 272, č. S1 (2005), s. 221-221 ISSN 1474-3833. [FEBS Congress /30./ and IUBMB Conference /9./. 02.07.2005-07.07.2005, Budapest] R&D Projects: GA AV ČR(CZ) IAA5011306; GA ČR(CZ) GP305/02/D090 Institutional research plan: CEZ:AV0Z5011922 Keywords : muscarinic receptors * allosteric interaction * strychnine -like modulators * mutations * extracellular loop Subject RIV: ED - Physiology

Determination of backward pion nucleon scattering amplitudes

International Nuclear Information System (INIS)

Pietarinen, E.

1978-04-01

Backward C(sup(+-))πN amplitudes are determined from πN→Nπ and NantiN→2π differential cross sections in such a way that they are consistent with the analyticity properties and information of the unphysical ππ→NantiN amplitudes. Combining the result with forward C(sup(+-)) amplitudes positive and negative parity resonances are extracted. An error analysis of the amplitudes is performed. (author)

Scattering amplitudes in open superstring theory

Energy Technology Data Exchange (ETDEWEB)

Schlotterer, Oliver

2011-07-15

The present thesis deals with the theme field of the scattering amplitudes in theories of open superstrings. Especially two different formalisms for the handling of superstrings are introduced and applied for the calaculation of tree-level amplitudes - the Ramond- Neveu-Schwarz (RNS) and the Pure-Spinor (PS) formalism. The RNS approach is proved as flexible in order to describe compactification of the initially ten flat space-time dimensions to four dimensions. We solve the technical problems, which result from the interacting basing world-sheet theory with conformal symmetry. This is used to calculate phenomenologically relevant scattering amplitudes of gluons and quarks as well as production rates of massive harmonic vibrations, which were already identified as virtual exchange particles on the massless level. In the case of a low string mass scale in the range of some Tev the string-specific signatures in parton collisions can be observed in the near future in the LHC experiment at CERN and indicated as first experimental proof of the string theory. THose string effects occur universally for a wide class of string ground states respectively internal geometries and represent an elegant way to avoid the so-called landscape problem of the string theory. A further theme complex in this thesis is based on the PS formalism, which allows a manifestly supersymmetric treatment of scattering amplitudes in ten space-time dimension with sixteen supercharges. We introduce a family of superfields, which occur in massless amplitudes of the open string and can be naturally identified with diagrams of three-valued knots. Thereby we reach not only a compact superspace representation of the n-point field-theory amplitude but can also write the complete superstring n-point amplitude as minimal linear combination of partial amplitudes of the field theory as well as hypergeometric functions. The latter carry the string effects and are analyzed from different perspectives, above all

Scattering amplitudes in open superstring theory

International Nuclear Information System (INIS)

Schlotterer, Oliver

2011-01-01

The present thesis deals with the theme field of the scattering amplitudes in theories of open superstrings. Especially two different formalisms for the handling of superstrings are introduced and applied for the calaculation of tree-level amplitudes - the Ramond- Neveu-Schwarz (RNS) and the Pure-Spinor (PS) formalism. The RNS approach is proved as flexible in order to describe compactification of the initially ten flat space-time dimensions to four dimensions. We solve the technical problems, which result from the interacting basing world-sheet theory with conformal symmetry. This is used to calculate phenomenologically relevant scattering amplitudes of gluons and quarks as well as production rates of massive harmonic vibrations, which were already identified as virtual exchange particles on the massless level. In the case of a low string mass scale in the range of some Tev the string-specific signatures in parton collisions can be observed in the near future in the LHC experiment at CERN and indicated as first experimental proof of the string theory. THose string effects occur universally for a wide class of string ground states respectively internal geometries and represent an elegant way to avoid the so-called landscape problem of the string theory. A further theme complex in this thesis is based on the PS formalism, which allows a manifestly supersymmetric treatment of scattering amplitudes in ten space-time dimension with sixteen supercharges. We introduce a family of superfields, which occur in massless amplitudes of the open string and can be naturally identified with diagrams of three-valued knots. Thereby we reach not only a compact superspace representation of the n-point field-theory amplitude but can also write the complete superstring n-point amplitude as minimal linear combination of partial amplitudes of the field theory as well as hypergeometric functions. The latter carry the string effects and are analyzed from different perspectives, above all

Simultaneous determination of mushroom toxins α-amanitin, β-amanitin and muscarine in human urine by solid-phase extraction and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry.

Science.gov (United States)

Tomková, Jana; Ondra, Peter; Válka, Ivo

2015-06-01

This paper presents a method for the simultaneous determination of α-amanitin, β-amanitin and muscarine in human urine by solid-phase extraction (SPE) and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. The method can be used for a diagnostics of mushroom poisonings. Different SPE cartridges were tested for sample preparation, namely hydrophilic modified reversed-phase (Oasis HLB) and polymeric weak cation phase (Strata X-CW). The latter gave better results and therefore it was chosen for the subsequent method optimization and partial validation. In the course of validation, limits of detection, linearity, intraday and interday precisions and recoveries were evaluated. The obtained LOD values of α-amanitin and β-amanitin were 1ng/mL and of muscarine 0.09ng/mL. The intraday and interday precisions of human urine spiked with α-amanitin (10ng/mL), β-amanitin (10ng/mL) and muscarine (1ng/mL) ranged from 6% to 10% and from 7% to 13%, respectively. The developed method was proved to be a relevant tool for the simultaneous determination of the studied mushroom toxins in human urine after mushroom poisoning. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Color-Kinematics Duality for QCD Amplitudes

CERN Document Server

Johansson, Henrik

2016-01-01

We show that color-kinematics duality is present in tree-level amplitudes of quantum chromodynamics with massive flavored quarks. Starting with the color structure of QCD, we work out a new color decomposition for n-point tree amplitudes in a reduced basis of primitive amplitudes. These primitives, with k quark-antiquark pairs and (n-2k) gluons, are taken in the (n-2)!/k! Melia basis, and are independent under the color-algebra Kleiss-Kuijf relations. This generalizes the color decomposition of Del Duca, Dixon, and Maltoni to an arbitrary number of quarks. The color coefficients in the new decomposition are given by compact expressions valid for arbitrary gauge group and representation. Considering the kinematic structure, we show through explicit calculations that color-kinematics duality holds for amplitudes with general configurations of gluons and massive quarks. The new (massive) amplitude relations that follow from the duality can be mapped to a well-defined subset of the familiar BCJ relations for gluo...

Identification of four areas each enriched in a unique muscarinic receptor subtype

International Nuclear Information System (INIS)

Hoss, W.; Ellerbrock, B.R.; Goldman, P.S.; Collins, D.A.; Messer, W.S. Jr.

1990-01-01

The affinities of muscarinic agonists and antagonists were determined by autoradiography and image analysis in selected areas of the rat brain. IC 50 values and Hill coefficients for the inhibition of the binding of 0.2 nM [ 3 H]-QNB to dentate gyrus, superior colliculus, rhomboid thalamus and substantia nigra were measured in coronal sections. Pirenzepine displayed a high affinity for receptors in the dentate gyrus and AF-DX 116, the superior colliculus. Both pirenzepine and AF-DX 116 had high affinities for the substantia nigra and low affinities for the rhomboid thalamus. Gallamine displayed a 50-fold preference for superior colliculus over dentate gyrus receptors. Amitriptyline was less selective, showing a modest preference for substantia nigra receptors and 4-DAMP was essentially nonselective. Carbachol was the most selective agonist with a 4000-fold preference for superior colliculus over dentate gyrus receptors. Other agonists except RS 86 were also selective for superior colliculus receptors in the order carbachol >> arecoline > bethanechol > McN A343 = oxotremorine = pilocarpine

Analytic continuation of dual Feynman amplitudes

International Nuclear Information System (INIS)

Bleher, P.M.

1981-01-01

A notion of dual Feynman amplitude is introduced and a theorem on the existence of analytic continuation of this amplitude from the convergence domain to the whole complex is proved. The case under consideration corresponds to massless power propagators and the analytic continuation is constructed on the propagators powers. Analytic continuation poles and singular set of external impulses are found explicitly. The proof of the theorem on the existence of analytic continuation is based on the introduction of α-representation for dual Feynman amplitudes. In proving, the so-called ''trees formula'' and ''trees-with-cycles formula'' are established that are dual by formulation to the trees and 2-trees formulae for usual Feynman amplitudes. (Auth.)

Dual effects of muscarinic M2 acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists

Czech Academy of Sciences Publication Activity Database

Michal, Pavel; Lysíková, Michaela; Tuček, Stanislav

2001-01-01

Roč. 132, č. 6 (2001), s. 1217-1228 ISSN 0007-1188 R&D Projects: GA ČR GA309/99/0214; GA AV ČR IAA7011910 Institutional research plan: CEZ:AV0Z5011922 Keywords : cyclic AMP * muscarinic receptors * CHO cells Subject RIV: ED - Physiology Impact factor: 3.502, year: 2001

Amplitude by peak interaction but no evidence of auditory mismatch response deficits to frequency change in preschool age children with FASD.

Science.gov (United States)

Kabella, Danielle M; Flynn, Lucinda; Peters, Amanda; Kodituwakku, Piyadasa; Stephen, Julia M

2018-05-24

Prior studies indicate that the auditory mismatch response is sensitive to early alterations in brain development in multiple developmental disorders. Prenatal alcohol exposure is known to impact early auditory processing. The current study hypothesized alterations in the mismatch response in young children with FASD. Participants in this study were 9 children with a fetal alcohol spectrum disorder and 17 control children (Control) aged 3 to 6 years. Participants underwent MEG and structural MRI scans separately. We compared groups on neurophysiological Mismatch Negativity (MMN) responses to auditory stimuli measured using the auditory oddball paradigm. Frequent (1000 Hz) and rare (1200Hz) tones were presented at 72 dB. There was no significant group difference in MMN response latency or amplitude represented by the peak located ~200 ms after stimulus presentation in the difference timecourse between frequent and infrequent tones. Examining the timecourses to the frequent and infrequent tones separately, RM-ANOVA with condition (frequent vs. rare), peak (N100m and N200m), and hemisphere as within-subject factors and diagnosis and sex as the between-subject factors showed a significant interaction of peak by diagnosis (p = 0.001), with a pattern of decreased amplitude from N100m to N200m in Control children and the opposite pattern in children with FASD. However, no significant difference was found with the simple effects comparisons. No group differences were found in the response latencies of the rare auditory evoked fields (AEFs). The results indicate that there was no detectable effect of alcohol exposure on the amplitude or latency of the MMNm response to simple tones modulated by frequency change in preschool-age children with FASD. However, while discrimination abilities to simple tones may be intact, early auditory sensory processing revealed by the interaction between N100m and N200m amplitude indicates that auditory sensory processing may be altered in

Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

International Nuclear Information System (INIS)

Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

1988-01-01

The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate [Gpp(NH)p] on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed [ 32 P]ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-α/sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-α/sub i/ or anti-α 0 antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed

New relations for graviton-matter amplitudes

CERN Multimedia

CERN. Geneva

2018-01-01

I report on recent progress in finding compact expressions for scattering amplitudes involving gravitons and gluons as well as massive scalar and fermionic matter particles. At tree level the single graviton emission amplitudes may be expressed as linear combination of purely non-gravitational ones. At the one-loop level recent results on all four point Einstein-Yang-Mills amplitudes with at most one opposite helicity state using unitarity methods are reported. 

Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography

International Nuclear Information System (INIS)

Claus, J.J.; Dubois, E.A.; Booij, J.; Habraken, J.; Munck, J.C. van; Herk, M. van; Verbeeten, B. Jr.; Royen, E.A. van

1997-01-01

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [ 123 I[4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [ 123 I[4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intra-observer variability was 3.6% and inter-observer results showed consistent differences in [ 123 I[4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [ 123 I[4-iododexetimide binding is reduced in patients with mild probable Alzheimer's disease in areas of temporal and temporo-parietal cortex. (orig.). With 1 fig., 4 tabs

One-loop triple collinear splitting amplitudes in QCD

Energy Technology Data Exchange (ETDEWEB)

Badger, Simon; Buciuni, Francesco; Peraro, Tiziano [Higgs Centre for Theoretical Physics, School of Physics and Astronomy, University of Edinburgh,Edinburgh EH9 3JZ, Scotland (United Kingdom)

2015-09-28

We study the factorisation properties of one-loop scattering amplitudes in the triple collinear limit and extract the universal splitting amplitudes for processes initiated by a gluon. The splitting amplitudes are derived from the analytic Higgs plus four partons amplitudes. We present compact results for primitive helicity splitting amplitudes making use of super-symmetric decompositions. The universality of the collinear factorisation is checked numerically against the full colour six parton squared matrix elements.

Preparation of an imaging agent for cerebral muscarinic acetylcholine receptor, (R,S)131I-QNB

International Nuclear Information System (INIS)

Ding Shiyu; Chen Zhengping; Ji Shuren; Lu Chunxiong; Zhou Xiang; Fang Ping; Wu Chunying; Wang Bocheng; Xiang Jingde; Lin Yansong

2003-01-01

The method to synthesize a high affinity muscarinic receptor antagonist (R,S)I-QNB[(R)-(-)-l-azabicyclo [2,2,2]oct-3-yl-(S)-(+)-α-hydroxy-α-(4-[127I]iodophenyl)-α-phenyl acetate] from 4-nitrobenzophenone with improvement compared to literatures was reported in this article. IR, MS and 1 HNMR characterized the final product. (R,S) 131 I-QNB was prepared using Cu(I) assisted iodine exchange labeling, and showed by TLC that the radiolabeling yield (RLY) was over 80%, and radiochemical purity (RCP) was over 95%. Stability of the labelled compound was also determined. It was found that (R,S) 131 I-QNB dried by nitrogen blowing can stay at 4-10 degree C for a week without change of RCP

Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy.

Science.gov (United States)

Jakubík, J; Janíčková, H; El-Fakahany, E E; Doležal, V

2011-03-01

Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5'-γ-thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M₂ muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [³⁵S]GTPγS and [³H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M₂ muscarinic acetylcholine receptor. Agonists displayed biphasic competition curves with the antagonist [³H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [³H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from G(i/o) G-proteins but only its dissociation from G(s/olf) G-proteins. These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of G(i/o) versus G(s/olf) G-proteins that are not identified by conventional GTPγS binding. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Why does the agonist [18F]FP-TZTP bind preferentially to the M2 muscarinic receptor?

International Nuclear Information System (INIS)

Ravasi, L.; Kiesewetter, D.O.; Shimoji, K.; Lucignani, G.; Eckelman, W.C.

2006-01-01

Preferential binding of FP-TZTP at the M 2 receptor in vivo led to investigation of [ 18 F]FP-TZTP as a potential PET tracer for Alzheimer's disease, in which a substantial reduction of M 2 receptors has been observed in autopsy studies. We hereby investigated in vitro the FP-TZTP behavior to further elucidate the properties of FP-TZTP that lead to its M 2 selectivity. Chinese hamster ovarian cells expressing the five subtypes of human muscarinic receptor as well as the wild type were harvested in culture to assess equilibrium binding. Specific binding was calculated by subtraction of non-specific binding from total binding. Internal specific binding was calculated by subtraction of external specific binding from the total specific binding. Saturation assays were also performed to calculate B max , K i , and IC 50 . In addition, equilibrium binding and dissociation kinetic studies were performed on rat brain tissue. Selected regions of interest were drawn on the digital autoradiograms and [ 18 F]FP-TZTP off-rates were determined by measurement of the rate of release into a buffer solution of [ 18 F]FP-TZTP from slide-bound cells that had been preincubated with [ 18 F]FP-TZTP. At equilibrium in vitro, M 2 subtype selectivity of [ 18 F]FP-TZTP was not evident. We demonstrated that ATP-dependent mechanisms are not responsible for FP-TZTP M 2 selectivity. In vitro off-rate studies from rat brain tissue showed that the off-rate of FP-TZTP varied with the percentage of M 2 subtype in the tissue region. The slower dissociation kinetics of FP-TZTP from M 2 receptors compared with the four other muscarinic receptor subtypes may be a factor in its M 2 selectivity. (orig.)

Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles—a TMS Study

Science.gov (United States)

Sale, Martin V.; Rogasch, Nigel C.; Nordstrom, Michael A.

2016-01-01

The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs. PMID:27014031

Muscarinic agonists and phorbol esters increase tyrosine phosphorylation of a 40-kilodalton protein in hippocampal slices

International Nuclear Information System (INIS)

Stratton, K.R.; Worley, P.F.; Huganir, R.L.; Baraban, J.M.

1989-01-01

The authors have used the hippocampal slice preparation to investigate the regulation of protein tyrosine phosphorylation in brain. After pharmacological treatment of intact slices, proteins were separated by electrophoresis, and levels of protein tyrosine phosphorylation were assessed by immunoblotting with specific anti-phosphotyrosine antibodies. Phorbol esters, activators of the serine- and threonine-phosphorylating enzyme protein kinase C, selectively increase tyrosine phosphorylation of a soluble protein with an apparent molecular mass of approximately 40 kilodaltons. Muscarinic agonists such as carbachol and oxotremorine M that strongly activate the inositol phospholipid system also increase tyrosine phosphorylation of this protein. Neurotransmitter activation of the inositol phospholipid system and protein kinase C appears to trigger a cascade leading to increased tyrosine phosphorylation

Short-term locomotor adaptation to a robotic ankle exoskeleton does not alter soleus Hoffmann reflex amplitude.

Science.gov (United States)

Kao, Pei-Chun; Lewis, Cara L; Ferris, Daniel P

2010-07-26

To improve design of robotic lower limb exoskeletons for gait rehabilitation, it is critical to identify neural mechanisms that govern locomotor adaptation to robotic assistance. Previously, we demonstrated soleus muscle recruitment decreased by approximately 35% when walking with a pneumatically-powered ankle exoskeleton providing plantar flexor torque under soleus proportional myoelectric control. Since a substantial portion of soleus activation during walking results from the stretch reflex, increased reflex inhibition is one potential mechanism for reducing soleus recruitment when walking with exoskeleton assistance. This is clinically relevant because many neurologically impaired populations have hyperactive stretch reflexes and training to reduce the reflexes could lead to substantial improvements in their motor ability. The purpose of this study was to quantify soleus Hoffmann (H-) reflex responses during powered versus unpowered walking. We tested soleus H-reflex responses in neurologically intact subjects (n=8) that had trained walking with the soleus controlled robotic ankle exoskeleton. Soleus H-reflex was tested at the mid and late stance while subjects walked with the exoskeleton on the treadmill at 1.25 m/s, first without power (first unpowered), then with power (powered), and finally without power again (second unpowered). We also collected joint kinematics and electromyography. When the robotic plantar flexor torque was provided, subjects walked with lower soleus electromyographic (EMG) activation (27-48%) and had concomitant reductions in H-reflex amplitude (12-24%) compared to the first unpowered condition. The H-reflex amplitude in proportion to the background soleus EMG during powered walking was not significantly different from the two unpowered conditions. These findings suggest that the nervous system does not inhibit the soleus H-reflex in response to short-term adaption to exoskeleton assistance. Future studies should determine if the

Generalized unitarity for N=4 super-amplitudes

Energy Technology Data Exchange (ETDEWEB)

Drummond, J.M.; Henn, J. [LAPTH, Université de Savoie, CNRS B.P. 110, F-74941 Annecy-le-Vieux Cedex (France); Korchemsky, G.P., E-mail: Gregory.Korchemsky@cea.fr [Institut de Physique Théorique, CEA Saclay, 91191 Gif-sur-Yvette Cedex (France); Sokatchev, E. [LAPTH, Université de Savoie, CNRS B.P. 110, F-74941 Annecy-le-Vieux Cedex (France)

2013-04-21

We develop a manifestly supersymmetric version of the generalized unitarity cut method for calculating scattering amplitudes in N=4 SYM theory. We illustrate the power of this method by computing the one-loop n-point NMHV super-amplitudes. The result confirms two conjectures which we made in Drummond, et al., [1]. Firstly, we derive the compact, manifestly dual superconformally covariant form of the NMHV tree amplitudes for arbitrary number and types of external particles. Secondly, we show that the ratio of the one-loop NMHV to the MHV amplitude is dual conformal invariant.

Scopolamine Reduces Electrophysiological Indices of Distractor Suppression: Evidence from a Contingent Capture Task

Directory of Open Access Journals (Sweden)

Inga Laube

2017-12-01

Full Text Available Limited resources for the in-depth processing of external stimuli make it necessary to select only relevant information from our surroundings and to ignore irrelevant stimuli. Attentional mechanisms facilitate this selection via top-down modulation of stimulus representations in the brain. Previous research has indicated that acetylcholine (ACh modulates this influence of attention on stimulus processing. However, the role of muscarinic receptors as well as the specific mechanism of cholinergic modulation remains unclear. Here we investigated the influence of ACh on feature-based, top-down control of stimulus processing via muscarinic receptors by using a contingent capture paradigm which specifically tests attentional shifts toward uninformative cue stimuli which display one of the target defining features In a double-blind, placebo controlled study we measured the impact of the muscarinic receptor antagonist scopolamine on behavioral and electrophysiological measures of contingent attentional capture. The results demonstrated all the signs of functional contingent capture, i.e., attentional shifts toward cued locations reflected in increased amplitudes of N1 and N2Pc components, under placebo conditions. However, scopolamine did not affect behavioral or electrophysiological measures of contingent capture. Instead, scopolamine reduced the amplitude of the distractor-evoked Pd component which has recently been associated with active suppression of irrelevant distractor information. The findings suggest a general cholinergic modulation of top-down control during distractor processing.

Holographic corrections to meson scattering amplitudes

Energy Technology Data Exchange (ETDEWEB)

Armoni, Adi; Ireson, Edwin, E-mail: 746616@swansea.ac.uk

2017-06-15

We compute meson scattering amplitudes using the holographic duality between confining gauge theories and string theory, in order to consider holographic corrections to the Veneziano amplitude and associated higher-point functions. The generic nature of such computations is explained, thanks to the well-understood nature of confining string backgrounds, and two different examples of the calculation in given backgrounds are used to illustrate the details. The effect we discover, whilst only qualitative, is re-obtainable in many such examples, in four-point but also higher point amplitudes.

Multi-leg one-loop gravity amplitudes from gauge theory

International Nuclear Information System (INIS)

Bern, Z.; Dixon, L.; Perelstein, M.; Rozowsky, J.S.

1999-01-01

By exploiting relations between gravity and gauge theories, we present two infinite sequences of one-loop n-graviton scattering amplitudes: the 'maximally helicity-violating' amplitudes in N = 8 supergravity, and the 'all-plus' helicity amplitudes in gravity with any minimally coupled massless matter content. The all-plus amplitudes correspond to self-dual field configurations and vanish in supersymmetric theories. We make use of the tree-level Kawai-Lewellen-Tye (KLT) relations between open and closed string theory amplitudes, which in the low-energy limit imply relations between gravity and gauge theory tree amplitudes. For n ≤ 6, we determine the all-plus amplitudes explicitly from their unitarity cuts. The KLT relations, applied to the cuts, allow us to extend to gravity a previously found 'dimension-shifting' relation between (the cuts of) the all-plus amplitudes in gauge theory and the maximally helicity-violating amplitudes in N = 4 super-Yang-Mills theory. The gravitational version of the relation lets us determine the n ≤ 6N = 8 supergravity amplitudes from the all-plus gravity amplitudes. We infer the two series of amplitudes for all n from their soft and collinear properties, which can also be derived from gauge theory using the KLT relations

Covariant amplitudes in Polyakov string theory

International Nuclear Information System (INIS)

Aoyama, H.; Dhar, A.; Namazie, M.A.

1986-01-01

A manifestly Lorentz-covariant and reparametrization-invariant procedure for computing string amplitudes using Polyakov's formulation is described. Both bosonic and superstring theories are dealt with. The computation of string amplitudes is greatly facilitated by this formalism. (orig.)

Complex amplitude reconstruction by iterative amplitude-phase retrieval algorithm with reference

Science.gov (United States)

Shen, Cheng; Guo, Cheng; Tan, Jiubin; Liu, Shutian; Liu, Zhengjun

2018-06-01

Multi-image iterative phase retrieval methods have been successfully applied in plenty of research fields due to their simple but efficient implementation. However, there is a mismatch between the measurement of the first long imaging distance and the sequential interval. In this paper, an amplitude-phase retrieval algorithm with reference is put forward without additional measurements or priori knowledge. It gets rid of measuring the first imaging distance. With a designed update formula, it significantly raises the convergence speed and the reconstruction fidelity, especially in phase retrieval. Its superiority over the original amplitude-phase retrieval (APR) method is validated by numerical analysis and experiments. Furthermore, it provides a conceptual design of a compact holographic image sensor, which can achieve numerical refocusing easily.

Changes in acetylcholine content, release and muscarinic receptors in rat hippocampus under cold stress

International Nuclear Information System (INIS)

Fatranska, M.; Budai, D.; Gulya, K; Kvetnansky, R.

1989-01-01

The aim was to study the mechanism of the previously established decrease in acetylcholine (ACh) concentration in the rat hippocampus under cold stress. Male rats were exposed for 14 days to cold (5 degree C) or kept (controls) at room temperature (24 degree C). Acetylcholine content, release and muscarinic receptor binding were investigated in the hippocampus. Cold exposure resulted in a decrease of ACh concentration in the dorsal hippocampus. Moreover, the potassium-evoked release of ACh from hippocampal slices was increased and an increase of maximal binding capacity of [ 3 H](-) quinuclidinyl benzilate in the dorsal hippocampus of cold exposed animals was also observed. Thus the decrease of hippocampal ACh concentration under cold exposure is probably due to its increased release. On balance then, our results demonstrate that cold stress in the rat induces significant activation of the hippocampal cholinergic system

Regional distribution of muscarinic acetylcholine receptors in the telencephalon of the pigeon (Columba livia f. domestica). [Use of TH-quinuclidinylbenzylate

Energy Technology Data Exchange (ETDEWEB)

Waechtler, K.

1985-01-01

The distribution of muscarinic acetylcholine receptors was studied autoradiographically in croystat sections of the pigeon telencephalon using TH-quinuclidinylbenzylate as a ligand. Highest receptor density was observed in the hyperstriatum ventrale, palaeostriatum augmentatum, septum, and parts of the archistriatum. In sites of known sensory input of neostriatum (field L) and ectostriatum low receptor binding was observed. Acetylcholinesterase distribution is in good agreement with the receptor picture only in the basal telencephalon. In the pallium differences in the pattern of these two components can be seen.

DVCS amplitude with kinematical twist-3 terms

International Nuclear Information System (INIS)

Radyushkin, A.V.; Weiss, C.

2000-01-01

The authors compute the amplitude of deeply virtual Compton scattering (DVCS) using the calculus of QCD string operators in coordinate representation. To restore the electromagnetic gauge invariance (transversality) of the twist-2 amplitude they include the operators of twist-3 which appear as total derivatives of twist-2 operators. The results are equivalent to a Wandzura-Wilczek approximation for twist-3 skewed parton distributions. They find that this approximation gives a finite result for the amplitude of a longitudinally polarized virtual photon, while the amplitude for transverse polarization is divergent, i.e., factorization breaks down in this term

Amplitude-Mode Dynamics of Polariton Condensates

International Nuclear Information System (INIS)

Brierley, R. T.; Littlewood, P. B.; Eastham, P. R.

2011-01-01

We study the stability of collective amplitude excitations in nonequilibrium polariton condensates. These excitations correspond to renormalized upper polaritons and to the collective amplitude modes of atomic gases and superconductors. They would be present following a quantum quench or could be created directly by resonant excitation. We show that uniform amplitude excitations are unstable to the production of excitations at finite wave vectors, leading to the formation of density-modulated phases. The physical processes causing the instabilities can be understood by analogy to optical parametric oscillators and the atomic Bose supernova.

Effects of strength training on mechanomyographic amplitude

International Nuclear Information System (INIS)

DeFreitas, Jason M; Beck, Travis W; Stock, Matt S

2012-01-01

The aim of the present study was to determine if the patterns of mechanomyographic (MMG) amplitude across force would change with strength training. Twenty-two healthy men completed an 8-week strength training program. During three separate testing visits (pre-test, week 4, and week 8), the MMG signal was detected from the vastus lateralis as the subjects performed isometric step muscle actions of the leg extensors from 10–100% of maximal voluntary contraction (MVC). During pre-testing, the MMG amplitude increased linearly with force to 66% MVC and then plateaued. Conversely, weeks 4 and 8 demonstrated an increase in MMG amplitude up to ∼85% of the subject's original MVC before plateauing. Furthermore, seven of the ten force levels (30–60% and 80–100%) showed a significant decrease in mean MMG amplitude values after training, which consequently led to a decrease in the slope of the MMG amplitude/force relationship. The decreases in MMG amplitude at lower force levels are indicative of hypertrophy, since fewer motor units would be required to produce the same absolute force if the motor units increased in size. However, despite the clear changes in the mean values, analyses of individual subjects revealed that only 55% of the subjects demonstrated a significant decrease in the slope of the MMG amplitude/force relationship. (paper)

Noninvasive quantification of muscarinic receptors in vivo with positron emission tomography in the dog heart

International Nuclear Information System (INIS)

Delforge, J.; Janier, M.; Syrota, A.; Crouzel, C.; Vallois, J.M.; Cayla, J.; Lancon, J.P.; Mazoyer, B.M.

1990-01-01

The in vivo quantification of myocardial muscarinic receptors has been obtained in six closed-chest dogs by using positron emission tomography. The dogs were injected with a trace amount of 11C-labeled methylquinuclidinyl benzilate (MQNB), a nonmetabolized antagonist of the muscarinic receptor. This was followed 30 minutes later by an injection of an excess of unlabeled MQNB (displacement experiment). Two additional injections of unlabeled MQNB with [11C]MQNB and without [11C]MQNB (second displacement experiment) were administered after 70 and 120 minutes, respectively. This protocol allowed a separate evaluation of the quantity of available receptors (B'max) as well as the association and dissociation rate constants (k+1 and k-1) in each dog. The parameters were calculated by using a nonlinear mathematical model in regions of interest over the left ventricle and the interventricular septum. The average value of B'max was 42 +/- 11 pmol/ml tissue, the rate constants k+1, k-1, and Kd were 0.6 +/- 0.1 ml.pmol-1.min-1, 0.27 +/- 0.03 ml.pmol-1.min-1, and 0.49 +/- 0.14 pmol.ml-1, respectively, taking into account the MQNB reaction volume estimated to 0.15 ml/ml tissue. Although [11C]MQNB binding would appear irreversible, our findings indicate that the association of the antagonist is very rapid and that the dissociation is far from negligible. The dissociated ligand, however, has a high probability of rebinding to a free receptor site instead of escaping into the microcirculation. We deduce that the positron emission tomographic images obtained after injecting a trace amount of [11C]MQNB are more representative of blood flow than of receptor density or affinity. We also suggest a simplified protocol consisting of a tracer injection of [11C]MQNB and a second injection of an excess of cold MQNB, which is sufficient to measure B'max and Kd in humans

Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

International Nuclear Information System (INIS)

Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.

1987-01-01

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. 45 Ca 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 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-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

Nonsinglet pentagons and NMHV amplitudes

Directory of Open Access Journals (Sweden)

A.V. Belitsky

2015-07-01

Full Text Available Scattering amplitudes in maximally supersymmetric gauge theory receive a dual description in terms of the expectation value of the super Wilson loop stretched on a null polygonal contour. This makes the analysis amenable to nonperturbative techniques. Presently, we elaborate on a refined form of the operator product expansion in terms of pentagon transitions to compute twist-two contributions to NMHV amplitudes. To start with, we provide a novel derivation of scattering matrices starting from Baxter equations for flux-tube excitations propagating on magnon background. We propose bootstrap equations obeyed by pentagon form factors with nonsinglet quantum numbers with respect to the R-symmetry group and provide solutions to them to all orders in 't Hooft coupling. These are then successfully confronted against available perturbative calculations for NMHV amplitudes to four-loop order.

Nonsinglet pentagons and NMHV amplitudes

Energy Technology Data Exchange (ETDEWEB)

Belitsky, A.V., E-mail: andrei.belitsky@asu.edu

2015-07-15

Scattering amplitudes in maximally supersymmetric gauge theory receive a dual description in terms of the expectation value of the super Wilson loop stretched on a null polygonal contour. This makes the analysis amenable to nonperturbative techniques. Presently, we elaborate on a refined form of the operator product expansion in terms of pentagon transitions to compute twist-two contributions to NMHV amplitudes. To start with, we provide a novel derivation of scattering matrices starting from Baxter equations for flux-tube excitations propagating on magnon background. We propose bootstrap equations obeyed by pentagon form factors with nonsinglet quantum numbers with respect to the R-symmetry group and provide solutions to them to all orders in 't Hooft coupling. These are then successfully confronted against available perturbative calculations for NMHV amplitudes to four-loop order.

Audio-Visual and Autogenic Relaxation Alter Amplitude of Alpha EEG Band, Causing Improvements in Mental Work Performance in Athletes.

Science.gov (United States)

Mikicin, Mirosław; Kowalczyk, Marek

2015-09-01

The aim of the present study was to investigate the effect of regular audio-visual relaxation combined with Schultz's autogenic training on: (1) the results of behavioral tests that evaluate work performance during burdensome cognitive tasks (Kraepelin test), (2) changes in classical EEG alpha frequency band, neocortex (frontal, temporal, occipital, parietal), hemisphere (left, right) versus condition (only relaxation 7-12 Hz). Both experimental (EG) and age-and skill-matched control group (CG) consisted of eighteen athletes (ten males and eight females). After 7-month training EG demonstrated changes in the amplitude of mean electrical activity of the EEG alpha bend at rest and an improvement was significantly changing and an improvement in almost all components of Kraepelin test. The same examined variables in CG were unchanged following the period without the intervention. Summing up, combining audio-visual relaxation with autogenic training significantly improves athlete's ability to perform a prolonged mental effort. These changes are accompanied by greater amplitude of waves in alpha band in the state of relax. The results suggest usefulness of relaxation techniques during performance of mentally difficult sports tasks (sports based on speed and stamina, sports games, combat sports) and during relax of athletes.

Amplitude ratios in ρ0 leptoproductions and GPDs

Directory of Open Access Journals (Sweden)

Goloskokov S.V.

2017-01-01

Using the model results we calculate the ratio of different helicity amplitudes for a transversely polarized proton target to the leading twist longitudinal amplitude. Our results are close to the amplitude ratios measured by HERMES.

Differential expression of muscarinic acetylcholine receptor subtypes in Jurkat cells and their signaling.

Science.gov (United States)

Alea, Mileidys Perez; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Fuxe, Kjell; Garriga, Pere

2011-08-15

Muscarinic acetylcholine receptors expression and signaling in the human Jurkat T cell line were investigated. Semiquantitative real-time PCR and radioligand binding studies, using a wide set of antagonist compounds, showed the co-existence of M(3), M(4), and M(5) subtypes. Stimulation of these subpopulations caused a concentration and time- dependent activation of second messengers and ERK signaling pathways, with a major contribution of the M(3) subtype in a G(q/11)-mediated response. In addition, we found that T-cell stimulation leads to increased expression of M(3) and M(5) both at transcriptional and protein levels in a PLC/PKCθ dependent manner. Our data clarifies the functional role of AChR subtypes in Jurkat cells and pave the way to future studies on the potential cross-talk among these subpopulations and their regulation of T lymphocytes immune function. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site

Directory of Open Access Journals (Sweden)

Marlet Martinez-Archundia

2012-01-01

Full Text Available The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS. Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand.

Tree-level gluon amplitudes on the celestial sphere

Science.gov (United States)

Schreiber, Anders Ø.; Volovich, Anastasia; Zlotnikov, Michael

2018-06-01

Pasterski, Shao and Strominger have recently proposed that massless scattering amplitudes can be mapped to correlators on the celestial sphere at infinity via a Mellin transform. We apply this prescription to arbitrary n-point tree-level gluon amplitudes. The Mellin transforms of MHV amplitudes are given by generalized hypergeometric functions on the Grassmannian Gr (4 , n), while generic non-MHV amplitudes are given by more complicated Gelfand A-hypergeometric functions.

Correlations for reduced-width amplitudes in 49V

International Nuclear Information System (INIS)

Chou, B.H.; Mitchell, G.E.; Bilpuch, E.G.; Westerfeldt, C.R.

1980-01-01

Measurement of the relative sign of inelastic proton-channel amplitudes permits the determination of amplitude correlations. Data were obtained for 45 5/2 + resonances in 49 V. Although the reduced widths in each channel followed a Porter-Thomas distribution, large amplitude correlations were observed. The results are compared with the reduced-width--amplitude distribution of Krieger and Porter. This is the first direct test of the Krieger-Porter distribution

Tree-level amplitudes and dual superconformal symmetry

Energy Technology Data Exchange (ETDEWEB)

Drummond, J M, E-mail: drummond@lapp.in2p3.fr [PH-TH Division, CERN, CH-1211, Geneva 23 (Switzerland); LAPTH, Universite de Savoie, CNRS, B.P. 110, F-74941 Annecy-le-Vieux Cedex (France)

2011-11-11

We review the structure of gauge theory scattering amplitudes at tree level and describe how a compact expression can be found which encodes all the tree-level amplitudes in the maximally supersymmetric N=4 theory. The expressions for the amplitudes reveal a dual superconformal symmetry. We describe how these ideas can be extended to leading singularities and the loop integrand in the planar theory and discuss the appearance of dual conformal symmetry in higher-dimensional gauge theories. This paper is an invited review for a special issue of Journal of Physics A: Mathematical and Theoretical devoted to 'Scattering amplitudes in gauge theories'. (review)

Scattering Amplitudes via Algebraic Geometry Methods

DEFF Research Database (Denmark)

Søgaard, Mads

Feynman diagrams. The study of multiloop scattering amplitudes is crucial for the new era of precision phenomenology at the Large Hadron Collider (LHC) at CERN. Loop-level scattering amplitudes can be reduced to a basis of linearly independent integrals whose coefficients are extracted from generalized...

Expansion of all multitrace tree level EYM amplitudes

Science.gov (United States)

Du, Yi-Jian; Feng, Bo; Teng, Fei

2017-12-01

In this paper, we investigate the expansion of tree level multitrace Einstein-Yang-Mills (EYM) amplitudes. First, we propose two types of recursive expansions of tree level EYM amplitudes with an arbitrary number of gluons, gravitons and traces by those amplitudes with fewer traces or/and gravitons. Then we give many support evidence, including proofs using the Cachazo-He-Yuan (CHY) formula and Britto-Cachazo-Feng-Witten (BCFW) recursive relation. As a byproduct, two types of generalized BCJ relations for multitrace EYM are further proposed, which will be useful in the BCFW proof. After one applies the recursive expansions repeatedly, any multitrace EYM amplitudes can be given in the Kleiss-Kuijf (KK) basis of tree level color ordered Yang-Mills (YM) amplitudes. Thus the Bern-Carrasco-Johansson (BCJ) numerators, as the expansion coefficients, for all multitrace EYM amplitudes are naturally constructed.

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

International Nuclear Information System (INIS)

Kobayashi, Haruo; Suzuki, Tadahiko; Sakamoto, Maki; Hashimoto, Wataru; Kashiwada, Keiko; Sato, Itaru; Akahori, Fumiaki; Satoh, Tetsuo

2007-01-01

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

Scattering amplitudes in four- and six-dimensional gauge theories

International Nuclear Information System (INIS)

Schuster, Theodor

2014-01-01

We study scattering amplitudes in quantum chromodynamics (QCD), N=4 super Yang-Mills (SYM) theory and the six-dimensional N=(1,1) SYM theory, focusing on the symmetries of and relations between the tree-level scattering amplitudes in these three gauge theories. We derive the tree level and one-loop color decomposition of an arbitrary QCD amplitude into primitive amplitudes. Furthermore, we derive identities spanning the null space among the primitive amplitudes. We prove that every color ordered tree amplitude of massless QCD can be obtained from gluon-gluino amplitudes of N=4 SYM theory. Furthermore, we derive analytical formulae for all gluon-gluino amplitudes relevant for QCD. We compare the numerical efficiency and accuracy of evaluating these closed analytic formulae for color ordered QCD tree amplitudes to a numerically efficient implementation of the Berends-Giele recursion. We derive the symmetries of massive tree amplitudes on the coulomb branch of N=4 SYM theory, which in turn can be obtained from N=(1,1) SYM theory by dimensional reduction. Furthermore, we investigate the tree amplitudes of N=(1, 1) SYM theory and explain how analytical formulae can be obtained from a numerical implementation of the supersymmetric BCFW recursion relation and investigate a potential uplift of the massless tree amplitudes of N=4 SYM theory. Finally we study an alternative to dimensional regularization of N=4 SYM theory. The infrared divergences are regulated by masses obtained from a Higgs mechanism. The corresponding string theory set-up suggests that the amplitudes have an exact dual conformal symmetry. We confirm this expectation and illustrate the calculational advantages of the massive regulator by explicit calculations.

Positivity of spin foam amplitudes

International Nuclear Information System (INIS)

Baez, John C; Christensen, J Daniel

2002-01-01

The amplitude for a spin foam in the Barrett-Crane model of Riemannian quantum gravity is given as a product over its vertices, edges and faces, with one factor of the Riemannian 10j symbols appearing for each vertex, and simpler factors for the edges and faces. We prove that these amplitudes are always nonnegative for closed spin foams. As a corollary, all open spin foams going between a fixed pair of spin networks have real amplitudes of the same sign. This means one can use the Metropolis algorithm to compute expectation values of observables in the Riemannian Barrett-Crane model, as in statistical mechanics, even though this theory is based on a real-time (e iS ) rather than imaginary-time e -S path integral. Our proof uses the fact that when the Riemannian 10j symbols are nonzero, their sign is positive or negative depending on whether the sum of the ten spins is an integer or half-integer. For the product of 10j symbols appearing in the amplitude for a closed spin foam, these signs cancel. We conclude with some numerical evidence suggesting that the Lorentzian 10j symbols are always nonnegative, which would imply similar results for the Lorentzian Barrett-Crane model

Employing helicity amplitudes for resummation

International Nuclear Information System (INIS)

Moult, Ian; Stewart, Iain W.; Tackmann, Frank J.; Waalewijn, Wouter J.; Amsterdam Univ.

2015-08-01

Many state-of-the-art QCD calculations for multileg processes use helicity amplitudes as their fundamental ingredients. We construct a simple and easy-to-use helicity operator basis in soft-collinear effective theory (SCET), for which the hard Wilson coefficients from matching QCD onto SCET are directly given in terms of color-ordered helicity amplitudes. Using this basis allows one to seamlessly combine fixed-order helicity amplitudes at any order they are known with a resummation of higher-order logarithmic corrections. In particular, the virtual loop amplitudes can be employed in factorization theorems to make predictions for exclusive jet cross sections without the use of numerical subtraction schemes to handle real-virtual infrared cancellations. We also discuss matching onto SCET in renormalization schemes with helicities in 4- and d-dimensions. To demonstrate that our helicity operator basis is easy to use, we provide an explicit construction of the operator basis, as well as results for the hard matching coefficients, for pp → H+0,1,2 jets, pp → W/Z/γ+0,1,2 jets, and pp → 2,3 jets. These operator bases are completely crossing symmetric, so the results can easily be applied to processes with e + e - and e - p collisions.

An anti-nicotinic cognitive challenge model using mecamylamine in comparison with the anti-muscarinic cognitive challenge using scopolamine.

Science.gov (United States)

Baakman, Anne Catrien; Alvarez-Jimenez, Ricardo; Rissmann, Robert; Klaassen, Erica S; Stevens, Jasper; Goulooze, Sebastiaan C; den Burger, Jeroen C G; Swart, Eleonora L; van Gerven, Joop M A; Groeneveld, Geert Jan

2017-08-01

The muscarinic acetylcholine receptor antagonist scopolamine is often used for proof-of-pharmacology studies with pro-cognitive compounds. From a pharmacological point of view, it would seem more rational to use a nicotinic rather than a muscarinic anticholinergic challenge to prove pharmacology of a nicotinic acetylcholine receptor agonist. This study aims to characterize a nicotinic anticholinergic challenge model using mecamylamine and to compare it to the scopolamine model. In this double-blind, placebo-controlled, four-way cross-over trial, 12 healthy male subjects received oral mecamylamine 10 and 20 mg, intravenous scopolamine 0.5 mg and placebo. Pharmacokinetics were analysed using non-compartmental analysis. Pharmacodynamic effects were measured with a multidimensional test battery that includes neurophysiological, subjective, (visuo)motor and cognitive measurements. All treatments were safe and well tolerated. Mecamylamine had a t max of 2.5 h and a C max of 64.5 ng ml -1 for the 20 mg dose. Mecamylamine had a dose-dependent effect decreasing the adaptive tracking performance and VAS alertness, and increasing the finger tapping and visual verbal learning task performance time and errors. Scopolamine significantly affected almost all pharmacodynamic tests. This study demonstrated that mecamylamine causes nicotinic receptor specific temporary decline in cognitive functioning. Compared with the scopolamine model, pharmacodynamic effects were less pronounced at the dose levels tested; however, mecamylamine caused less sedation. The cognitive effects of scopolamine might at least partly be caused by sedation. Whether the mecamylamine model can be used for proof-of-pharmacology of nicotinic acetylcholine receptor agonists remains to be established. © 2017 The British Pharmacological Society.

Fatigue life prediction of rotor blade composites: Validation of constant amplitude formulations with variable amplitude experiments

International Nuclear Information System (INIS)

Westphal, T; Nijssen, R P L

2014-01-01

The effect of Constant Life Diagram (CLD) formulation on the fatigue life prediction under variable amplitude (VA) loading was investigated based on variable amplitude tests using three different load spectra representative for wind turbine loading. Next to the Wisper and WisperX spectra, the recently developed NewWisper2 spectrum was used. Based on these variable amplitude fatigue results the prediction accuracy of 4 CLD formulations is investigated. In the study a piecewise linear CLD based on the S-N curves for 9 load ratios compares favourably in terms of prediction accuracy and conservativeness. For the specific laminate used in this study Boerstra's Multislope model provides a good alternative at reduced test effort

Fatigue life prediction of rotor blade composites: Validation of constant amplitude formulations with variable amplitude experiments

Science.gov (United States)

Westphal, T.; Nijssen, R. P. L.

2014-12-01

The effect of Constant Life Diagram (CLD) formulation on the fatigue life prediction under variable amplitude (VA) loading was investigated based on variable amplitude tests using three different load spectra representative for wind turbine loading. Next to the Wisper and WisperX spectra, the recently developed NewWisper2 spectrum was used. Based on these variable amplitude fatigue results the prediction accuracy of 4 CLD formulations is investigated. In the study a piecewise linear CLD based on the S-N curves for 9 load ratios compares favourably in terms of prediction accuracy and conservativeness. For the specific laminate used in this study Boerstra's Multislope model provides a good alternative at reduced test effort.

Scattering Amplitudes via Algebraic Geometry Methods

CERN Document Server

Søgaard, Mads; Damgaard, Poul Henrik

This thesis describes recent progress in the understanding of the mathematical structure of scattering amplitudes in quantum field theory. The primary purpose is to develop an enhanced analytic framework for computing multiloop scattering amplitudes in generic gauge theories including QCD without Feynman diagrams. The study of multiloop scattering amplitudes is crucial for the new era of precision phenomenology at the Large Hadron Collider (LHC) at CERN. Loop-level scattering amplitudes can be reduced to a basis of linearly independent integrals whose coefficients are extracted from generalized unitarity cuts. We take advantage of principles from algebraic geometry in order to extend the notion of maximal cuts to a large class of two- and three-loop integrals. This allows us to derive unique and surprisingly compact formulae for the coefficients of the basis integrals. Our results are expressed in terms of certain linear combinations of multivariate residues and elliptic integrals computed from products of ...

Effective string theory and QCD scattering amplitudes

International Nuclear Information System (INIS)

Makeenko, Yuri

2011-01-01

QCD string is formed at distances larger than the confinement scale and can be described by the Polchinski-Strominger effective string theory with a nonpolynomial action, which has nevertheless a well-defined semiclassical expansion around a long-string ground state. We utilize modern ideas about the Wilson-loop/scattering-amplitude duality to calculate scattering amplitudes and show that the expansion parameter in the effective string theory is small in the Regge kinematical regime. For the amplitudes we obtain the Regge behavior with a linear trajectory of the intercept (d-2)/24 in d dimensions, which is computed semiclassically as a momentum-space Luescher term, and discuss an application to meson scattering amplitudes in QCD.

Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

1995-01-01

stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p basal and vagally stimulated PGE2 output increased significantly (p ...The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p basal and vagally...

Constructing QCD one-loop amplitudes

International Nuclear Information System (INIS)

Forde, D

2008-01-01

In the context of constructing one-loop amplitudes using a unitarity bootstrap approach we discuss a general systematic procedure for obtaining the coefficients of the scalar bubble and triangle integral functions of one-loop amplitudes. Coefficients are extracted after examining the behavior of the cut integrand as the unconstrained parameters of a specifically chosen parameterization of the cut loop momentum approach infinity. Measurements of new physics at the forthcoming experimental program at CERN's Large Hadron Collider (LHC) will require a precise understanding of processes at next-to-leading order (NLO). This places increased demands for the computation of new one-loop amplitudes. This in turn has spurred recent developments towards improved calculational techniques. Direct calculations using Feynman diagrams are in general inefficient. Developments of more efficient techniques have usually centered around unitarity techniques [1], where tree amplitudes are effectively 'glued' together to form loops. The most straightforward application of this method, in which the cut loop momentum is in D = 4, allows for the computation of 'cut-constructible' terms only, i.e. (poly)logarithmic containing terms and any related constants. QCD amplitudes contain, in addition to such terms, rational pieces which cannot be derived using such cuts. These 'missing' rational parts can be extracted using cut loop momenta in D = 4-2 (var e psilon). The greater difficulty of such calculations has restricted the application of this approach, although recent developments [3, 4] have provided new promise for this technique. Recently the application of on-shell recursion relations [5] to obtaining the 'missing' rational parts of one-loop processes [6] has provided an alternative very promising solution to this problem. In combination with unitarity methods an 'on-shell bootstrap' approach provides an efficient technique for computing complete one-loop QCD amplitudes [7]. Additionally

Phonological awareness and sinusoidal amplitude modulation in phonological dislexia.

Science.gov (United States)

Peñaloza-López, Yolanda; Herrera-Rangel, Aline; Pérez-Ruiz, Santiago J; Poblano, Adrián

2016-04-01

Dyslexia is the difficulty of children in learning to read and write as results of neurological deficiencies. The objective was to test the Phonological awareness (PA) and Sinusoidal amplitude modulation (SAM) threshold in children with Phonological dyslexia (PD). We performed a case-control, analytic, cross sectional study. We studied 14 children with PD and 14 control children from 7 to 11 years of age, by means of PA measurement and by SAM test. The mean age of dyslexic children was 8.39 years and in the control group was 8.15. Children with PD exhibited inadequate skills in PA, and SAM. We found significant correlations between PA and SAM at 4 Hertz frequency, and calculated regression equations that predicts between one-fourth and one-third of variance of measurements. Alterations in PA and SAM found can help to explain basis of deficient language processing exhibited by children with PD.

High energy hadron spin-flip amplitude

International Nuclear Information System (INIS)

Selyugin, O.V.

2016-01-01

The high-energy part of the hadron spin-flip amplitude is examined in the framework of the new high-energy general structure (HEGS) model of the elastic hadron scattering at high energies. The different forms of the hadron spin-flip amplitude are compared in the impact parameter representation. It is shown that the existing experimental data of the proton-proton and proton-antiproton elastic scattering at high energy in the region of the diffraction minimum and at large momentum transfer give support in the presence of the energy-independent part of the hadron spin-flip amplitude with the momentum dependence proposed in the works by Galynskii-Kuraev. [ru

Hidden simplicity of gauge theory amplitudes

Energy Technology Data Exchange (ETDEWEB)

Drummond, J M, E-mail: drummond@lapp.in2p3.f [LAPTH, Universite de Savoie, CNRS, B.P. 110, F-74941 Annecy-le-Vieux, Cedex (France)

2010-11-07

These notes were given as lectures at the CERN Winter School on Supergravity, Strings and Gauge Theory 2010. We describe the structure of scattering amplitudes in gauge theories, focussing on the maximally supersymmetric theory to highlight the hidden symmetries which appear. Using the Britto, Cachzo, Feng and Witten (BCFW) recursion relations we solve the tree-level S-matrix in N=4 super Yang-Mills theory and describe how it produces a sum of invariants of a large symmetry algebra. We review amplitudes in the planar theory beyond tree level, describing the connection between amplitudes and Wilson loops, and discuss the implications of the hidden symmetries.

On the singularities of massive superstring amplitudes

Energy Technology Data Exchange (ETDEWEB)

Foda, O.

1987-06-04

Superstring one-loop amplitudes with massive external states are shown to be in general ill-defined due to internal on-shell propagators. However, we argue that since any massive string state (in the uncompactified theory) has a finite lifetime to decay into massless particles, such amplitudes are not terms in the perturbative expansion of physical S-matrix elements: These can be defined only with massless external states. Consistent massive amplitudes repuire an off-shell formalism.

Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine-mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception.

Science.gov (United States)

de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Biagioni, Audrey Franceschi; Falconi-Sobrinho, Luiz Luciano; Dos Anjos-Garcia, Tayllon; Coimbra, Norberto Cysne

2016-10-01

Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1μg, 3μg and 5μg/0.2μL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail-flick test. Pre-treatment of the LC with 1μg, 3μg and 5μg/0.2μL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception. Copyright © 2016 Elsevier Inc. All rights reserved.

Asparagine, valine, and threonine in the third extracellular loop of muscarinic receptor have essential roles in the positive cooperativity of strychnine-like allosteric modulators

Czech Academy of Sciences Publication Activity Database

Jakubík, Jan; Krejčí, Alena; Doležal, Vladimír

2005-01-01

Roč. 313, č. 2 (2005), s. 688-696 ISSN 0022-3565 R&D Projects: GA ČR(CZ) GA309/02/1331; GA ČR(CZ) GP305/02/D090; GA AV ČR(CZ) IAA5011306; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic receptors * positive cooperativity * mutation Subject RIV: ED - Physiology Impact factor: 4.098, year: 2005

Nonlinear (super)symmetries and amplitudes

Energy Technology Data Exchange (ETDEWEB)

Kallosh, Renata [Physics Department, Stanford University,382 Via Pueblo Mall, Stanford, CA 94305-4060 (United States)

2017-03-07

There is an increasing interest in nonlinear supersymmetries in cosmological model building. Independently, elegant expressions for the all-tree amplitudes in models with nonlinear symmetries, like D3 brane Dirac-Born-Infeld-Volkov-Akulov theory, were recently discovered. Using the generalized background field method we show how, in general, nonlinear symmetries of the action, bosonic and fermionic, constrain amplitudes beyond soft limits. The same identities control, for example, bosonic E{sub 7(7)} scalar sector symmetries as well as the fermionic goldstino symmetries. We present a universal derivation of the vanishing amplitudes in the single (bosonic or fermionic) soft limit. We explain why, universally, the double-soft limit probes the coset space algebra. We also provide identities describing the multiple-soft limit. We discuss loop corrections to N≥5 supergravity, to the D3 brane, and the UV completion of constrained multiplets in string theory.

Cluster polylogarithms for scattering amplitudes

International Nuclear Information System (INIS)

Golden, John; Paulos, Miguel F; Spradlin, Marcus; Volovich, Anastasia

2014-01-01

Motivated by the cluster structure of two-loop scattering amplitudes in N=4 Yang-Mills theory we define cluster polylogarithm functions. We find that all such functions of weight four are made up of a single simple building block associated with the A 2 cluster algebra. Adding the requirement of locality on generalized Stasheff polytopes, we find that these A 2 building blocks arrange themselves to form a unique function associated with the A 3 cluster algebra. This A 3 function manifests all of the cluster algebraic structure of the two-loop n-particle MHV amplitudes for all n, and we use it to provide an explicit representation for the most complicated part of the n = 7 amplitude as an example. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Cluster algebras in mathematical physics’. (paper)

Eikonal representation of N-body Coulomb scattering amplitudes

International Nuclear Information System (INIS)

Fried, H.M.; Kang, K.; McKellar, B.H.J.

1983-01-01

A new technique for the construction of N-body Coulomb scattering amplitudes is proposed, suggested by the simplest case of N = 2: Calculate the scattering amplitude in eikonal approximation, discard the infinite phase factors which appear upon taking the limit of a Coulomb potential, and treat the remainder as an amplitude whose absolute value squared produces the exact, Coulomb differential cross section. The method easily generalizes to the N-body Coulomb problem for elastic scattering, and for inelastic rearrangement scattering of Coulomb bound states. We give explicit results for N = 3 and 4; in the N = 3 case we extract amplitudes for the processes (12)+3->1+2+3 (breakup), (12)+3->1+(23) (rearrangement), and (12)+3→(12)'+3 (inelastic scattering) as residues at the appropriate poles in the free-free amplitude. The method produces scattering amplitudes f/sub N/ given in terms of explicit quadratures over (N-2) 2 distinct integrands

Different stimulation frequencies alter synchronous fluctuations in motor evoked potential amplitude of intrinsic hand muscles – a TMS study.

Directory of Open Access Journals (Sweden)

Martin Victor Sale

2016-03-01

Full Text Available The amplitude of motor-evoked potentials (MEPs elicited with transcranial magnetic stimulation (TMS varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic rates, and compared this with pseudo-random (aperiodic timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz and one aperiodic frequency (mean 0.2 Hz. MEPs (n = 50 were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

Geochemical behaviour of uranium in the cycle of alteration

International Nuclear Information System (INIS)

Chervet, J.; Coulomb, R.

1958-01-01

The investigation of the genesis of secondary mineralized accumulations, and the prospecting of deposits from microchemical anomalies in the surface material, is requiring a well-developed knowledge of the geochemical properties of the uranium during the alteration phase. In the present work, the authors tried to track the uranium history during a part of his natural creeping. a) They describe some most typical mineralogical observations of alteration phenomena and material migration, picked up in place on the deposits. b) They give experimental results concerning the solubilities of the uranium minerals and the factors affecting this solubility. c) They study the water circulation in granitic batholites, and the influence of the occurrence of the uranium deposits on their composition. d) They observe the amplitude of phenomena restricting the dispersions: fixations, precipitations, etc., and the behaviour of growth in uraniferous areas. e) Finally, the opposition chemical alteration-radioactive equilibrium results in an important imbalance in altered materials. The authors tried to use the measurement of this imbalance to explain geochemical processes. (author) [fr

New rigorous asymptotic theorems for inverse scattering amplitudes

International Nuclear Information System (INIS)

Lomsadze, Sh.Yu.; Lomsadze, Yu.M.

1984-01-01

The rigorous asymptotic theorems both of integral and local types obtained earlier and establishing logarithmic and in some cases even power correlations aetdeen the real and imaginary parts of scattering amplitudes Fsub(+-) are extended to the inverse amplitudes 1/Fsub(+-). One also succeeds in establishing power correlations of a new type between the real and imaginary parts, both for the amplitudes themselves and for the inverse ones. All the obtained assertions are convenient to be tested in high energy experiments when the amplitudes show asymptotic behaviour

On the singularities of massive superstring amplitudes

International Nuclear Information System (INIS)

Foda, O.

1987-01-01

Superstring one-loop amplitudes with massive external states are shown to be in general ill-defined due to internal on-shell propagators. However, we argue that since any massive string state (in the uncompactified theory) has a finite lifetime to decay into massless particles, such amplitudes are not terms in the perturbative expansion of physical S-matrix elements: These can be defined only with massless external states. Consistent massive amplitudes repuire an off-shell formalism. (orig.)

Pirenzepine block of ACh-induced mucus secretion in tracheal submucosal gland cells

International Nuclear Information System (INIS)

Farley, J.M.; Dwyer, T.M.

1991-01-01

Muscarinic stimulation of mucus secretion, as measured by the release of [ 3 H]glycoprotein, was studied in explants from the tracheal epithelium of weanling swine. The mucus glycoprotein secretion was transient, ceasing within the first 10 min of a continuous exposure to 100 μM ACh. Increasing the solutions' osmotic pressure did not alter basal mucus glycoprotein secretion. Mucus glycoprotein secretion was inhibited by 2-10 μM PZP, indicting that the M 3 muscarinic receptors mediate cholinergic stimulation of mucus production

Evidence for cholinergic participation in the control of bird song; acetylcholinesterase distribution and muscarinic receptor autoradiography in the zebra finch brain

International Nuclear Information System (INIS)

Ryan, S.M.; Arnold, A.P.

1981-01-01

Brain regions thought to be involved in the control of song in the zebra finch (Poephila guttata), were examined histochemically using the Karnovsky and Roots direct-coloring method for the detection of acetylcholinesterase (AChE) and the autoradiographic method for the localization of muscarinic cholinergic receptors following injection of tritiated quinuclidinyl benzilate (3H QNB). All presently identified vocal control nuclei in both males and females contain AChE. These nuclei include Area X, magnocellular nucleus of the anterior neostriatum (MAN), nucleus interface (NIF), caudal nucleus of the hyperstriatum ventrale (HVc), intercollicular nucleus (ICo), nucleus uva, robust nucleus of the archistriatum (RA), and tracheosyringeal portion of the hypoglossal nerve nucleus (nXIIts). All nuclei except Area X contain mostly AChE-synthesizing cell bodies. All of these nuclei contain some AChE in the neuropil, with particularly intense staining in Area X, the surrounding LPO, and the dorsomedial portion of ICo. In agreement with this description are very high concentrations of 3H QNB in both Area X and the dorsomedial ICo. HVc also appears specifically labeled. Evidence from these two histological technique suggests that efferent projections of most vocal control area may utilize acetylcholine, and that several of the vocal control nuclei may themselves receive muscarinic cholinergic projection. In Area X, there are sex differences of AChE neuropil staining. This evidence suggesting that sexually dimorphic projections to or within Area X are cholinergic or cholinoceptive

Corrections to the large-angle scattering amplitude

International Nuclear Information System (INIS)

Goloskokov, S.V.; Kudinov, A.V.; Kuleshov, S.P.

1979-01-01

High-energy behaviour of scattering amplitudes is considered within the frames of Logunov-Tavchelidze quasipotential approach. The representation of scattering amplitude of two scalar particles, convenient for the study of its asymptotic properties is given. Obtained are corrections of the main value of scattering amplitude of the first and the second orders in 1/p, where p is the pulse of colliding particles in the system of the inertia centre. An example of the obtained formulas use for a concrete quasipotential is given

Helicity amplitudes for matter-coupled gravity

International Nuclear Information System (INIS)

Aldrovandi, R.; Novaes, S.F.; Spehler, D.

1992-07-01

The Weyl-van der Waerden spinor formalism is applied to the evaluation of helicity invariant amplitudes in the framework of linearized gravitation. The graviton couplings to spin-0, 1 - 2 , 1, and 3 - 2 particles are given, and, to exhibit the reach of this method, the helicity amplitudes for the process electron + positron → photon + graviton are obtained. (author)

GSC4813-0981 = V921 Mon, a new low-amplitude δ Scuti star with variable amplitude

Science.gov (United States)

Galeev, A.; Bikmaev, I.; Shimansky, V.; Deminova, N.

2014-11-01

GSC 4813-0981 = V921 Mon is a low-amplitude δ Scuti-type variable with an amplitude of 0.018^m-0.027^m in different bands and a period of 48.5 minutes. The fundamental parameters of the atmosphere and physical characteristics, determined from medium-resolution spectra, are: T_{eff}=8700 K, log g=3.95 dex, [M/H]=0, M=1.7 M_{⊙}, R=2.3 R_{⊙}. We performed a long-term analysis of the variations using a ten-year data set of CCD observations (2003-2013) acquired in BVR with the 1.5-m Russian-Turkish telescope (RTT150, TUBITAK National Observatory). A preliminary result is that the amplitude of the variability changes; it was decreasing during 2003-2008, but is now increasing.

Fringe image analysis based on the amplitude modulation method.

Science.gov (United States)

Gai, Shaoyan; Da, Feipeng

2010-05-10

A novel phase-analysis method is proposed. To get the fringe order of a fringe image, the amplitude-modulation fringe pattern is carried out, which is combined with the phase-shift method. The primary phase value is obtained by a phase-shift algorithm, and the fringe-order information is encoded in the amplitude-modulation fringe pattern. Different from other methods, the amplitude-modulation fringe identifies the fringe order by the amplitude of the fringe pattern. In an amplitude-modulation fringe pattern, each fringe has its own amplitude; thus, the order information is integrated in one fringe pattern, and the absolute fringe phase can be calculated correctly and quickly with the amplitude-modulation fringe image. The detailed algorithm is given, and the error analysis of this method is also discussed. Experimental results are presented by a full-field shape measurement system where the data has been processed using the proposed algorithm. (c) 2010 Optical Society of America.

MHV Vertices And Tree Amplitudes In Gauge Theory

International Nuclear Information System (INIS)

Cachazo, Freddy; Svrcek, Peter; Witten, Edward

2004-01-01

As an alternative to the usual Feynman graphs, tree amplitudes in Yang-Mills theory can be constructed from tree graphs in which the vertices are tree level MHV scattering amplitudes, continued off shell in a particular fashion. The formalism leads to new and relatively simple formulas for many amplitudes, and can be heuristically derived from twistor space. (author)

Scattering amplitudes in gauge theories

Energy Technology Data Exchange (ETDEWEB)

Henn, Johannes M. [Institute for Advanced Study, Princeton, NJ (United States). School of Natural Sciences; Plefka, Jan C. [Humboldt-Universitaet, Berlin (Germany). Inst. fuer Physik

2014-03-01

First monographical text on this fundamental topic. Course-tested, pedagogical and self-contained exposition. Includes exercises and solutions. At the fundamental level, the interactions of elementary particles are described by quantum gauge field theory. The quantitative implications of these interactions are captured by scattering amplitudes, traditionally computed using Feynman diagrams. In the past decade tremendous progress has been made in our understanding of and computational abilities with regard to scattering amplitudes in gauge theories, going beyond the traditional textbook approach. These advances build upon on-shell methods that focus on the analytic structure of the amplitudes, as well as on their recently discovered hidden symmetries. In fact, when expressed in suitable variables the amplitudes are much simpler than anticipated and hidden patterns emerge. These modern methods are of increasing importance in phenomenological applications arising from the need for high-precision predictions for the experiments carried out at the Large Hadron Collider, as well as in foundational mathematical physics studies on the S-matrix in quantum field theory. Bridging the gap between introductory courses on quantum field theory and state-of-the-art research, these concise yet self-contained and course-tested lecture notes are well-suited for a one-semester graduate level course or as a self-study guide for anyone interested in fundamental aspects of quantum field theory and its applications. The numerous exercises and solutions included will help readers to embrace and apply the material presented in the main text.

Scattering amplitudes in gauge theories

International Nuclear Information System (INIS)

Henn, Johannes M.; Plefka, Jan C.

2014-01-01

First monographical text on this fundamental topic. Course-tested, pedagogical and self-contained exposition. Includes exercises and solutions. At the fundamental level, the interactions of elementary particles are described by quantum gauge field theory. The quantitative implications of these interactions are captured by scattering amplitudes, traditionally computed using Feynman diagrams. In the past decade tremendous progress has been made in our understanding of and computational abilities with regard to scattering amplitudes in gauge theories, going beyond the traditional textbook approach. These advances build upon on-shell methods that focus on the analytic structure of the amplitudes, as well as on their recently discovered hidden symmetries. In fact, when expressed in suitable variables the amplitudes are much simpler than anticipated and hidden patterns emerge. These modern methods are of increasing importance in phenomenological applications arising from the need for high-precision predictions for the experiments carried out at the Large Hadron Collider, as well as in foundational mathematical physics studies on the S-matrix in quantum field theory. Bridging the gap between introductory courses on quantum field theory and state-of-the-art research, these concise yet self-contained and course-tested lecture notes are well-suited for a one-semester graduate level course or as a self-study guide for anyone interested in fundamental aspects of quantum field theory and its applications. The numerous exercises and solutions included will help readers to embrace and apply the material presented in the main text.

Conformal higher spin scattering amplitudes from twistor space

Energy Technology Data Exchange (ETDEWEB)

Adamo, Tim [Blackett Laboratory, Imperial College, London, SW7 2AZ (United Kingdom); Hähnel, Philipp; McLoughlin, Tristan [School of Mathematics, Trinity College Dublin, College Green, Dublin 2 (Ireland)

2017-04-04

We use the formulation of conformal higher spin (CHS) theories in twistor space to study their tree-level scattering amplitudes, finding expressions for all three-point (MHV)-bar amplitudes and all MHV amplitudes involving positive helicity conformal gravity particles and two negative helicity higher spins. This provides the on-shell analogue for the covariant coupling of CHS fields to a conformal gravity background. We discuss the restriction of the theory to a ghost-free unitary subsector, analogous to restricting conformal gravity to general relativity with a cosmological constant. We study the flat-space limit and show that the restricted amplitudes vanish, supporting the conjecture that in the unitary sector the S-matrix of CHS theories is trivial. However, by appropriately rescaling the amplitudes we find non-vanishing results which we compare with chiral flat-space higher spin theories.

Conformal higher spin scattering amplitudes from twistor space

International Nuclear Information System (INIS)

Adamo, Tim; Hähnel, Philipp; McLoughlin, Tristan

2017-01-01

We use the formulation of conformal higher spin (CHS) theories in twistor space to study their tree-level scattering amplitudes, finding expressions for all three-point (MHV)-bar amplitudes and all MHV amplitudes involving positive helicity conformal gravity particles and two negative helicity higher spins. This provides the on-shell analogue for the covariant coupling of CHS fields to a conformal gravity background. We discuss the restriction of the theory to a ghost-free unitary subsector, analogous to restricting conformal gravity to general relativity with a cosmological constant. We study the flat-space limit and show that the restricted amplitudes vanish, supporting the conjecture that in the unitary sector the S-matrix of CHS theories is trivial. However, by appropriately rescaling the amplitudes we find non-vanishing results which we compare with chiral flat-space higher spin theories.

Amplitude-to-frequency converter of radioisotope instruments

International Nuclear Information System (INIS)

Demchenkov, V.P.; Korobkov, I.N.

1988-01-01

An amplitude-to-frequency converter designed for signal processing of radioisotope relay devices is descibed. The basic elements of the converter are a scaling amplifier, an analog-to-digital converter, a code-to-frequency converter, a null-organ, a delay unit and a clock-pulse generator. The designed amplitude-to-frequency converter takes into account a prior information about the signal shape of the energy spectrum. The converter processes input pulses of 0.10 V amplitude and duration more than 2μs. The energy channel number is 64

Amplitude-modulated fiber-ring laser

DEFF Research Database (Denmark)

Caputo, J. G.; Clausen, Carl A. Balslev; Sørensen, Mads Peter

2000-01-01

Soliton pulses generated by a fiber-ring laser are investigated by numerical simulation and perturbation methods. The mathematical modeling is based on the nonlinear Schrödinger equation with perturbative terms. We show that active mode locking with an amplitude modulator leads to a self......-starting of stable solitonic pulses from small random noise, provided the modulation depth is small. The perturbative analysis leads to a nonlinear coupled return map for the amplitude, phase, and position of the soliton pulses circulating in the fiber-ring laser. We established the validity of this approach...

The five-gluon amplitude and one-loop integrals

International Nuclear Information System (INIS)

Bern, Z.; Dixon, L.; Kosower, D.A.

1992-12-01

We review the conventional field theory description of the string motivated technique. This technique is applied to the one-loop five-gluon amplitude. To evaluate the amplitude a general method for computing dimensionally regulated one-loop integrals is outlined including results for one-loop integrals required for the pentagon diagram and beyond. Finally, two five-gluon helicity amplitudes are given

Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation

Directory of Open Access Journals (Sweden)

Jan Svoboda

2017-11-01

Full Text Available Muscarinic acetylcholine receptors (mAChRs have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a vast majority of place navigation tasks. However, many of these results may be potentially confounded by disruptions of functions other than spatial learning and memory. Although studies with selective antimuscarinics point to mutually opposite effects of M1 and M2 receptors, their particular contribution to spatial cognition is still poorly understood, partly due to a lack of truly selective agents. Furthermore, constitutive knock-outs do not always support results from selective antagonists. For modeling impaired spatial cognition, the scopolamine-induced amnesia model still maintains some limited validity, but there is an apparent need for more targeted approaches such as local intracerebral administration of antagonists, as well as novel techniques such as optogenetics focused on cholinergic neurons and chemogenetics aimed at cells expressing metabotropic mAChRs.

Broadband metasurface holograms: toward complete phase and amplitude engineering.

Science.gov (United States)

Wang, Qiu; Zhang, Xueqian; Xu, Yuehong; Gu, Jianqiang; Li, Yanfeng; Tian, Zhen; Singh, Ranjan; Zhang, Shuang; Han, Jiaguang; Zhang, Weili

2016-09-12

As a revolutionary three-dimensional imaging technique, holography has attracted wide attention for its ability to photographically record a light field. However, traditional phase-only or amplitude-only modulation holograms have limited image quality and resolution to reappear both amplitude and phase information required of the objects. Recent advances in metasurfaces have shown tremendous opportunities for using a planar design of artificial meta-atoms to shape the wave front of light by optimal control of both its phase and amplitude. Inspired by the concept of designer metasurfaces, we demonstrate a novel amplitude-phase modulation hologram with simultaneous five-level amplitude modulation and eight-level phase modulation. Such a design approach seeks to turn the perceived disadvantages of the traditional phase or amplitude holograms, and thus enable enhanced performance in resolution, homogeneity of amplitude distribution, precision, and signal-to-noise ratio. In particular, the unique holographic approach exhibits broadband characteristics. The method introduced here delivers more degrees of freedom, and allows for encoding highly complex information into designer metasurfaces, thus having the potential to drive next-generation technological breakthroughs in holography.

Phase-space spinor amplitudes for spin-1/2 systems

International Nuclear Information System (INIS)

Watson, P.; Bracken, A. J.

2011-01-01

The concept of phase-space amplitudes for systems with continuous degrees of freedom is generalized to finite-dimensional spin systems. Complex amplitudes are obtained on both a sphere and a finite lattice, in each case enabling a more fundamental description of pure spin states than that previously given by Wigner functions. In each case the Wigner function can be expressed as the star product of the amplitude and its conjugate, so providing a generalized Born interpretation of amplitudes that emphasizes their more fundamental status. The ordinary product of the amplitude and its conjugate produces a (generalized) spin Husimi function. The case of spin-(1/2) is treated in detail, and it is shown that phase-space amplitudes on the sphere transform correctly as spinors under rotations, despite their expression in terms of spherical harmonics. Spin amplitudes on a lattice are also found to transform as spinors. Applications are given to the phase space description of state superposition, and to the evolution in phase space of the state of a spin-(1/2) magnetic dipole in a time-dependent magnetic field.

Automation of loop amplitudes in numerical approach

International Nuclear Information System (INIS)

Fujimoto, J.; Ishikawa, T.; Shimizu, Y.; Kato, K.; Nakazawa, N.; Kaneko, T.

1997-01-01

An automatic calculating system GRACE-L1 of one-loop Feynman amplitude is reviewed. This system can be applied to 2 to 2-body one-loop processes. A sample calculation of 2 to 3-body one-loop amplitudes is also presented. (orig.)

Singularities in four-body final-state amplitudes

International Nuclear Information System (INIS)

Adhikari, S.K.

1978-01-01

Like three-body amplitudes, four-body amplitudes have subenergy threshold singularities over and above total-energy singularities. In the four-body problem we encounter a new type of subenergy singularity besides the usual two- and three-body subenergy threshold singularities. This singularity will be referred to as ''independent-pair threshold singularity'' and involves pair-subenergy threshold singularities in each of the two independent pair subenergies in four-body final states. We also study the particularly interesting case of resonant two- and three-body interactions in the four-body isobar model and the rapid (singular) dependence of the isobar amplitudes they generate in the four-body phase space. All these singularities are analyzed in the multiple-scattering formalism and it is shown that they arise from the ''next-to-last'' rescattering and hence may be represented correctly by an approximate amplitude which has that rescattering

Amplitude correlations for inelastic proton scattering from 48Ti

International Nuclear Information System (INIS)

Chou, B.H.; Mitchell, G.E.; Bilpuch, E.G.; Westerfeldt, C.R.

1981-01-01

The magnitudes and relative signs of inelastic proton channel amplitudes were determined for three decay channels for 45 5/2 + resonances in 49 V. The reduced widths in each channel follow a Porter-Thomas distribution, but extremely large amplitude correlations are observed - for one pair of channel amplitudes the relative sign is positive for 43 of 45 resonances. These results provide the first direct test of the Krieger-Porter reduced width amplitude distribution. (orig.)

Large amplitude ion-acoustic solitons in dusty plasmas

International Nuclear Information System (INIS)

Tiwari, R. S.; Jain, S. L.; Mishra, M. K.

2011-01-01

Characteristics of ion-acoustic soliton in dusty plasma, including the dynamics of heavily charged massive dust grains, are investigated following the Sagdeev Potential formalism. Retaining fourth order nonlinearities of electric potential in the expansion of the Sagdeev Potential in the energy equation for a pseudo particle and integrating the resulting energy equation, large amplitude soliton solution is determined. Variation of amplitude (A), half width (W) at half maxima and the product P = AW 2 of the Korteweg-deVries (KdV), dressed and large amplitude soliton as a function of wide range of dust concentration are numerically studied for recently observed parameters of dusty plasmas. We have also presented the region of existence of large amplitude ion-acoustic soliton in the dusty plasma by analyzing the structure of the pseudo potential. It is found that in the presence of positively charged dust grains, system supports only compressive solitons, on the other hand, in the presence of negatively charged dust grains, the system supports compressive solitons up to certain critical concentration of dust grains and above this critical concentration, the system can support rarefactive solitons also. The effects of dust concentration, charge, and mass of the dust grains, on the characteristics of KdV, dressed and large amplitude the soliton, i.e., amplitude (A), half width at half maxima (W), and product of amplitude (A) and half width at half maxima (P = AW 2 ), are discussed in detail

Renormalization Scale-Fixing for Complex Scattering Amplitudes

Energy Technology Data Exchange (ETDEWEB)

Brodsky, Stanley J.; /SLAC; Llanes-Estrada, Felipe J.; /Madrid U.

2005-12-21

We show how to fix the renormalization scale for hard-scattering exclusive processes such as deeply virtual meson electroproduction by applying the BLM prescription to the imaginary part of the scattering amplitude and employing a fixed-t dispersion relation to obtain the scale-fixed real part. In this way we resolve the ambiguity in BLM renormalization scale-setting for complex scattering amplitudes. We illustrate this by computing the H generalized parton distribution at leading twist in an analytic quark-diquark model for the parton-proton scattering amplitude which can incorporate Regge exchange contributions characteristic of the deep inelastic structure functions.

Investigating the amplitude of interactive footstep sounds and soundscape reproduction

DEFF Research Database (Denmark)

Turchet, Luca; Serafin, Stefania

2013-01-01

In this paper, we study the perception of amplitude of soundscapes and interactively generated footstep sounds provided both through headphones and a surround sound system. In particular, we investigate whether there exists a value for the amplitude of soundscapes and footstep sounds which...... of soundscapes does not significantly affect the selected amplitude of footstep sounds. Similarly, the perception of the soundscapes amplitude is not significantly affected by the selected amplitude of footstep sounds....

High Frequency Amplitude Detector for GMI Magnetic Sensors

Directory of Open Access Journals (Sweden)

Aktham Asfour

2014-12-01

Full Text Available A new concept of a high-frequency amplitude detector and demodulator for Giant-Magneto-Impedance (GMI sensors is presented. This concept combines a half wave rectifier, with outstanding capabilities and high speed, and a feedback approach that ensures the amplitude detection with easily adjustable gain. The developed detector is capable of measuring high-frequency and very low amplitude signals without the use of diode-based active rectifiers or analog multipliers. The performances of this detector are addressed throughout the paper. The full circuitry of the design is given, together with a comprehensive theoretical study of the concept and experimental validation. The detector has been used for the amplitude measurement of both single frequency and pulsed signals and for the demodulation of amplitude-modulated signals. It has also been successfully integrated in a GMI sensor prototype. Magnetic field and electrical current measurements in open- and closed-loop of this sensor have also been conducted.

Reconstruction of far-field tsunami amplitude distributions from earthquake sources

Science.gov (United States)

Geist, Eric L.; Parsons, Thomas E.

2016-01-01

The probability distribution of far-field tsunami amplitudes is explained in relation to the distribution of seismic moment at subduction zones. Tsunami amplitude distributions at tide gauge stations follow a similar functional form, well described by a tapered Pareto distribution that is parameterized by a power-law exponent and a corner amplitude. Distribution parameters are first established for eight tide gauge stations in the Pacific, using maximum likelihood estimation. A procedure is then developed to reconstruct the tsunami amplitude distribution that consists of four steps: (1) define the distribution of seismic moment at subduction zones; (2) establish a source-station scaling relation from regression analysis; (3) transform the seismic moment distribution to a tsunami amplitude distribution for each subduction zone; and (4) mix the transformed distribution for all subduction zones to an aggregate tsunami amplitude distribution specific to the tide gauge station. The tsunami amplitude distribution is adequately reconstructed for four tide gauge stations using globally constant seismic moment distribution parameters established in previous studies. In comparisons to empirical tsunami amplitude distributions from maximum likelihood estimation, the reconstructed distributions consistently exhibit higher corner amplitude values, implying that in most cases, the empirical catalogs are too short to include the largest amplitudes. Because the reconstructed distribution is based on a catalog of earthquakes that is much larger than the tsunami catalog, it is less susceptible to the effects of record-breaking events and more indicative of the actual distribution of tsunami amplitudes.

Efficient analytic computation of higher-order QCD amplitudes

International Nuclear Information System (INIS)

Bern, Z.; Chalmers, G.; Dunbar, D.C.; Kosower, D.A.

1995-01-01

The authors review techniques simplifying the analytic calculation of one-loop QCD amplitudes with many external legs, for use in next-to-leading-order corrections to multi-jet processes. Particularly useful are the constraints imposed by perturbative unitarity, collinear singularities and a supersymmetry-inspired organization of helicity amplitudes. Certain sequences of one-loop helicity amplitudes with an arbitrary number of external gluons have been obtained using these constraints

Examining the time dependence of DAMA's modulation amplitude

Science.gov (United States)

Kelso, Chris; Savage, Christopher; Sandick, Pearl; Freese, Katherine; Gondolo, Paolo

2018-03-01

If dark matter is composed of weakly interacting particles, Earth's orbital motion may induce a small annual variation in the rate at which these particles interact in a terrestrial detector. The DAMA collaboration has identified at a 9.3σ confidence level such an annual modulation in their event rate over two detector iterations, DAMA/NaI and DAMA/LIBRA, each with ˜ 7 years of observations. This data is well fit by a constant modulation amplitude for the two iterations of the experiment. We statistically examine the time dependence of the modulation amplitudes, which "by eye" appear to be decreasing with time in certain energy ranges. We perform a chi-squared goodness of fit test of the average modulation amplitudes measured by the two detector iterations which rejects the hypothesis of a consistent modulation amplitude at greater than 80, 96, and 99.6% for the 2-4, 2-5 and 2-6 keVee energy ranges, respectively. We also find that among the 14 annual cycles there are three ≳ 3σ departures from the average in our estimated data in the 5-6 keVee energy range. In addition, we examined several phenomenological models for the time dependence of the modulation amplitude. Using a maximum likelihood test, we find that descriptions of the modulation amplitude as decreasing with time are preferred over a constant modulation amplitude at anywhere between 1σ and 3σ , depending on the phenomenological model for the time dependence and the signal energy range considered. A time dependent modulation amplitude is not expected for a dark matter signal, at least for dark matter halo morphologies consistent with the DAMA signal. New data from DAMA/LIBRA-phase2 will certainly aid in determining whether any apparent time dependence is a real effect or a statistical fluctuation.

Transversity Amplitudes in Hypercharge Exchange Processes; Amplitudes de transversidad en procesos de intercambio de hipercarga

Energy Technology Data Exchange (ETDEWEB)

Aguilar Benitez de Lugo, M.

1979-07-01

In this work we present several techniques developed for the extraction of the. Transversity amplitudes governing quasi two-body meson baryon reactions with hypercharge exchange. We review the methods used In processes having a pure spin configuration, as well as the more relevant results obtained with data from K{sup p} and Tp interactions at intermediate energies. The predictions of the additive quark model and the ones following from exchange degeneracy and etoxicity are discussed. We present a formalism for amplitude analysis developed for reactions with mixed spin configurations and discuss the methods of parametric estimation of the moduli and phases of.the amplitudes, as well as the various tests employed to check the goodness of the fits. The calculation of the generalized joint density matrices is given and we propose a method based on the generalization of the idea of multipole moments, which allows to investigate the structure of the decay angular correlations and establishes the quality of the fits and the validity of the simplifying assumptions currently used in this type of studies. (Author) 43 refs.

On the singularities of massive superstring amplitudes

NARCIS (Netherlands)

Foda, O.

1987-01-01

Superstring one-loop amplitudes with massive external states are shown to be in general ill-defined due to internal on-shell propagators. However, we argue that since any massive string state (in the uncompactified theory) has a finite lifetime to decay into massless particles, such amplitudes are

Connected formulas for amplitudes in standard model

Energy Technology Data Exchange (ETDEWEB)

He, Song [CAS Key Laboratory of Theoretical Physics,Institute of Theoretical Physics, Chinese Academy of Sciences,Beijing 100190 (China); School of Physical Sciences, University of Chinese Academy of Sciences,No. 19A Yuquan Road, Beijing 100049 (China); Zhang, Yong [Department of Physics, Beijing Normal University,Beijing 100875 (China); CAS Key Laboratory of Theoretical Physics,Institute of Theoretical Physics, Chinese Academy of Sciences,Beijing 100190 (China)

2017-03-17

Witten’s twistor string theory has led to new representations of S-matrix in massless QFT as a single object, including Cachazo-He-Yuan formulas in general and connected formulas in four dimensions. As a first step towards more realistic processes of the standard model, we extend the construction to QCD tree amplitudes with massless quarks and those with a Higgs boson. For both cases, we find connected formulas in four dimensions for all multiplicities which are very similar to the one for Yang-Mills amplitudes. The formula for quark-gluon color-ordered amplitudes differs from the pure-gluon case only by a Jacobian factor that depends on flavors and orderings of the quarks. In the formula for Higgs plus multi-parton amplitudes, the massive Higgs boson is effectively described by two additional massless legs which do not appear in the Parke-Taylor factor. The latter also represents the first twistor-string/connected formula for form factors.

Source-Space Cross-Frequency Amplitude-Amplitude Coupling in Tinnitus

Directory of Open Access Journals (Sweden)

Oliver Zobay

2015-01-01

Full Text Available The thalamocortical dysrhythmia (TCD model has been influential in the development of theoretical explanations for the neurological mechanisms of tinnitus. It asserts that thalamocortical oscillations lock a region in the auditory cortex into an ectopic slow-wave theta rhythm (4–8 Hz. The cortical area surrounding this region is hypothesized to generate abnormal gamma (>30 Hz oscillations (“edge effect” giving rise to the tinnitus percept. Consequently, the model predicts enhanced cross-frequency coherence in a broad range between theta and gamma. In this magnetoencephalography study involving tinnitus and control cohorts, we investigated this prediction. Using beamforming, cross-frequency amplitude-amplitude coupling (AAC was computed within the auditory cortices for frequencies (f1,f2 between 2 and 80 Hz. We find the AAC signal to decompose into two distinct components at low (f1,f230 Hz frequencies, respectively. Studying the correlation of AAC with several key covariates (age, hearing level (HL, tinnitus handicap and duration, and HL at tinnitus frequency, we observe a statistically significant association between age and low-frequency AAC. Contrary to the TCD predictions, however, we do not find any indication of statistical differences in AAC between tinnitus and controls and thus no evidence for the predicted enhancement of cross-frequency coupling in tinnitus.

A comparison of β-adrenoceptors and muscarinic cholinergic receptors in tissues of brown bullhead catfish (Ameiurus nebulosus) from the black river and old woman creek, Ohio

Science.gov (United States)

Steevens, Jeffery A.; Baumann, Paul C.; Jones, Susan B.

1996-01-01

β-Adrenoceptors (βARs) and muscarinic cholinergic receptors were measured in brain, gill, and heart tissues of brown bullhead catfish exposed to polycyclic aromatic hydrocarbons in the Black River, Ohio, USA, and were compared to values from Old Woman Creek, Ohio, a reference site. A decreased number of βARs were found in the gill from Black River fish, possibly indicating a compensatory response subsequent to chemical stress.

Numerical evaluation of one-loop QCD amplitudes

DEFF Research Database (Denmark)

Badger, Simon David; Biedermann, Benedikt; Uwer, Peter

2012-01-01

We present the publicly available program NGluon allowing the numerical evaluation of primitive amplitudes at one-loop order in massless QCD. The program allows the computation of one-loop amplitudes for an arbitrary number of gluons. The focus of the present article is the extension to one-loop ...

Functional cortical changes in relapsing-remitting multiple sclerosis at amplitude configuration: a resting-state fMRI study

Directory of Open Access Journals (Sweden)

Liu H

2016-11-01

Full Text Available Heng Liu,1,* Hua Chen,1,* Bo Wu,1 Tijiang Zhang,1 Jinhui Wang,2,3 Kexin Huang,1 Ganjun Song,1 Jian Zhan4 1Department of Radiology, Affiliated Hospital of Zunyi Medical University, Medical Imaging Center of Guizhou Province, Zunyi, Guizhou, 2Department of Psychology, Hangzhou Normal University, 3Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, 4Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to explore the amplitude of spontaneous brain activity fluctuations in patients with relapsing–remitting multiple sclerosis (RRMS using the amplitude of low-frequency fluctuation (ALFF method. Methods: ALFF and SPM8 were utilized to assess alterations in regional spontaneous brain activities in patients with RRMS in comparison with healthy controls (HCs. The beta values of altered brain regions between patients with RRMS and HCs were extracted, and a receiver operating characteristic (ROC curve was generated to calculate the sensitivities and specificities of these different brain areas for distinguishing patients with RRMS from HCs. Pearson correlation analyses were applied to assess the relationships between the beta values of altered brain regions and disease duration and Expanded Disability Status Scale (EDSS score. Patients and participants: A total of 18 patients with RRMS (13 females; five males and 18 sex-, age-, and education-matched HCs (14 females; four males were recruited for this study. Measurements and results: Compared with HCs, patients with RRMS showed higher ALFF responses in the right fusiform gyrus (Brodmann area [BA] 37 and lower ALFF responses in the bilateral anterior cingulate cortices (BA 24 and 32, bilateral heads of the caudate nuclei, and bilateral brainstem. The ROC analysis revealed that the beta values of these abnormal brain areas

Immunocytochemical localization of choline acetyltransferase and muscarinic ACh receptors in the antenna during development of the sphinx moth Manduca sexta.

Science.gov (United States)

Clark, Julie; Meisner, Shannon; Torkkeli, Päivi H

2005-04-01

Immunocytochemistry with monoclonal antibodies was used to investigate the locations of muscarinic acetylcholine receptors (mAChR) and choline acetyltransferase (ChAT) in sections of the developing antennae of the moth Manduca sexta. The results were correlated with a previous morphological investigation in the developing antennae which allowed us to locate different cell types at various stages of development. Our findings indicated that the muscarinic cholinergic system was not restricted to the sensory neurons but was also present in glial and epidermal cells. By day 4-5 of adult development, immunoreactivity against both antibodies was present in the axons of the antennal nerve, and more intense labeling was present in sections from older pupae. At days 4-9, the cell bodies of the sensory neurons in the basal part of the epidermis were also intensely immunolabeled by the anti-mAChR antibody. In mature flagella, large numbers of cells, some with processes into hairs, were strongly labeled by both antibodies. Antennal glial cells were intensely immunolabeled with both antibodies by days 4-5, but in later stages, it was not possible to discriminate between glial and neural staining. At days 4-9, we observed a distinctly labeled layer of epidermal cells close to the developing cuticle. The expression of both ChAT and mAChRs by neurons in moth antennae may allow the regulation of excitability by endogenous ACh. Cholinergic communication between neurons and glia may be part of the system that guides axon elongation during development. The cholinergic system in the apical part of the developing epidermis could be involved in cuticle formation.

Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model.

Science.gov (United States)

Lahmy, Valentine; Long, Romain; Morin, Didier; Villard, Vanessa; Maurice, Tangui

2014-01-01

Alzheimer's disease (AD), the most prevalent dementia in the elderly, is characterized by progressive synaptic and neuronal loss. Mitochondrial dysfunctions have been consistently reported as an early event in AD and appear before Aβ deposition and memory decline. In order to define a new neuroprotectant strategy in AD targeting mitochondrial alterations, we develop tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine (ANAVEX2-73, AE37), a mixed muscarinic receptor ligand and a sigma-1 receptor (σ1R) agonist. We previously reported that ANAVEX2-73 shows anti-amnesic and neuroprotective activities in mice injected intracerebroventricular (ICV) with oligomeric amyloid-β25-35 peptide (Aβ25-35). The σ1R is present at mitochondria-associated endoplasmic reticulum (ER) membranes, where it acts as a sensor/modulator of ER stress responses and local Ca(2+) exchanges with the mitochondria. We therefore evaluated the effect of ANAVEX2-73 and PRE-084, a reference σ1R agonist, on preservation of mitochondrial integrity in Aβ25-35-injected mice. In isolated mitochondria from hippocampus preparations of Aβ25-35 injected animals, we measured respiration rates, complex activities, lipid peroxidation, Bax/Bcl-2 ratios and cytochrome c release into the cytosol. Five days after Aβ25-35 injection, mitochondrial respiration in mouse hippocampus was altered. ANAVEX2-73 (0.01-1 mg/kg IP) restored normal respiration and PRE-084 (0.5-1 mg/kg IP) increased respiration rates. Both compounds prevented Aβ25-35-induced increases in lipid peroxidation levels, Bax/Bcl-2 ratio and cytochrome c release into the cytosol, all indicators of increased toxicity. ANAVEX2-73 and PRE-084 efficiently prevented the mitochondrial respiratory dysfunction and resulting oxidative stress and apoptosis. The σ1R, targeted selectively or non-selectively, therefore appears as a valuable target for protection against mitochondrial damages in AD.

Phase and amplitude control system for Stanford Linear Accelerator

International Nuclear Information System (INIS)

Yoo, S.J.

1983-01-01

The computer controlled phase and amplitude detection system measures the instantaneous phase and amplitude of a 1 micro-second 2856 MHz rf pulse at a 180 Hz rate. This will be used for phase feedback control, and also for phase and amplitude jitter measurement. The program, which was originally written by John Fox and Keith Jobe, has been modified to improve the function of the system. The software algorithms used in the measurement are described, as is the performance of the prototype phase and amplitude detector system

Analytical structure of the 3. -->. 3 forward scattering amplitude

Energy Technology Data Exchange (ETDEWEB)

Logunov, A A; Medvedev, B V; Muzafarov, L M; Pavlov, V P; Polivanov, M K; Sukhanov, A D [AN SSSR, Moscow. Matematicheskij Inst.

1979-08-01

Analytical properties of the amplitude of 3..-->..3 forward scattering established in the framework of the Bogolyubov axiomatic approach are described. The amplitudes of the different channels of the process are boundary values of a unique analytical function of invariant variables. Crossing-symmetry property of the amplitude is proved. Analysis of the absorptive part of the amplitude is performed and the generalized optical theorem is proved which connects one of the contributions into the absorptive part with the distribution function of the inclusive process.

Relativistic amplitudes in terms of wave functions

International Nuclear Information System (INIS)

Karmanov, V.A.

1978-01-01

In the framework of the invariant diagram technique which arises at the formulation of the fueld theory on the light front the question about conditions at which the relativistic amplitudes may be expressed through the wave functions is investigated. The amplitudes obtained depend on four-vector ω, determining the light front surface. The way is shown to find such values of the four-vector ω, at which the contribution of diagrams not expressed through wave functions is minimal. The investigation carried out is equivalent to the study of the dependence of amplitudes of the old-fashioned perturbation theory in the in the infinite momentum frame on direction of the infinite momentum

Full amplitude models of 15 day Cepheids

International Nuclear Information System (INIS)

Cogan, B.C.; Cox, A.N.; King, D.S.

1980-01-01

Numerical models of Cepheids have been computed with a range of effective temperatures and compositions. The amplitudes increase if the helium abundance increases or if the effective temperature decreases. The latter effect is contrary to observational data. The models also exhibit velocity amplitudes which are much lower than those observed

Finite Amplitude Ocean Waves

Indian Academy of Sciences (India)

IAS Admin

wavelength, they are called shallow water waves. In the ... Deep and intermediate water waves are dispersive as the velocity of these depends on wavelength. This is not the ..... generation processes, the finite amplitude wave theories are very ...

Light Meson Distribution Amplitudes

CERN Document Server

Arthur, R.; Brommel, D.; Donnellan, M.A.; Flynn, J.M.; Juttner, A.; de Lima, H.Pedroso; Rae, T.D.; Sachrajda, C.T.; Samways, B.

2010-01-01

We calculated the first two moments of the light-cone distribution amplitudes for the pseudoscalar mesons ($\\pi$ and $K$) and the longitudinally polarised vector mesons ($\\rho$, $K^*$ and $\\phi$) as part of the UKQCD and RBC collaborations' $N_f=2+1$ domain-wall fermion phenomenology programme. These quantities were obtained with a good precision and, in particular, the expected effects of $SU(3)$-flavour symmetry breaking were observed. Operators were renormalised non-perturbatively and extrapolations to the physical point were made, guided by leading order chiral perturbation theory. The main results presented are for two volumes, $16^3\\times 32$ and $24^3\\times 64$, with a common lattice spacing. Preliminary results for a lattice with a finer lattice spacing, $32^3\\times64$, are discussed and a first look is taken at the use of twisted boundary conditions to extract distribution amplitudes.

Automated force controller for amplitude modulation atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Miyagi, Atsushi, E-mail: atsushi.miyagi@inserm.fr, E-mail: simon.scheuring@inserm.fr; Scheuring, Simon, E-mail: atsushi.miyagi@inserm.fr, E-mail: simon.scheuring@inserm.fr [U1006 INSERM, Université Aix-Marseille, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, 13009 Marseille (France)

2016-05-15

Atomic Force Microscopy (AFM) is widely used in physics, chemistry, and biology to analyze the topography of a sample at nanometer resolution. Controlling precisely the force applied by the AFM tip to the sample is a prerequisite for faithful and reproducible imaging. In amplitude modulation (oscillating) mode AFM, the applied force depends on the free and the setpoint amplitudes of the cantilever oscillation. Therefore, for keeping the applied force constant, not only the setpoint amplitude but also the free amplitude must be kept constant. While the AFM user defines the setpoint amplitude, the free amplitude is typically subject to uncontrollable drift, and hence, unfortunately, the real applied force is permanently drifting during an experiment. This is particularly harmful in biological sciences where increased force destroys the soft biological matter. Here, we have developed a strategy and an electronic circuit that analyzes permanently the free amplitude of oscillation and readjusts the excitation to maintain the free amplitude constant. As a consequence, the real applied force is permanently and automatically controlled with picoNewton precision. With this circuit associated to a high-speed AFM, we illustrate the power of the development through imaging over long-duration and at various forces. The development is applicable for all AFMs and will widen the applicability of AFM to a larger range of samples and to a larger range of (non-specialist) users. Furthermore, from controlled force imaging experiments, the interaction strength between biomolecules can be analyzed.

Calculation and modular properties of multiloop superstring amplitudes

International Nuclear Information System (INIS)

Danilov, G. S.

2013-01-01

Multiloop superstring amplitudes are calculated within an extensively used gauge where the two-dimensional gravitino field carries Grassmann moduli. In general, the amplitudes possess, instead of modular symmetry, symmetry with respect to modular transformation supplemented with appropriate transformations of two-dimensional local supersymmetry. If the number of loops is larger than three, the integrationmeasures are notmodular forms, while the expression for the amplitude contains integrals along the boundary of the fundamental region of the modular group.

Interactions between allosteric modulators and 4-DAMP and other antagonists at muscarinic receptors: potential significance of the distance between the N and Carboxyl C atoms in the molecules of antagonists

Czech Academy of Sciences Publication Activity Database

Lysíková, Michaela; Havlas, Zdeněk; Tuček, Stanislav

2001-01-01

Roč. 26, č. 4 (2001), s. 383-394 ISSN 0364-3190 R&D Projects: GA ČR GA309/99/0214; GA MŠk LN00A032 Institutional research plan: CEZ:AV0Z5011922 Keywords : muscarinic receptors * allosteric modulation * 4-DAMP Subject RIV: ED - Physiology Impact factor: 1.638, year: 2001

Effects of amplitude modulation on perception of wind turbine noise

Energy Technology Data Exchange (ETDEWEB)

Yoon, Ki Seop; Lee, Soo Gab; Gwak, Doo Young [Dept. of Mechanical and Aerospace Engineering, Seoul National University, Seoul (Korea, Republic of); Seong, Yeol Wan [Ammunition Engineering Team, Defense Agency for Technology and Quality, Daejeon (Korea, Republic of); Lee, Seung Hoon [Aerodynamics Research Team, Korea Aerospace Research Institute, Daejeon (Korea, Republic of); Hong, Ji Young [Transportation Environmental Research Team, Green Transport and Logistics Institute, Korea Railroad Research Institute, Uiwang (Korea, Republic of)

2016-10-15

Wind turbine noise is considered to be easily detectable and highly annoying at relatively lower sound levels than other noise sources. Many previous studies attributed this characteristic to amplitude modulation. However, it is unclear whether amplitude modulation is the main cause of these properties of wind turbine noise. Therefore, the aim of the current study is to identify the relationship between amplitude modulation and these two properties of wind turbine noise. For this investigation, two experiments were conducted. In the first experiment, 12 participants determined the detection thresholds of six target sounds in the presence of background noise. In the second experiment, 12 participants matched the loudness of modified sounds without amplitude modulation to that of target sounds with amplitude modulation. The results showed that the detection threshold was lowered as the modulation depth increased; additionally, sounds with amplitude modulation had higher subjective loudness than those without amplitude modulation.

Effects of amplitude modulation on perception of wind turbine noise

International Nuclear Information System (INIS)

Yoon, Ki Seop; Lee, Soo Gab; Gwak, Doo Young; Seong, Yeol Wan; Lee, Seung Hoon; Hong, Ji Young

2016-01-01

Wind turbine noise is considered to be easily detectable and highly annoying at relatively lower sound levels than other noise sources. Many previous studies attributed this characteristic to amplitude modulation. However, it is unclear whether amplitude modulation is the main cause of these properties of wind turbine noise. Therefore, the aim of the current study is to identify the relationship between amplitude modulation and these two properties of wind turbine noise. For this investigation, two experiments were conducted. In the first experiment, 12 participants determined the detection thresholds of six target sounds in the presence of background noise. In the second experiment, 12 participants matched the loudness of modified sounds without amplitude modulation to that of target sounds with amplitude modulation. The results showed that the detection threshold was lowered as the modulation depth increased; additionally, sounds with amplitude modulation had higher subjective loudness than those without amplitude modulation

Conformal amplitude hierarchy and the Poincaré disk

Science.gov (United States)

Shimada, Hirohiko

2018-02-01

The amplitude for the singlet channels in the 4-point function of the fundamental field in the conformal field theory of the 2d O(n) model is studied as a function of n. For a generic value of n, the 4-point function has infinitely many amplitudes, whose landscape can be very spiky as the higher amplitude changes its sign many times at the simple poles, which generalize the unique pole of the energy operator amplitude at n = 0. In the stadard parameterization of n by angle in unit of π, we find that the zeros and poles happen at the rational angles, forming a hierarchical tree structure inherent in the Poincaré disk. Some relation between the amplitude and the Farey path, a piecewise geodesic that visits these zeros and poles, is suggested. In this hierarchy, the symmetry of the congruence subgroup Γ(2) of SL(2, ℤ) naturally arises from the two clearly distinct even/odd classes of the rational angles, in which one respectively gets the truncated operator algebras and the logarithmic 4-point functions.

Cholinergic blockade under working memory demands encountered by increased rehearsal strategies: evidence from fMRI in healthy subjects.

Science.gov (United States)

Voss, Bianca; Thienel, Renate; Reske, Martina; Kellermann, Thilo; Sheldrick, Abigail J; Halfter, Sarah; Radenbach, Katrin; Shah, Nadim J; Habel, Ute; Kircher, Tilo T J

2012-06-01

The connection between cholinergic transmission and cognitive performance has been established in behavioural studies. The specific contribution of the muscarinic receptor system on cognitive performance and brain activation, however, has not been evaluated satisfyingly. To investigate the specific contribution of the muscarinic transmission on neural correlates of working memory, we examined the effects of scopolamine, an antagonist of the muscarinic receptors, using functional magnetic resonance imaging (fMRI). Fifteen healthy male, non-smoking subjects performed a fMRI scanning session following the application of scopolamine (0.4 mg, i.v.) or saline in a placebo-controlled, repeated measure, pseudo-randomized, single-blind design. Working memory was probed using an n-back task. Compared to placebo, challenging the cholinergic transmission with scopolamine resulted in hypoactivations in parietal, occipital and cerebellar areas and hyperactivations in frontal and prefrontal areas. These alterations are interpreted as compensatory strategies used to account for downregulation due to muscarinic acetylcholine blockade in parietal and cerebral storage systems by increased activation in frontal and prefrontal areas related to working memory rehearsal. Our results further underline the importance of cholinergic transmission to working memory performance and determine the specific contribution of muscarinic transmission on cerebral activation associated with executive functioning.

Topological amplitudes in string theory

International Nuclear Information System (INIS)

Antoniadis, I.; Taylor, T.R.

1993-07-01

We show that certain type II string amplitudes at genus g are given by the topological partition F g discussed recently by Bershadsky, Cecotti, Ooguri and Vafa. These amplitudes give rise to a term in the four-dimensional effective action of the form Σ g F g W 2g , where W is the chiral superfield of N = 2 supergravitational multiplet. The holomorphic anomaly of F g is related to non-localities of the effective action due to the propagation of massless states. This result generalizes the holomorphic anomaly of the one loop case which is known to lead to non-harmonic gravitational couplings. (author). 22 refs, 2 figs

Mapping Pn amplitude spreading and attenuation in Asia

Energy Technology Data Exchange (ETDEWEB)

Yang, Xiaoning [Los Alamos National Laboratory; Phillips, William S [Los Alamos National Laboratory; Stead, Richard J [Los Alamos National Laboratory

2010-12-06

Pn travels most of its path in the mantle lid. Mapping the lateral variation of Pn amplitude attenuation sheds light on material properties and dynamics of the uppermost region of the mantle. Pn amplitude variation depends on the wavefront geometric spreading as well as material attenuation. We investigated Pn geometric spreading, which is much more complex than a traditionally assumed power-law spreading model, using both synthetic and observed amplitude data collected in Asia. We derived a new Pn spreading model based on the formulation that was proposed previously to account for the spherical shape of the Earth (Yang et. al., BSSA, 2007). New parameters derived for the spreading model provide much better correction for Pn amplitudes in terms of residual behavior. Because we used observed Pn amplitudes to construct the model, the model incorporates not only the effect of the Earth's spherical shape, but also the effect of potential upper-mantle velocity gradients in the region. Using the new spreading model, we corrected Pn amplitudes measured at 1, 2, 4 and 6 Hz and conducted attenuation tomography. The resulting Pn attenuation model correlates well with the regional geology. We see high attenuation in regions such as northern Tibetan Plateau and the western Pacific subduction zone, and low attenuation for stable blocks such as Sichuan and Tarim basins.

Macro- and microclimate conditions may alter grapevine deacclimation: variation in thermal amplitude in two contrasting wine regions from North and South America

Science.gov (United States)

Antivilo, Francisco Gonzalez; Paz, Rosalía Cristina; Keller, Markus; Borgo, Roberto; Tognetti, Jorge; Juñent, Fidel Roig

2017-12-01

Low temperature is a limiting factor that affects vineyard distribution globally. The level of cold hardiness acquired during the dormant season by Vitis sp. is crucial for winter survival. Most research published on this topic has been generated beyond 40° N latitude, where daily mean temperatures may attain injurious levels during the dormant season resulting in significant damage to vines and buds. Symptoms of cold injury have been identified in Mendoza (32-35° S latitude), a Southern Hemisphere wine region characterized by a high thermal amplitude, and warm winds during the dormant season. These symptoms have usually been attributed to drought and/or pathogens, but not to rapid deacclimation followed by injurious low temperatures. Because local information on meteorological events as probable causes is scarce, this research was designed to test and study this assumption by comparing macro-, meso-, and microclimatic data from Mendoza, Argentina, and eastern Washington, USA. The goal was to unveil why freezing damage has occurred in both regions, despite the existence of large climatic differences. Because environmental parameters under field conditions may not correspond to data recorded by conventional weather stations, sensors were installed in vineyards for comparison. Microclimatic conditions on grapevines were also evaluated to assess the most vulnerable portions of field-grown grapevines. In order to better understand if it may be possible to modify cold hardiness status in a short period with high thermal amplitude conditions, deacclimation was induced using a thermal treatment. Hence, despite the fact that Mendoza is warmer, and temperatures are not as extreme as in Washington, high daily thermal amplitude might be partially involved in plant deacclimation, leading to a differential cold hardiness response.

Simplicity in the structure of QED and gravity amplitudes

Energy Technology Data Exchange (ETDEWEB)

Badger, Simon [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Bjerrum-Bohr, N.E.J. [Institute for Advanced Study, Princeton, NJ (United States). School of Natural Sciences; Vanhove, Pierre [Institut des Hautes Etudes Scientifiques IHES, Bures sur Yvette (France); CEA, IPhT, CNRS, URA, Gif-sur-Yvette, (France). Inst. de Physique Theorique

2008-11-15

We investigate generic properties of one-loop amplitudes in unordered gauge theories in four dimensions. For such theories the organisation of amplitudes in manifestly crossing symmetric expressions poses restrictions on their structure and results in remarkable cancellations. We show that one-loop multi-photon amplitudes in QED with at least eight external photons are given only by scalar box integral functions. This QED 'no-triangle' property is true for all helicity configurations and has similarities to the 'notriangle' property found in the case of maximal N=8 supergravity. Results are derived both via a world-line formalism as well as using on-shell unitarity methods. We show that the simple structure of the loop amplitude originates from the extremely good BCFW scaling behaviour of the QED tree-amplitude. (orig.)

Simplicity in the structure of QED and gravity amplitudes

International Nuclear Information System (INIS)

Badger, Simon; Bjerrum-Bohr, N.E.J.; Vanhove, Pierre; CEA, IPhT, CNRS, URA, Gif-sur-Yvette,

2008-11-01

We investigate generic properties of one-loop amplitudes in unordered gauge theories in four dimensions. For such theories the organisation of amplitudes in manifestly crossing symmetric expressions poses restrictions on their structure and results in remarkable cancellations. We show that one-loop multi-photon amplitudes in QED with at least eight external photons are given only by scalar box integral functions. This QED 'no-triangle' property is true for all helicity configurations and has similarities to the 'notriangle' property found in the case of maximal N=8 supergravity. Results are derived both via a world-line formalism as well as using on-shell unitarity methods. We show that the simple structure of the loop amplitude originates from the extremely good BCFW scaling behaviour of the QED tree-amplitude. (orig.)

Multi-loop string amplitudes and Riemann surfaces

International Nuclear Information System (INIS)

Taylor, J.G.

1986-01-01

The paper was presented at the workshop on 'Supersymmetry and its applications', Cambridge, United Kingdom, 1985. Super-string theory is discussed under the following topic headings: the functional approach to the string amplitude, Rieman surfaces, the determinants Δsub(epsilon)(1) and Δsub(epsilon)(2), Green's functions, total amplitude, and divergence analysis. (U.K.)

Amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in migraine patients: a resting-state functional MRI study

International Nuclear Information System (INIS)

Wang, J.-J.; Chen, X.; Sah, S.K.; Zeng, C.; Li, Y.-M.; Li, N.; Liu, M.-Q.; Du, S.-I.

2016-01-01

Aim: To evaluate the amplitude of low-frequency oscillations (LFOs) of the brain in migraine patients using amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in the interictal period, in comparison to healthy controls (HCs). Materials and methods: A total of 54 subjects, including 30 migraineurs and 24 gender- and age-matched HCs completed the fMRI. All the data and ALFF, fALFF analyses were preprocessed with the Data Processing Assistant for Resting-State fMRI (DPARSF). All of the statistical analyses were performed using the REST software to explore the differences in ALFF and fALFF between migraine patients and HCs. Results: In contrast to HCs, migraine patients showed significant ALFF increase in the left medulla and pons, the bilateral cerebellum posterior lobe and right insula. The regions showing decreased ALFF in migraine patients included the bilateral cerebellum posterior lobe, left cerebellum anterior lobe, bilateral orbital cortex, right middle frontal gyrus, bilateral occipital lobe, right fusiform gyrus, and bilateral postcentral gyrus. The fALFFs in migraine patients were significantly increased in the bilateral insular and left orbital cortex, but were decreased in the left occipital lobe and bilateral cerebellum posterior lobe. Conclusion: These ALFF and fALFF alterations in the brain regions of migraineurs are in keeping with the domains associated with pain and cognition. Such brain functional alteration may contribute to further understanding of migraine-related network imbalances demonstrated in previous studies. - Highlights: • Migraine is a common, paroxysmal, highly disabling primary headache disorder. • Resting-state fMRI offers a novel approach to measure spontaneous brain activity in migraine patients • The ALFF and fALFF alterations in migraineurs' brain regions are in keeping with the domains associated with pain and cognition.

Particle Distribution Modification by Low Amplitude Modes

International Nuclear Information System (INIS)

White, R.B.; Gorelenkov, N.; Heidbrink, W.W.; Van Zeeland, M.A.

2009-01-01

Modification of a high energy particle distribution by a spectrum of low amplitude modes is investigated using a guiding center code. Only through resonance are modes effective in modifying the distribution. Diagnostics are used to illustrate the mode-particle interaction and to find which effects are relevant in producing significant resonance, including kinetic Poincare plots and plots showing those orbits with time averaged mode-particle energy transfer. Effects of pitch angle scattering and drag are studied, as well as plasma rotation and time dependence of the equilibrium and mode frequencies. A specific example of changes observed in a DIII-D deuterium beam distribution in the presence of low amplitude experimentally validated Toroidal Alfven (TAE) eigenmodes and Reversed Shear Alfven (RSAE) eigenmodes is examined in detail. Comparison with experimental data shows that multiple low amplitude modes can account for significant modification of high energy beam particle distributions. It is found that there is a stochastic threshold for beam profile modification, and that the experimental amplitudes are only slightly above this threshold.

Amplitude chimeras and chimera death in dynamical networks

International Nuclear Information System (INIS)

Zakharova, Anna; Kapeller, Marie; Schöll, Eckehard

2016-01-01

We find chimera states with respect to amplitude dynamics in a network of Stuart- Landau oscillators. These partially coherent and partially incoherent spatio-temporal patterns appear due to the interplay of nonlocal network topology and symmetry-breaking coupling. As the coupling range is increased, the oscillations are quenched, amplitude chimeras disappear and the network enters a symmetry-breaking stationary state. This particular regime is a novel pattern which we call chimera death. It is characterized by the coexistence of spatially coherent and incoherent inhomogeneous steady states and therefore combines the features of chimera state and oscillation death. Additionally, we show two different transition scenarios from amplitude chimera to chimera death. Moreover, for amplitude chimeras we uncover the mechanism of transition towards in-phase synchronized regime and discuss the role of initial conditions. (paper)

Euclidean to Minkowski Bethe-Salpeter amplitude and observables

International Nuclear Information System (INIS)

Carbonell, J.; Frederico, T.; Karmanov, V.A.

2017-01-01

We propose a method to reconstruct the Bethe-Salpeter amplitude in Minkowski space given the Euclidean Bethe-Salpeter amplitude - or alternatively the light-front wave function - as input. The method is based on the numerical inversion of the Nakanishi integral representation and computing the corresponding weight function. This inversion procedure is, in general, rather unstable, and we propose several ways to considerably reduce the instabilities. In terms of the Nakanishi weight function, one can easily compute the BS amplitude, the LF wave function and the electromagnetic form factor. The latter ones are very stable in spite of residual instabilities in the weight function. This procedure allows both, to continue the Euclidean BS solution in the Minkowski space and to obtain a BS amplitude from a LF wave function. (orig.)

Euclidean to Minkowski Bethe-Salpeter amplitude and observables

Energy Technology Data Exchange (ETDEWEB)

Carbonell, J. [Universite Paris-Sud, IN2P3-CNRS, Institut de Physique Nucleaire, Orsay Cedex (France); Frederico, T. [Instituto Tecnologico de Aeronautica, DCTA, Sao Jose dos Campos (Brazil); Karmanov, V.A. [Lebedev Physical Institute, Moscow (Russian Federation)

2017-01-15

We propose a method to reconstruct the Bethe-Salpeter amplitude in Minkowski space given the Euclidean Bethe-Salpeter amplitude - or alternatively the light-front wave function - as input. The method is based on the numerical inversion of the Nakanishi integral representation and computing the corresponding weight function. This inversion procedure is, in general, rather unstable, and we propose several ways to considerably reduce the instabilities. In terms of the Nakanishi weight function, one can easily compute the BS amplitude, the LF wave function and the electromagnetic form factor. The latter ones are very stable in spite of residual instabilities in the weight function. This procedure allows both, to continue the Euclidean BS solution in the Minkowski space and to obtain a BS amplitude from a LF wave function. (orig.)

The amplitude of quantum field theory

International Nuclear Information System (INIS)

Medvedev, B.V.; Pavlov, V.P.; Polivanov, M.K.; Sukhanov, A.D.

1989-01-01

General properties of the transition amplitude in axiomatic quantum field theory are discussed. Bogolyubov's axiomatic method is chosen as the variant of the theory. The axioms of this method are analyzed. In particular, the significance of the off-shell extension and of the various forms of the causality condition are examined. A complete proof is given of the existence of a single analytic function whose boundary values are the amplitudes of all channels of a process with given particle number

Amplitude and Ascoli analysis

International Nuclear Information System (INIS)

Hansen, J.D.

1976-01-01

This article discusses the partial wave analysis of two, three and four meson systems. The difference between the two approaches, referred to as amplitude and Ascoli analysis is discussed. Some of the results obtained with these methods are shown. (B.R.H.)

Algebraic evaluation of rational polynomials in one-loop amplitudes

International Nuclear Information System (INIS)

Binoth, Thomas; Guillet, Jean-Philippe; Heinrich, Gudrun

2007-01-01

One-loop amplitudes are to a large extent determined by their unitarity cuts in four dimensions. We show that the remaining rational terms can be obtained from the ultraviolet behaviour of the amplitude, and determine universal form factors for these rational parts by applying reduction techniques to the Feynman diagrammatic representation of the amplitude. The method is valid for massless and massive internal particles. We illustrate this method by evaluating the rational terms of the one-loop amplitudes for gg→H, γγ→γγ, gg→gg,γγ→ggg and γγ→γγγγ

Proof of the fundamental BCJ relations for QCD amplitudes

International Nuclear Information System (INIS)

Cruz, Leonardo de la; Kniss, Alexander; Weinzierl, Stefan

2015-01-01

The fundamental BCJ-relation is a linear relation between primitive tree amplitudes with different cyclic orderings. The cyclic orderings differ by the insertion place of one gluon. The coefficients of the fundamental BCJ-relation are linear in the Lorentz invariants 2p_ip_j. The BCJ-relations are well established for pure gluonic amplitudes as well as for amplitudes in N=4 super-Yang-Mills theory. Recently, it has been conjectured that the BCJ-relations hold also for QCD amplitudes. In this paper we give a proof of this conjecture. The proof is valid for massless and massive quarks.

Amplitude dependent damping in single crystalline high purity molybdenum

International Nuclear Information System (INIS)

Zelada-Lambri, G.I; Lambri, O.A; Garcia, J.A; Lomer, J.N

2004-01-01

Amplitude dependent damping measurements were performed on high purity single crystalline molybdenum at several different constant temperatures between room temperature and 1273K. The employed samples were single crystals with the orientation, having a residual resistivity ratio of about 8000. Previously to the amplitude dependent damping tests, the samples were subjected to different thermomechanical histories. Amplitude dependent damping effects appear only during the first heating run in temperature where the samples have the thermomechanical state of the deformation process at room temperature. In the subsequent run-ups in temperature, i.e, after subsequent annealings, amplitude dependent damping effects were not detected (au)

Analytic representations of Yang–Mills amplitudes

Energy Technology Data Exchange (ETDEWEB)

Bjerrum-Bohr, N.E.J. [Niels Bohr International Academy and Discovery Center, The Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen Ø (Denmark); Bourjaily, Jacob L., E-mail: bourjaily@nbi.ku.dk [Niels Bohr International Academy and Discovery Center, The Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen Ø (Denmark); Damgaard, Poul H. [Niels Bohr International Academy and Discovery Center, The Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen Ø (Denmark); Feng, Bo [Zhejiang Institute of Modern Physics, Zhejiang University, Hangzhou City, 310027 (China)

2016-12-15

Scattering amplitudes in Yang–Mills theory can be represented in the formalism of Cachazo, He and Yuan (CHY) as integrals over an auxiliary projective space—fully localized on the support of the scattering equations. Because solving the scattering equations is difficult and summing over the solutions algebraically complex, a method of directly integrating the terms that appear in this representation has long been sought. We solve this important open problem by first rewriting the terms in a manifestly Möbius-invariant form and then using monodromy relations (inspired by analogy to string theory) to decompose terms into those for which combinatorial rules of integration are known. The result is the foundations of a systematic procedure to obtain analytic, covariant forms of Yang–Mills tree-amplitudes for any number of external legs and in any number of dimensions. As examples, we provide compact analytic expressions for amplitudes involving up to six gluons of arbitrary helicities.

Scattering amplitudes from multivariate polynomial division

Energy Technology Data Exchange (ETDEWEB)

Mastrolia, Pierpaolo, E-mail: pierpaolo.mastrolia@cern.ch [Max-Planck-Institut fuer Physik, Foehringer Ring 6, 80805 Muenchen (Germany); Dipartimento di Fisica e Astronomia, Universita di Padova, Padova (Italy); INFN Sezione di Padova, via Marzolo 8, 35131 Padova (Italy); Mirabella, Edoardo, E-mail: mirabell@mppmu.mpg.de [Max-Planck-Institut fuer Physik, Foehringer Ring 6, 80805 Muenchen (Germany); Ossola, Giovanni, E-mail: GOssola@citytech.cuny.edu [New York City College of Technology, City University of New York, 300 Jay Street, Brooklyn, NY 11201 (United States); Graduate School and University Center, City University of New York, 365 Fifth Avenue, New York, NY 10016 (United States); Peraro, Tiziano, E-mail: peraro@mppmu.mpg.de [Max-Planck-Institut fuer Physik, Foehringer Ring 6, 80805 Muenchen (Germany)

2012-11-15

We show that the evaluation of scattering amplitudes can be formulated as a problem of multivariate polynomial division, with the components of the integration-momenta as indeterminates. We present a recurrence relation which, independently of the number of loops, leads to the multi-particle pole decomposition of the integrands of the scattering amplitudes. The recursive algorithm is based on the weak Nullstellensatz theorem and on the division modulo the Groebner basis associated to all possible multi-particle cuts. We apply it to dimensionally regulated one-loop amplitudes, recovering the well-known integrand-decomposition formula. Finally, we focus on the maximum-cut, defined as a system of on-shell conditions constraining the components of all the integration-momenta. By means of the Finiteness Theorem and of the Shape Lemma, we prove that the residue at the maximum-cut is parametrized by a number of coefficients equal to the number of solutions of the cut itself.

True amplitude wave equation migration arising from true amplitude one-way wave equations

Science.gov (United States)

Zhang, Yu; Zhang, Guanquan; Bleistein, Norman

2003-10-01

One-way wave operators are powerful tools for use in forward modelling and inversion. Their implementation, however, involves introduction of the square root of an operator as a pseudo-differential operator. Furthermore, a simple factoring of the wave operator produces one-way wave equations that yield the same travel times as the full wave equation, but do not yield accurate amplitudes except for homogeneous media and for almost all points in heterogeneous media. Here, we present augmented one-way wave equations. We show that these equations yield solutions for which the leading order asymptotic amplitude as well as the travel time satisfy the same differential equations as the corresponding functions for the full wave equation. Exact representations of the square-root operator appearing in these differential equations are elusive, except in cases in which the heterogeneity of the medium is independent of the transverse spatial variables. Here, we address the fully heterogeneous case. Singling out depth as the preferred direction of propagation, we introduce a representation of the square-root operator as an integral in which a rational function of the transverse Laplacian appears in the integrand. This allows us to carry out explicit asymptotic analysis of the resulting one-way wave equations. To do this, we introduce an auxiliary function that satisfies a lower dimensional wave equation in transverse spatial variables only. We prove that ray theory for these one-way wave equations leads to one-way eikonal equations and the correct leading order transport equation for the full wave equation. We then introduce appropriate boundary conditions at z = 0 to generate waves at depth whose quotient leads to a reflector map and an estimate of the ray theoretical reflection coefficient on the reflector. Thus, these true amplitude one-way wave equations lead to a 'true amplitude wave equation migration' (WEM) method. In fact, we prove that applying the WEM imaging condition

Effect of aqueous extract of mango kernel (Mangifera Indica on basal activity of virgin rat uterine smooth muscle: role of muscarinic receptors

Directory of Open Access Journals (Sweden)

Mehdi Noureddini

2017-04-01

Full Text Available Background: Mango belongs to the Anacardiaceae and the extracts from its stems, leaves, fruit and kernel are reported to affect smooth muscle contractility. We studied the role of cholinergic muscarinic receptors for the effects of aqueous extract of mango kernel (Mangifera indica on the basal activity of virgin rat uterine smooth muscle. Materials and Methods: In this experimental study, mid-sections (n=24 of the uterine of healthy virgin rats were placed in an organ bath containing carbonated Tyrode’s solution under 1 g tension. The cumulative effects of the aqueous extracts of mango kernel (0.002, 0.02, 0.2, 2, 20, 200, and 2000 μg/mL or extract vehicle (Tyrode’s solution in the presence or absence of atropine were examined by isometric method using the strength, frequency and contractile activity of uterine smooth muscle. Results: The cumulative concentrations (0.002-20 µg/ml of mango kernel aqueous extract was significantly decreased the strength, frequency and contractile activity of uterine smooth muscle, but the contractile activity was returned to the basal level at the concentrations of 200 and 2000 µg/ml. Atropine (1 µM could not significantly change the effects of cumulative use of extract on the strength and contractile activity of uterine smooth muscle, but it significantly enhanced the contractile frequency at low concentrations. Conclusion: The effects of aqueous extract of mango kernel on the activity of the uterine smooth muscle might not be through cholinergic muscarinic receptors and atropine could enhance the effects of the extract on frequency through other receptors.

A two-loop four-gluon helicity amplitude in QCD

Energy Technology Data Exchange (ETDEWEB)

Dixon, L.

2000-01-06

The authors present the two-loop pure gauge contribution to the gluon-gluon scattering amplitude with maximal helicity violation. The construction of the amplitude does not rely directly on Feynman diagrams, but instead uses its analytic properties 4--2{epsilon} dimensions. The authors evaluate the loop integrals appearing in the amplitude through order({epsilon}{sup 0})in terms of polylogarithms.

Improved pion pion scattering amplitude from dispersion relation formalism

International Nuclear Information System (INIS)

Cavalcante, I.P.; Coutinho, Y.A.; Borges, J. Sa

2005-01-01

Pion-pion scattering amplitude is obtained from Chiral Perturbation Theory at one- and two-loop approximations. Dispersion relation formalism provides a more economic method, which was proved to reproduce the analytical structure of that amplitude at both approximation levels. This work extends the use of the formalism in order to compute further unitarity corrections to partial waves, including the D-wave amplitude. (author)

The zerology of kaon-nucleon forward scattering amplitudes

International Nuclear Information System (INIS)

Dumbrajs, O.

1981-01-01

It has been realized for a long time that zeros of the forward kaon-nucleon scattering amplitudes are useful in correlating different low and high-energy scattering parameters and in providing a consistency test of available data. The simplest possibility of exploring zeros is to evaluate the ordinary dispersion relations in the complex energy plane. The more natural way of bringing zeros of amplitudes into play is to consider either one of the more sophisticated forms of dispersion relations: i) phase dispersion relations, ii) inverse-amplitude dispersion relations, iii) logarithmic dispersion relations, or to apply the maximum modulus theorem and a factorization theorem. The author concentrates on the use of logarithmic dispersion relations because this approach seems to be the most convenient one for future extensions to nonforward scattering data analyses based on the zeros of the amplitude. (Auth.)

Jump phenomena. [large amplitude responses of nonlinear systems

Science.gov (United States)

Reiss, E. L.

1980-01-01

The paper considers jump phenomena composed of large amplitude responses of nonlinear systems caused by small amplitude disturbances. Physical problems where large jumps in the solution amplitude are important features of the response are described, including snap buckling of elastic shells, chemical reactions leading to combustion and explosion, and long-term climatic changes of the earth's atmosphere. A new method of rational functions was then developed which consists of representing the solutions of the jump problems as rational functions of the small disturbance parameter; this method can solve jump problems explicitly.

Phase and amplitude detection system for the Stanford Linear Accelerator

International Nuclear Information System (INIS)

Fox, J.D.; Schwarz, H.D.

1983-01-01

A computer controlled phase and amplitude detection system to measure and stabilize the rf power sources in the Stanford Linear Accelerator is described. This system measures the instantaneous phase and amplitude of a 1 microsecond 2856 MHz rf pulse and will be used for phase feedback control and for amplitude and phase jitter detection. This paper discusses the measurement system performance requirements for the operation of the Stanford Linear Collider, and the design and implementation of the phase and amplitude detection system. The fundamental software algorithms used in the measurement are described, as is the performance of the prototype phase and amplitude detector system

An Analysis of Fundamental Mode Surface Wave Amplitude Measurements

Science.gov (United States)

Schardong, L.; Ferreira, A. M.; van Heijst, H. J.; Ritsema, J.

2014-12-01

Seismic tomography is a powerful tool to decipher the Earth's interior structure at various scales. Traveltimes of seismic waves are widely used to build velocity models, whereas amplitudes are still only seldomly accounted for. This mainly results from our limited ability to separate the various physical effects responsible for observed amplitude variations, such as focussing/defocussing, scattering and source effects. We present new measurements from 50 global earthquakes of fundamental-mode Rayleigh and Love wave amplitude anomalies measured in the period range 35-275 seconds using two different schemes: (i) a standard time-domain amplitude power ratio technique; and (ii) a mode-branch stripping scheme. For minor-arc data, we observe amplitude anomalies with respect to PREM in the range of 0-4, for which the two measurement techniques show a very good overall agreement. We present here a statistical analysis and comparison of these datasets, as well as comparisons with theoretical calculations for a variety of 3-D Earth models. We assess the geographical coherency of the measurements, and investigate the impact of source, path and receiver effects on surface wave amplitudes, as well as their variations with frequency in a wider range than previously studied.

Light Diffraction by Large Amplitude Ultrasonic Waves in Liquids

Science.gov (United States)

Adler, Laszlo; Cantrell, John H.; Yost, William T.

2016-01-01

Light diffraction from ultrasound, which can be used to investigate nonlinear acoustic phenomena in liquids, is reported for wave amplitudes larger than that typically reported in the literature. Large amplitude waves result in waveform distortion due to the nonlinearity of the medium that generates harmonics and produces asymmetries in the light diffraction pattern. For standing waves with amplitudes above a threshold value, subharmonics are generated in addition to the harmonics and produce additional diffraction orders of the incident light. With increasing drive amplitude above the threshold a cascade of period-doubling subharmonics are generated, terminating in a region characterized by a random, incoherent (chaotic) diffraction pattern. To explain the experimental results a toy model is introduced, which is derived from traveling wave solutions of the nonlinear wave equation corresponding to the fundamental and second harmonic standing waves. The toy model reduces the nonlinear partial differential equation to a mathematically more tractable nonlinear ordinary differential equation. The model predicts the experimentally observed cascade of period-doubling subharmonics terminating in chaos that occurs with increasing drive amplitudes above the threshold value. The calculated threshold amplitude is consistent with the value estimated from the experimental data.

A proposed physical analog for a quantum probability amplitude

Science.gov (United States)

Boyd, Jeffrey

What is the physical analog of a probability amplitude? All quantum mathematics, including quantum information, is built on amplitudes. Every other science uses probabilities; QM alone uses their square root. Why? This question has been asked for a century, but no one previously has proposed an answer. We will present cylindrical helices moving toward a particle source, which particles follow backwards. Consider Feynman's book QED. He speaks of amplitudes moving through space like the hand of a spinning clock. His hand is a complex vector. It traces a cylindrical helix in Cartesian space. The Theory of Elementary Waves changes direction so Feynman's clock faces move toward the particle source. Particles follow amplitudes (quantum waves) backwards. This contradicts wave particle duality. We will present empirical evidence that wave particle duality is wrong about the direction of particles versus waves. This involves a paradigm shift; which are always controversial. We believe that our model is the ONLY proposal ever made for the physical foundations of probability amplitudes. We will show that our ``probability amplitudes'' in physical nature form a Hilbert vector space with adjoints, an inner product and support both linear algebra and Dirac notation.

Altered resting brain function and structure in professional badminton players.

Science.gov (United States)

Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

2012-01-01

Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

Measurement of amplitude fluctuations in a rapid response photomultiplier; Mesure des fluctuations d'amplitude d'un photo multiplicateur a reponse rapide

Energy Technology Data Exchange (ETDEWEB)

Raimbault, P [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1961-07-01

In order to measure amplitude fluctuations in a rapid response photomultiplier, two independent random variables are introduced which determine the shape of the anode pulse. The energy of each pulse, which depends directly on the gain and the variance, is the first variable; amplitude fluctuations, functions of the first variable, depend as well on the pulse width which in turn constitutes the second variable. The results obtained on the variations of the maximum impulse, using a steep-edged pulse broadening circuit, and those obtained on the statistical variations of the gain, are compared to show that the variance relative to the maximum amplitude of the signal is greater than that of the gain. Within the limits of these fluctuations are shown the contribution of the secondary emission coefficient of the first dynode, and that of the mean secondary emission coefficient of the multiplier. (author) [French] Pour etudier les fluctuations d'amplitude d'un photomultiplicateur a reponse rapide, on introduit deux variables aleatoires independantes qui determinent la forme de l'impulsion anodique. L'energie de chaque impulsion, directement fonction du gain et de sa variance, est la premiere variable; les fluctuations d'amplitude, fonctions de la premiere variable, dependent egalement de la largeur de l'impulsion qui, elle, constitue la deuxieme variable. Les resultats obtenus sur les variations de l'amplitude maximale, a l'aide d'un circuit elargisseur d'impulsions a front raide, et les resultats des variations statistiques du gain sont compares pour mettre en evidence le fait que la variance relative a l'amplitude maximale du signal est plus grande que celle du gain. Dans la mesure de ces fluctuations, sont mises en evidence la contribution du coefficient d'emission secondaire de la premiere dynode et celle du coefficient d'emission secondaire moyen du multiplicateur. (auteur)

Basic perceptual changes that alter meaning and neural correlates of recognition memory

Directory of Open Access Journals (Sweden)

Chuanji eGao

2015-02-01

Full Text Available It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not. Abstract visual shapes (squiggles were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400, indicating that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition. Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates

Reinforcing Saccadic Amplitude Variability

Science.gov (United States)

Paeye, Celine; Madelain, Laurent

2011-01-01

Saccadic endpoint variability is often viewed as the outcome of neural noise occurring during sensorimotor processing. However, part of this variability might result from operant learning. We tested this hypothesis by reinforcing dispersions of saccadic amplitude distributions, while maintaining constant their medians. In a first experiment we…

Muscarinic acetylcholine receptor expression in aganglionic bowel.

Science.gov (United States)

Oue, T; Yoneda, A; Shima, H; Puri, P

2000-01-01

In Hirschsprung's disease (HD) there exists an overabundance of acetylcholine (ACh), which in turn stimulates excessive production of the enzyme acetylcholinesterase. Muscarinic ACh receptors (mAChRs) play an important role in smooth-muscle contraction. Recent studies have indicated five different subtypes of mAChRs encoded by five different genes, ml to m5. The purpose of this study was to investigate the expression of each mAChR subtype in aganglionic (AG) colon to further understand the pathophysiology of HD. Entire colon resected at the time of pull-through operation for HD was obtained from 14 patients. Specimens obtained at autopsy from 8 age-matched patients without gastrointestinal disease acted as controls. Frozen sections were used for indirect immunohistochemistry as well as in-situ hybridization. Immunohistochemistry was performed using specific antiserum against each mAChR subtype and in-situ hybridization was performed using specific oligonucleotide probes against ml to m5 subtypes. Messenger RNA (mRNA) was extracted from normoganglionic (NG) and AG bowel of HD patients and normal control bowel. Reverse transcription-polymerase chain reaction was performed to evaluate mRNA levels of each mAChR subtype. To adjust the levels of mRNA expression, a housekeeping gene G3PDH, known to be expressed normally, was used as an internal control. Strong m2 and m3 immunoreactivity was observed in the mucosal layer, smooth-muscle layers, and myenteric plexus of NG bowel, whereas ml immunoreactivity was only detected in the mucosal layer. The most striking finding was the abundance of m3-immunoreactive fibers in muscle layers of NG bowel while there was a total lack of m3 fibers in smooth-muscle of AG bowel. Intense mRNA signals encoding m2 and m3 and to a lesser degree ml were detected in NG bowel, and these signals were weak in AG bowel. Immunoreactivity and mRNA expression of m4 and m5 was not detected in NG or AG bowel. The lack of m3-immunoreactive fibers in the

Miracles in Scattering Amplitudes: from QCD to Gravity

Energy Technology Data Exchange (ETDEWEB)

Volovich, Anastasia [Brown Univ., Providence, RI (United States)

2016-10-09

The goal of my research project "Miracles in Scattering Amplitudes: from QCD to Gravity" involves deepening our understanding of gauge and gravity theories by exploring hidden structures in scattering amplitudes and using these rich structures as much as possible to aid practical calculations.

High energy multi-gluon exchange amplitudes

International Nuclear Information System (INIS)

Jaroszewicz, T.

1980-11-01

We examine perturbative high energy n-gluon exchange amplitudes calculated in the Coulomb gauge. If n exceeds the minimum required by the t-channel quantum numbers, such amplitudes are non-leading in lns. We derive a closed system of coupled integral equations for the corresponding two-particle n-gluon vertices, obtained by summing the leading powers of ln(N μ psup(μ)), where psup(μ) is the incident momentum and Nsup(μ) the gauge-defining vector. Our equations are infra-red finite, provided the external particles are colour singlets. (author)

Precise generator of stability amplitude pulses

International Nuclear Information System (INIS)

Zhuk, N.A.; Zdesenko, Yu.G.; Kuts, V.N.

1989-01-01

A generator of stability amplitude pulses, designed for stabilization of a low-noise semiconducting spectrometer, used in investigations of 76 Ge2β-decay, is described. The generator contains a permanent-voltage source, a storage element and a switch based on a Hg relay. A thermostatic source provides a relative voltage instability less than ±5x10 -6 per 80h (standard deviation). The Hg relay is placed into a separate thermostat. The relative instability of output generator pulse amplitude does not exceed ±1.5x10 -5 per 24h

Enhancement of Extinction Learning Attenuates Ethanol-Seeking Behavior and Alters Plasticity in the Prefrontal Cortex

Science.gov (United States)

Trantham-Davidson, Heather; Kassab, Amanda S.; Glen, William B.; Olive, M. Foster; Chandler, L. Judson

2014-01-01

Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. PMID:24872560

Direct amplitude detuning measurement with ac dipole

Directory of Open Access Journals (Sweden)

S. White

2013-07-01

Full Text Available In circular machines, nonlinear dynamics can impact parameters such as beam lifetime and could result in limitations on the performance reach of the accelerator. Assessing and understanding these effects in experiments is essential to confirm the accuracy of the magnetic model and improve the machine performance. A direct measurement of the machine nonlinearities can be obtained by characterizing the dependency of the tune as a function of the amplitude of oscillations (usually defined as amplitude detuning. The conventional technique is to excite the beam to large amplitudes with a single kick and derive the tune from turn-by-turn data acquired with beam position monitors. Although this provides a very precise tune measurement it has the significant disadvantage of being destructive. An alternative, nondestructive way of exciting large amplitude oscillations is to use an ac dipole. The perturbation Hamiltonian in the presence of an ac dipole excitation shows a distinct behavior compared to the free oscillations which should be correctly taken into account in the interpretation of experimental data. The use of an ac dipole for direct amplitude detuning measurement requires careful data processing allowing one to observe the natural tune of the machine; the feasibility of such a measurement is demonstrated using experimental data from the Large Hadron Collider. An experimental proof of the theoretical derivations based on measurements performed at injection energy is provided as well as an application of this technique at top energy using a large number of excitations on the same beam.

Employing helicity amplitudes for resummation in SCET

International Nuclear Information System (INIS)

Moult, Ian; Stewart, Iain W.; Tackmann, Frank J.; Waalewijn, Wouter J.; Nikhef, Amsterdam

2016-05-01

Helicity amplitudes are the fundamental ingredients of many QCD calculations for multi-leg processes. We describe how these can seamlessly be combined with resummation in Soft-Collinear Effective Theory (SCET), by constructing a helicity operator basis for which the Wilson coefficients are directly given in terms of color-ordered helicity amplitudes. This basis is crossing symmetric and has simple transformation properties under discrete symmetries.

The Cepheid bump progression and amplitude equations

International Nuclear Information System (INIS)

Kovacs, G.; Buchler, J.R.

1989-01-01

It is shown that the characteristic and systematic behavior of the low-order Fourier amplitudes and phases of hydrodynamically generated radial velocity and light curves of Cepheid model sequences is very well captured not only qualitatively but also quantitatively by the amplitude equation formalism. The 2:1 resonance between the fundamental and the second overtone plays an essential role in the behavior of the models 8 refs

Study of inelastic decay of amplitudes in 49V

International Nuclear Information System (INIS)

Chou, B.H.

1980-01-01

Inelastic decay amplitudes from d-wave resonances in 49 V were obtained for 80 resonances in the proton energy range 2.2 to 3.1 MeV. With the 3 MV Van de Graaff accelerator and high resolution system at the Triangle Universities Nuclear Laboratory, an overall resolution of 350 eV was obtained. The experiment consisted of measurements of the angular distributions of the inelastically scattered protons and the subsequent deexcitation gamma rays. Forty five resonances were assigned J/sup π/ = 5/2 + , while thirty five resonances were assigned 3/2 + . The magnitudes of three inelastic decay amplitudes and the relative signs between these three amplitudes were determined. Large amplitude correlations were observed; the data are in the striking disagreement with the extreme statistical model. The present results provide the first explicit test of the multivariate reduced width amplitude distribution of Krieger and Porter; the agreement is excellent. The physical origin of these channel correlations has not yet been explained

Two-Loop Gluon to Gluon-Gluon Splitting Amplitudes in QCD

International Nuclear Information System (INIS)

Bern, Z.

2004-01-01

Splitting amplitudes are universal functions governing the collinear behavior of scattering amplitudes for massless particles. We compute the two-loop g → gg splitting amplitudes in QCD, N = 1, and N = 4 super-Yang-Mills theories, which describe the limits of two-loop n-point amplitudes where two gluon momenta become parallel. They also represent an ingredient in a direct x-space computation of DGLAP evolution kernels at next-to-next-to-leading order. To obtain the splitting amplitudes, we use the unitarity sewing method. In contrast to the usual light-cone gauge treatment, our calculation does not rely on the principal-value or Mandelstam-Leibbrandt prescriptions, even though the loop integrals contain some of the denominators typically encountered in light-cone gauge. We reduce the integrals to a set of 13 master integrals using integration-by-parts and Lorentz invariance identities. The master integrals are computed with the aid of differential equations in the splitting momentum fraction z. The ε-poles of the splitting amplitudes are consistent with a formula due to Catani for the infrared singularities of two-loop scattering amplitudes. This consistency essentially provides an inductive proof of Catani's formula, as well as an ansatz for previously-unknown 1/ε pole terms having non-trivial color structure. Finite terms in the splitting amplitudes determine the collinear behavior of finite remainders in this formula

Tensor exchange amplitudes in K +- N charge exchange reactions

International Nuclear Information System (INIS)

Svec, M.

1979-01-01

Tensor (A 2 ) exchange amplitudes in K +- N charge exchange (CEX) are constructed from the K +- N CEX data supplemented by information on the vector (rho) exchange amplitudes from πN sca tering. We observed new features in the t-structure of A 2 exchange amplitudes which contradict the t-de pendence anticipated by most of the Regge models. The results also provide evidence for violation of weak exchange degeneracy

Ambitwistor strings and reggeon amplitudes in N=4 SYM

Directory of Open Access Journals (Sweden)

L.V. Bork

2017-11-01

Full Text Available We consider the description of reggeon amplitudes (Wilson lines form factors in N=4 SYM within the framework of four dimensional ambitwistor string theory. The latter is used to derive scattering equations representation for reggeon amplitudes with multiple reggeized gluons present. It is shown, that corresponding tree-level string correlation function correctly reproduces previously obtained Grassmannian integral representation of reggeon amplitudes in N=4 SYM.

In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide

International Nuclear Information System (INIS)

Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr.

1991-01-01

Two [ 18 F]-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-[ 18 F]- or 4-[ 18 F]-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies

Heptagon amplitude in the multi-Regge regime

International Nuclear Information System (INIS)

Bartels, J.

2014-05-01

As we have shown in previous work, the high energy limit of scattering amplitudes in N=4 supersymmetric Yang-Mills theory corresponds to the infrared limit of the 1-dimensional quantum integrable system that solves minimal area problems in AdS 5 . This insight can be developed into a systematic algorithm to compute the strong coupling limit of amplitudes in the multi-Regge regime through the solution of auxiliary Bethe Ansatz equations. We apply this procedure to compute the scattering amplitude for n=7 external gluons in different multi-Regge regions at infinite 't Hooft coupling. Our formulas are remarkably consistent with the expected form of 7-gluon Regge cut contributions in perturbative gauge theory. A full description of the general algorithm and a derivation of results is given in a forthcoming paper.

Scaling of saturation amplitudes in baroclinic instability

International Nuclear Information System (INIS)

Shepherd, T.G.

1994-01-01

By using finite-amplitude conservation laws for pseudomomentum and pseudoenergy, rigorous upper bounds have been derived on the saturation amplitudes in baroclinic instability for layered and continuously-stratified quasi-geostrophic models. Bounds have been obtained for both the eddy energy and the eddy potential enstrophy. The bounds apply to conservative (inviscid, unforced) flow, as well as to forced-dissipative flow when the dissipation is proportional to the potential vorticity. This approach provides an efficient way of extracting an analytical estimate of the dynamical scalings of the saturation amplitudes in terms of crucial non-dimensional parameters. A possible use is in constructing eddy parameterization schemes for zonally-averaged climate models. The scaling dependences are summarized, and compared with those derived from weakly-nonlinear theory and from baroclinic-adjustment estimates

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.

N=4 Scattering Amplitudes and the Deformed Graßmannian

CERN Document Server

Ferro, Livia; Staudacher, Matthias

2014-01-01

Some time ago the general tree-level scattering amplitudes of N=4 Super Yang-Mills theory were expressed as certain Grassmannian contour integrals. These remarkable formulas allow to clearly expose the super-conformal, dual super-conformal, and Yangian symmetries of the amplitudes. Using ideas from integrability it was recently shown that the building blocks of the amplitudes permit a natural multi-parameter deformation. However, this approach had been criticized by the observation that it seemed impossible to reassemble the building blocks into Yangian-invariant deformed non-MHV amplitudes. In this note we demonstrate that the deformations may be succinctly summarized by a simple modification of the measure of the Grassmannian integrals, leading to a Yangian-invariant deformation of the general tree-level amplitudes. Interestingly, the deformed building-blocks appear as residues of poles in the spectral parameter planes. Given that the contour integrals also contain information on the amplitudes at loop-leve...

Transversity Amplitudes in Hypercharge Exchange Processes

International Nuclear Information System (INIS)

Aguilar Benitez de Lugo, M.

1979-01-01

' In this work we present several techniques developed for the extraction of the. Transversity amplitudes governing quasi two-body meson baryon reactions with hypercharge exchange. We review the methods used in processes having a pure spin configuration, as well as the more relevant results obtained with data from K p and Tp interactions at intermediate energies. The predictions of the additive quark model and the ones following from exchange degeneracy and etoxicity are discussed. We present a formalism for amplitude analysis developed for reactions with mixed spin configurations and discuss the methods of parametric estimation of the moduli and phases of the amplitudes, as well as the various tests employed to check the goodness of the fits. The calculation of the generalized joint density matrices is given and we propose a method based on the generalization of the idea of multipole moments, which allows to investigate the structure of the decay angular correlations and establishes the quality of the fits and the validity of the simplifying assumptions currently used in this type of studies. (Author) 43 refs

The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia.

Science.gov (United States)

Ding, Zhaofeng; Li, Jinrong; Spiegel, Daniel P; Chen, Zidong; Chan, Lily; Luo, Guangwei; Yuan, Junpeng; Deng, Daming; Yu, Minbin; Thompson, Benjamin

2016-01-14

Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia.

The open superstring 6-point amplitude with manifest symmetries

International Nuclear Information System (INIS)

Barreiro, Luiz Antonio; Medina, Ricardo; Stieberger, Stephan

2011-01-01

Full text: The general tree level amplitude for massless bosons states of open superstrings has been known for a long time ago. It is clear how to obtain this general formula using vertex operators in the Ramond-Neveu-Schwarz formalism. From the beginning of the eighties the explicit expression for this formula has been known in the case of 3 and 4-point amplitudes. In that decade an attempt (with partial success) was done, by Kitazawa, to obtain the corresponding 5-point amplitude. Only in 2002 a complete and correct expression for this amplitude was obtained. Its low energy expansion was compared to the corresponding one from the low energy effective Lagrangian of the open superstring, finding a perfect match. A few years later, in 2005, it was realized that the 5-point formula could be written in a very much compact form, as a sum of two terms: each of them consisting of a momentum factor and a kinematic expression. This constituted a generalization of the 4-point amplitude case, which had been known to be cast in only one momentum factor multiplied by one kinematic expression. For this simplification to happen, known symmetries of the (tree level) scattering amplitudes were implemented in a manifest form. These symmetries are (on-shell) gauge symmetry, cyclic symmetry and twisting symmetry (or world sheet parity). In the recent years it has been realized that the N-point amplitude can be written as a sum of (N - 3)! terms (where N > 3). This result not only agrees with the 3, 4 and 5-point results, but also with the 6-point result which had been obtained by 2005, written as a sum of six terms. The expression that up to now has been obtained for the 6-point amplitude is quite complicated and, besides knowing that it consists of six terms, is not very illuminating. In this work we report on the recent result of writing the 6-point amplitude with gauge, cyclic and twisting symmetries manifest. Not only because of the manifest symmetries this result is important

Tree-level disk amplitude of three closed strings

Science.gov (United States)

Mousavi, Sepideh; Velni, Komeil Babaei

2018-05-01

It has been shown that the disk-level S-matrix elements of one Ramond-Ramond (RR) and two Neveu-Schwarz-Neveu-Schwarz (NSNS) states could be found by applying the Ward identity associated with the string duality and the gauge symmetry on a given component of the S matrix. These amplitudes have appeared as the components of six different T-dual multiplets. It is predicted in the literature that there are some nonzero disk-level scattering amplitudes, such as one RR (p -1 ) form with zero transverse index and two N S N S states, could not be captured by the T-dual Ward identity. We explicitly find this amplitude in terms of a minimal context of the integral functions by the insertion of one closed string RR vertex operator and two NSNS vertex operators. From the amplitude invariance under the Ward identity associated with the NSNS gauge transformations and T-duality, we also find some integral identities.

Laser beam complex amplitude measurement by phase diversity.

Science.gov (United States)

Védrenne, Nicolas; Mugnier, Laurent M; Michau, Vincent; Velluet, Marie-Thérèse; Bierent, Rudolph

2014-02-24

The control of the optical quality of a laser beam requires a complex amplitude measurement able to deal with strong modulus variations and potentially highly perturbed wavefronts. The method proposed here consists in an extension of phase diversity to complex amplitude measurements that is effective for highly perturbed beams. Named camelot for Complex Amplitude MEasurement by a Likelihood Optimization Tool, it relies on the acquisition and processing of few images of the beam section taken along the optical path. The complex amplitude of the beam is retrieved from the images by the minimization of a Maximum a Posteriori error metric between the images and a model of the beam propagation. The analytical formalism of the method and its experimental validation are presented. The modulus of the beam is compared to a measurement of the beam profile, the phase of the beam is compared to a conventional phase diversity estimate. The precision of the experimental measurements is investigated by numerical simulations.

N-loop string amplitude

International Nuclear Information System (INIS)

Mandelstam, S.

1986-06-01

Work on the derivation of an explicit perturbation series for string and superstring amplitudes is reviewed. The light-cone approach is emphasized, but some work on the Polyakov approach is also mentioned, and the two methods are compared. The calculation of the measure factor is outlined in the interacting-string picture

Loop Amplitudes in Pure Yang-Mills from Generalised Unitarity

OpenAIRE

Brandhuber, Andreas; McNamara, Simon; Spence, Bill; Travaglini, Gabriele

2005-01-01

We show how generalised unitarity cuts in D = 4 - 2 epsilon dimensions can be used to calculate efficiently complete one-loop scattering amplitudes in non-supersymmetric Yang-Mills theory. This approach naturally generates the rational terms in the amplitudes, as well as the cut-constructible parts. We test the validity of our method by re-deriving the one-loop ++++, -+++, --++, -+-+ and +++++ gluon scattering amplitudes using generalised quadruple cuts and triple cuts in D dimensions.

Loop amplitudes in pure Yang-Mills from generalised unitarity

International Nuclear Information System (INIS)

Brandhuber, Andreas; McNamara, Simon; Spence, Bill; Travaglini, Gabriele

2005-01-01

We show how generalised unitarity cuts in D = 4-2ε dimensions can be used to calculate efficiently complete one-loop scattering amplitudes in non-supersymmetric Yang-Mills theory. This approach naturally generates the rational terms in the amplitudes, as well as the cut-constructible parts. We test the validity of our method by re-deriving the one-loop ++++, -+++, --++, -+-+ and +++++ gluon scattering amplitudes using generalised quadruple cuts and triple cuts in D dimensions

Loop amplitudes in pure Yang-Mills from generalised unitarity

Energy Technology Data Exchange (ETDEWEB)

Brandhuber, Andreas [Department of Physics, Queen Mary, University of London, Mile End Road, London, E1 4NS (United Kingdom); McNamara, Simon [Department of Physics, Queen Mary, University of London, Mile End Road, London, E1 4NS (United Kingdom); Spence, Bill [Department of Physics, Queen Mary, University of London, Mile End Road, London, E1 4NS (United Kingdom); Travaglini, Gabriele [Department of Physics, Queen Mary, University of London, Mile End Road, London, E1 4NS (United Kingdom)

2005-10-15

We show how generalised unitarity cuts in D = 4-2{epsilon} dimensions can be used to calculate efficiently complete one-loop scattering amplitudes in non-supersymmetric Yang-Mills theory. This approach naturally generates the rational terms in the amplitudes, as well as the cut-constructible parts. We test the validity of our method by re-deriving the one-loop ++++, -+++, --++, -+-+ and +++++ gluon scattering amplitudes using generalised quadruple cuts and triple cuts in D dimensions.

Changes in motor unit recruitment strategy during pain alters force direction.

Science.gov (United States)

Tucker, Kylie J; Hodges, Paul W

2010-10-01

Motor unit (MU) recruitment is altered (decreased discharge rate and cessation of discharge in some units, and recruitment of new units) in force-matched contractions during pain compared to contractions performed before pain. As MU's within a motoneurone pool have different force direction properties we hypothesised that altered MU recruitment during experimental knee pain would change the force vector (total force (F(T)): amplitude and angle) generated by the quadriceps. Force was produced at two levels during 1 × 60-s and 3 × 10-s isometric contractions of knee extensors, and recorded by two force transducers at right angles. This enabled calculation of both F(E) (extension force) and F(T). MU recruitment was recorded from the medial and lateral vastii with four fine-wire electrodes. Pain was induced by hypertonic saline injection in the infra-patella fat pad. Nine subjects matched F(E) and six subjects also matched both medial and lateral forces (F(T)) before and during pain. Changes in MU discharge pattern (decreased discharge rate (Precruitment of new units) during pain were associated with a ∼5° change in absolute force angle. As force angle changed in both directions (left/right) for individual subjects with pain there was no change in average F(T) amplitude between conditions. When both medial and lateral forces were matched MU discharge rate decreased (Punits ceased firing or were newly recruited during pain. Change in motoneurone recruitment during pain alters direction of muscle force. This may be a strategy to avoid pain or protect the painful part. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Generating tree amplitudes in N = 4 SYM and N = 8 SG

International Nuclear Information System (INIS)

Bianchi, Massimo; Elvang, Henriette; Freedman, Daniel Z.

2008-01-01

We study n-point tree amplitudes of N = 4 super Yang-Mills theory and N = 8 supergravity for general configurations of external particles of the two theories. We construct generating functions for n-point MHV and NMHV amplitudes with general external states. Amplitudes derived from them obey SUSY Ward identities, and the generating functions characterize and count amplitudes in the MHV and NMHV sectors. The MHV generating function provides an efficient way to perform the intermediate state helicity sums required to obtain loop amplitudes from trees. The NMHV generating functions rely on the MHV-vertex expansion obtained from recursion relations associated with a 3-line shift of external momenta involving a reference spinor |X]. When the shifted amplitude vanishes for large z for all |X], the sum of MHV-vertex diagrams is independent of |X] and gives the correct amplitude. If the shifted amplitude does not vanish for large z, Cauchy's theorem includes a term at infinity. Examples show that special choices of |X] eliminate this term and the MHV vertex expansion becomes valid at these values. We show that the MHV-vertex expansion of the n-graviton NMHV amplitude for n = 5,6,...,11 is independent of |X] and exhibits the asymptotic behavior z n-12 . Generating functions show how the symmetries of supergravity can be implemented in the quadratic map between supergravity and gauge theory embodied in the KLT and other similar relations between amplitudes in the two theories.

Altered intrinsic brain activities in patients with acute eye pain using amplitude of low-frequency fluctuation: a resting-state fMRI study

Directory of Open Access Journals (Sweden)

Pan Z

2018-01-01

Full Text Available Zhi-Ming Pan,1 Hai-Jun Li,1 Jing Bao,1 Nan Jiang,1 Qing Yuan,1 Shelby Freeberg,2 Pei-Wen Zhu,1 Lei Ye,1 Ming-Yang Ma,1 Xin Huang,1 Yi Shao1 1Department of Ophthalmology and Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, University of Florida, Gainesville, FL, USA Objective: Many previous studies have reported that pain symptoms can lead to significant brain function and anatomical changes, whereas the intrinsic brain activity changes in acute eye pain (EP patients remain unknown. Using the amplitude of low-frequency fluctuation (ALFF method, this study aimed to evaluate the spontaneous brain activity alterations and their relationships with clinical features in acute EP patients.Participants and methods: A total of 20 patients with EP (15 males and 5 females and 20 healthy controls (HCs; 15 males and 5 females closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was applied to assess spontaneous brain activity changes. The ALFF values of the EP patients were distinguished from those of the HCs using a receiver operating characteristic curve. Pearson’s correlation analysis was used to investigate the relationships between the mean ALFF signal values from many brain regions and the clinical features in EP patients.Results: Compared with the HCs, acute EP patients had significantly lower ALFF in the left and right precentral/postcentral gyrus and left precuneus. In contrast, acute EP patients showed higher ALFF values in the right and left parahippocampal gyri and left caudate. However, no relationship was observed between the mean ALFF signal values from the different areas and clinical manifestations in the acute EP patients.Conclusion: We demonstrated that acute EP patients showed abnormal intrinsic brain activities in the precentral/postcentral gyrus and limbic system

Monodromy relations in higher-loop string amplitudes

Directory of Open Access Journals (Sweden)

S. Hohenegger

2017-12-01

Full Text Available New monodromy relations of loop amplitudes are derived in open string theory. We particularly study N-point (planar and non-planar one-loop amplitudes described by a world-sheet cylinder and derive a set of relations between subamplitudes of different color orderings. Various consistency checks are performed by matching α′-expansions of planar and non-planar amplitudes involving elliptic iterated integrals with the resulting periods giving rise to two sets of multiple elliptic zeta values. The latter refer to the two homology cycles on the once-punctured complex elliptic curve and the monodromy equations provide relations between these two sets of multiple elliptic zeta values. Furthermore, our monodromy relations involve new objects for which we present a tentative interpretation in terms of open string scattering amplitudes in the presence of a non-trivial gauge field flux. Finally, we provide an outlook on how to generalize the new monodromy relations to the non-oriented case and beyond the one-loop level. Comparing a subset of our results with recent findings in the literature we find therein several serious issues related to the structure and significance of monodromy phases and the relevance of missed contributions from contour integrations.

Some tree-level string amplitudes in the NSR formalism

International Nuclear Information System (INIS)

Becker, Katrin; Becker, Melanie; Melnikov, Ilarion V.; Robbins, Daniel; Royston, Andrew B.

2015-01-01

We calculate tree level scattering amplitudes for open strings using the NSR formalism. We present a streamlined symmetry-based and pedagogical approach to the computations, which we first develop by checking two-, three-, and four-point functions involving bosons and fermions. We calculate the five-point amplitude for massless gluons and find agreement with an earlier result by Brandt, Machado and Medina. We then compute the five-point amplitudes involving two and four fermions respectively, the general form of which has not been previously obtained in the NSR formalism. The results nicely confirm expectations from the supersymmetric F 4 effective action. Finally we use the prescription of Kawai, Lewellen and Tye (KLT) to compute the amplitudes for the closed string sector.

On-shell recurrence relations for one-loop QCD amplitudes

International Nuclear Information System (INIS)

Bern, Zvi; Dixon, Lance J.; Kosower, David A.

2005-01-01

We present examples of on-shell recurrence relations for determining rational functions appearing in one-loop QCD amplitudes. In particular, we give relations for one-loop QCD amplitudes with all legs of positive helicity, or with one leg of negative helicity and the rest of positive helicity. Our recurrence relations are similar to the tree-level ones described by Britto, Cachazo, Feng, and Witten. A number of new features arise for loop amplitudes in nonsupersymmetric theories like QCD, including boundary terms and double poles. We show how to eliminate the boundary terms, which would interfere with obtaining useful relations. Using the relations we give compact explicit expressions for the n-gluon amplitudes with one negative-helicity gluon, up through n=7

Scattering Amplitudes and Worldsheet Models of QFTs

CERN Multimedia

CERN. Geneva

2016-01-01

I will describe recent progress on the study of scattering amplitudes via ambitwistor strings and the scattering equations. Ambitwistor strings are worldsheet models of quantum field theories, inspired by string theory. They naturally lead to a representation of amplitudes based on the scattering equations. While worldsheet models and related ideas have had a wide-ranging impact on the modern study of amplitudes, their direct application at loop level is a very recent success. I will show how a major difficulty in the loop-level story, the technicalities of higher-genus Riemann surfaces, can be avoided by turning the higher-genus surface into a nodal Riemann sphere, with the nodes representing the loop momenta. I will present new formulas for the one-loop integrands of gauge theory and gravity, with or without supersymmetry, and also some two-loop results.

Multiphoton amplitude in a constant background field

Science.gov (United States)

Ahmad, Aftab; Ahmadiniaz, Naser; Corradini, Olindo; Kim, Sang Pyo; Schubert, Christian

2018-01-01

In this contribution, we present our recent compact master formulas for the multiphoton amplitudes of a scalar propagator in a constant background field using the worldline fomulation of quantum field theory. The constant field has been included nonperturbatively, which is crucial for strong external fields. A possible application is the scattering of photons by electrons in a strong magnetic field, a process that has been a subject of great interest since the discovery of astrophysical objects like radio pulsars, which provide evidence that magnetic fields of the order of 1012G are present in nature. The presence of a strong external field leads to a strong deviation from the classical scattering amplitudes. We explicitly work out the Compton scattering amplitude in a magnetic field, which is a process of potential relevance for astrophysics. Our final result is compact and suitable for numerical integration.

Gluon cascades and amplitudes in light-front perturbation theory

International Nuclear Information System (INIS)

Cruz-Santiago, C.A.; Staśto, A.M.

2013-01-01

We construct the gluon wave functions, fragmentation functions and scattering amplitudes within the light-front perturbation theory. Recursion relations on the light-front are constructed for the wave functions and fragmentation functions, which in the latter case are the light-front analogs of the Berends–Giele recursion relations. Using general relations between wave functions and scattering amplitudes it is demonstrated how to obtain the maximally-helicity violating amplitudes, and explicit verification of the results is based on simple examples.

Iterative structure within the five-particle two-loop amplitude

International Nuclear Information System (INIS)

Cachazo, Freddy; Spradlin, Marcus; Volovich, Anastasia

2006-01-01

We find an unexpected iterative structure within the two-loop five-gluon amplitude in N=4 supersymmetric Yang-Mills theory. Specifically, we show that a subset of diagrams contributing to the full amplitude, including a two-loop pentagon-box integral with nontrivial dependence on five kinematical variables, satisfies an iterative relation in terms of one-loop scalar box diagrams. The implications of this result for the possible iterative structure of the full two-loop amplitude are discussed

Top quark amplitudes with an anomalous magnetic moment

International Nuclear Information System (INIS)

Larkoski, Andrew J.; Peskin, Michael E.

2011-01-01

The anomalous magnetic moment of the top quark may be measured during the first run of the LHC at 7 TeV. For these measurements, it will be useful to have available tree amplitudes with tt and arbitrarily many photons and gluons, including both QED and color anomalous magnetic moments. In this paper, we present a method for computing these amplitudes using the Britto-Cachazo-Feng-Witten recursion formula. Because we deal with an effective theory with higher-dimension couplings, there are roadblocks to a direct computation with the Britto-Cachazo-Feng-Witten method. We evade these by using an auxiliary scalar theory to compute a subset of the amplitudes.

Effective gluon interactions from superstring disk amplitudes

International Nuclear Information System (INIS)

Oprisa, D.

2006-05-01

In this thesis an efficient method for the calculation of the N-point tree-level string amplitudes is presented. Furthermore it is shown that the six-gluon open-superstring disk amplitude can be expressed by a basis of six triple hypergeometric functions, which encode the full α' dependence. In this connection material for obtaining the α' expansion of these functions is derived. Hereby many Euler-Zagier sums are calculated including multiple harmonic series. (HSI)

Generating Tree Amplitudes in $N$=4 SYM and $N$ = 8 SG

CERN Document Server

Bianchi, Massimo; Freedman, Daniel Z

2008-01-01

We study n-point tree amplitudes of N=4 super Yang-Mills theory and N=8 supergravity for general configurations of external particles of the two theories. We construct generating functions for n-point MHV and NMHV amplitudes with general external states. Amplitudes derived from them obey SUSY Ward identities, and the generating functions characterize and count amplitudes in the MHV and NMHV sectors. The MHV generating function provides an efficient way to perform the intermediate state helicity sums required to obtain loop amplitudes from trees. The NMHV generating functions rely on the MHV-vertex expansion obtained from recursion relations associated with a 3-line shift of external momenta involving a reference spinor |X]. The recursion relations remain valid for a subset of N=8 supergravity amplitudes although they do not vanish asymptotically for all |X]. The MHV-vertex expansion of the n-graviton NMHV amplitude for n=5,6,...,11 is independent of |X] and exhibits the asymptotic behavior z^{n-12}. This pres...

Damage accumulation of bovine bone under variable amplitude loads

Directory of Open Access Journals (Sweden)

Abbey M. Campbell

2016-12-01

Full Text Available Stress fractures, a painful injury, are caused by excessive fatigue in bone. This study on damage accumulation in bone sought to determine if the Palmgren-Miner rule (PMR, a well-known linear damage accumulation hypothesis, is predictive of fatigue failure in bone. An electromagnetic shaker apparatus was constructed to conduct cyclic and variable amplitude tests on bovine bone specimens. Three distinct damage regimes were observed following fracture. Fractures due to a low cyclic amplitude loading appeared ductile (4000 μϵ, brittle due to high cyclic amplitude loading (>9000 μϵ, and a combination of ductile and brittle from mid-range cyclic amplitude loading (6500 –6750 μϵ. Brittle and ductile fracture mechanisms were isolated and mixed, in a controlled way, into variable amplitude loading tests. PMR predictions of cycles to failure consistently over-predicted fatigue life when mixing isolated fracture mechanisms. However, PMR was not proven ineffective when used with a single damage mechanism. Keywords: Bone fatigue, Bone fracture, Health system monitoring, Failure prediction

Disappearance of Anisotropic Intermittency in Large-amplitude MHD Turbulence and Its Comparison with Small-amplitude MHD Turbulence

Science.gov (United States)

Yang, Liping; Zhang, Lei; He, Jiansen; Tu, Chuanyi; Li, Shengtai; Wang, Xin; Wang, Linghua

2018-03-01

Multi-order structure functions in the solar wind are reported to display a monofractal scaling when sampled parallel to the local magnetic field and a multifractal scaling when measured perpendicularly. Whether and to what extent will the scaling anisotropy be weakened by the enhancement of turbulence amplitude relative to the background magnetic strength? In this study, based on two runs of the magnetohydrodynamic (MHD) turbulence simulation with different relative levels of turbulence amplitude, we investigate and compare the scaling of multi-order magnetic structure functions and magnetic probability distribution functions (PDFs) as well as their dependence on the direction of the local field. The numerical results show that for the case of large-amplitude MHD turbulence, the multi-order structure functions display a multifractal scaling at all angles to the local magnetic field, with PDFs deviating significantly from the Gaussian distribution and a flatness larger than 3 at all angles. In contrast, for the case of small-amplitude MHD turbulence, the multi-order structure functions and PDFs have different features in the quasi-parallel and quasi-perpendicular directions: a monofractal scaling and Gaussian-like distribution in the former, and a conversion of a monofractal scaling and Gaussian-like distribution into a multifractal scaling and non-Gaussian tail distribution in the latter. These results hint that when intermittencies are abundant and intense, the multifractal scaling in the structure functions can appear even if it is in the quasi-parallel direction; otherwise, the monofractal scaling in the structure functions remains even if it is in the quasi-perpendicular direction.

Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

Science.gov (United States)

Rattmann, Yanna D; Crestani, Sandra; Lapa, Fernanda R; Miguel, Obdúlio G; Marques, Maria C A; da Silva-Santos, J Eduardo; Santos, Adair R S

2009-01-01

Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.

Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Shinotoh, H; Asahina, M; Hirayama, K [Dept. of Neurology, School of Medicine, Chiba Univ., Chiba (Japan); Inoue, O; Suhara, T; Tateno, Y [Division of Clinical Research, National Inst. of Radiological Sciences, Chiba (Japan)

1994-01-01

The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([[sup 11]C]NMPB). [[sup 11]C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n=5) or 400 mg of L-dopa with 57 mg of benserazide (n=2) on the binding parameter of mAChRs (K[sub 3]). There was a mean 28% inhibition of K[sub 3] values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K[sub 3] was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.

Renormalization in the complete Mellin representation of Feynman amplitudes

International Nuclear Information System (INIS)

Calan, C. de; David, F.; Rivasseau, V.

1981-01-01

The Feynmann amplitudes are renormalized in the formalism of the CM representation. This Mellin-Barnes type integral representation, previously introduced for the study of asymptotic behaviours, is shown to have the following interesting property: in contrast with the usual subtraction procedures, the renormalization leaves the CM intergrand unchanged, and only results into translations of the integration path. The explicit CM representation of the renormalized amplitudes is given. In addition, the dimensional regularization and the extension to spinor amplitudes are sketched. (orig.)

Corrections to the box diagram amplitude due to kaon mass

International Nuclear Information System (INIS)

Datta, A.; Kumbhakar, D.

1985-08-01

The K 0 -anti-K 0 mixing amplitude is calculated without using the standard zero external momentum approximation. The resulting corrections are numerically significant for the real part of the amplitude. In the imaginary part of the amplitude the effects of similar corrections are less important. Implications for Δmsub(k) and epsilon are discussed. (author)

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…

Nonlinear Saturation Amplitude in Classical Planar Richtmyer–Meshkov Instability

International Nuclear Information System (INIS)

Liu Wan-Hai; Jiang Hong-Bin; Ma Wen-Fang; Wang Xiang

2016-01-01

The classical planar Richtmyer–Meshkov instability (RMI) at a fluid interface supported by a constant pressure is investigated by a formal perturbation expansion up to the third order, and then according to definition of nonlinear saturation amplitude (NSA) in Rayleigh–Taylor instability (RTI), the NSA in planar RMI is obtained explicitly. It is found that the NSA in planar RMI is affected by the initial perturbation wavelength and the initial amplitude of the interface, while the effect of the initial amplitude of the interface on the NSA is less than that of the initial perturbation wavelength. Without marginal influence of the initial amplitude, the NSA increases linearly with wavelength. The NSA normalized by the wavelength in planar RMI is about 0.11, larger than that corresponding to RTI. (paper)

Gluon amplitudes as 2 d conformal correlators

Science.gov (United States)

Pasterski, Sabrina; Shao, Shu-Heng; Strominger, Andrew

2017-10-01

Recently, spin-one wave functions in four dimensions that are conformal primaries of the Lorentz group S L (2 ,C ) were constructed. We compute low-point, tree-level gluon scattering amplitudes in the space of these conformal primary wave functions. The answers have the same conformal covariance as correlators of spin-one primaries in a 2 d CFT. The Britto-Cachazo-Feng-Witten (BCFW) recursion relation between three- and four-point gluon amplitudes is recast into this conformal basis.

Effective gluon interactions from superstring disk amplitudes

Energy Technology Data Exchange (ETDEWEB)

Oprisa, D.

2006-05-15

In this thesis an efficient method for the calculation of the N-point tree-level string amplitudes is presented. Furthermore it is shown that the six-gluon open-superstring disk amplitude can be expressed by a basis of six triple hypergeometric functions, which encode the full {alpha}' dependence. In this connection material for obtaining the {alpha}' expansion of these functions is derived. Hereby many Euler-Zagier sums are calculated including multiple harmonic series. (HSI)

Multiphoton states and amplitude k-th power squeezing

International Nuclear Information System (INIS)

Buzek, V.; Jex, I.

1991-01-01

On the basis of the work of d'Ariano and coworkers a new type of multiphoton states is introduced. Amplitude k-th power squeezing of the multiphoton states are analysed. In particular, it is shown that even if the multiphoton states do not exhibit ordinary squeezing they can be amplitude k-th power squeezed

Top Quark Amplitudes with an Anomolous Magnetic Moment

International Nuclear Information System (INIS)

Larkoski, Andrew

2011-01-01

The anomalous magnetic moment of the top quark may be measured during the first run of the LHC at 7 TeV. For these measurements, it will be useful to have available tree amplitudes with t(bar t) and arbitrarily many photons and gluons, including both QED and color anomalous magnetic moments. In this paper, we present a method for computing these amplitudes using the Britto-Cachazo-Feng-Witten recursion formula. Because we deal with an effective theory with higher-dimension couplings, there are roadblocks to a direct computation with the Britto-Cachazo-Feng-Witten method. We evade these by using an auxiliary scalar theory to compute a subset of the amplitudes.

arXiv New relations for graviton-matter amplitudes

CERN Document Server

Plefka, Jan

We present new relations for scattering amplitudes of color ordered gluons, massive quarks and scalars minimally coupled to gravity. Tree-level amplitudes of arbitrary matter and gluon multiplicities involving one graviton are reduced to partial amplitudes in QCD or scalar QCD. The obtained relations are a direct generalization of the recently found Einstein-Yang-Mills relations. The proof of the new relation employs a simple diagrammatic argument trading the graviton-matter couplings to an `upgrade' of a gluon coupling with a color-kinematic replacement rule enforced. The use of the Melia-Johansson-Ochirov color basis is a key element of the reduction. We comment on the generalization to multiple gravitons in the single color trace case.

Calculation and modular properties of multi-loop superstring amplitudes

International Nuclear Information System (INIS)

Danilov, G S

2012-01-01

Multi-loop superstring amplitude is calculated in the conventional gauge where Grassmann moduli are carried by the 2D gravitino field. Generally, instead of the modular symmetry, the amplitudes hold the symmetry under modular transformations added by relevant transformations of the 2D local supersymmetry. If a number of loops are larger than 3, the integration measures are not modular forms. In this case the expression for the amplitude contains an integral over the bound of the fundamental region of the modular group. (paper)

An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP

International Nuclear Information System (INIS)

Oosten, Erik M. van; Wilson, Alan A.; Stephenson, Karin A.; Mamo, David C.; Pollock, Bruce G.; Mulsant, Benoit H.; Yudin, Andrei K.; Houle, Sylvain; Vasdev, Neil

2009-01-01

The radioligand 3-(4-(3-[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([ 18 F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [ 18 F]FP-TZTP, automated using a GE TRACERlab TM FX FN radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [ 18 F]fluoride (K[ 18 F]/K 222 ) in CH 3 CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [ 18 F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29±4%, with a specific activity of 138±41 GBq/μmol (3732±1109 mCi/μmol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported

MHV, CSW and BCFW: field theory structures in string theory amplitudes

International Nuclear Information System (INIS)

Boels, Rutger; Larsen, Kasper Jens; Obers, Niels A.; Vonk, Marcel

2008-01-01

Motivated by recent progress in calculating field theory amplitudes, we study applications of the basic ideas in these developments to the calculation of amplitudes in string theory. We consider in particular both non-Abelian and Abelian open superstring disk amplitudes in a flat space background, focusing mainly on the four-dimensional case. The basic field theory ideas under consideration split into three separate categories. In the first, we argue that the calculation of α'-corrections to MHV open string disk amplitudes reduces to the determination of certain classes of polynomials. This line of reasoning is then used to determine the α' 3 -correction to the MHV amplitude for all multiplicities. A second line of attack concerns the existence of an analog of CSW rules derived from the Abelian Dirac-Born-Infeld action in four dimensions. We show explicitly that the CSW-like perturbation series of this action is surprisingly trivial: only helicity conserving amplitudes are non-zero. Last but not least, we initiate the study of BCFW on-shell recursion relations in string theory. These should appear very naturally as the UV properties of the string theory are excellent. We show that all open four-point string amplitudes in a flat background at the disk level obey BCFW recursion relations. Based on the naturalness of the proof and some explicit results for the five-point gluon amplitude, it is expected that this pattern persists for all higher point amplitudes and for the closed string.

The allosteric site regulates the voltage sensitivity of muscarinic receptors.

Science.gov (United States)

Hoppe, Anika; Marti-Solano, Maria; Drabek, Matthäus; Bünemann, Moritz; Kolb, Peter; Rinne, Andreas

2018-01-01

Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Here, we compared the modulation of M 1 -Rs and M 3 -Rs induced by changes in voltage to their allosteric modulation by chemical compounds. We quantified changes in receptor signaling in single HEK 293 cells with a FRET biosensor for the G q protein cycle. In the presence of ACh, M 1 -R signaling was potentiated by voltage, similarly to positive allosteric modulation by benzyl quinolone carboxylic acid. Conversely, signaling of M 3 -R was attenuated by voltage or the negative allosteric modulator gallamine. Because the orthosteric site is highly conserved among M-Rs, but allosteric sites vary, we constructed "allosteric site" M 3 /M 1 -R chimeras and analyzed their voltage dependencies. Exchanging the entire allosteric sites eliminated the voltage sensitivity of ACh responses for both receptors, but did not affect their modulation by allosteric compounds. Furthermore, a point mutation in M 3 -Rs caused functional uncoupling of the allosteric and orthosteric sites and abolished voltage dependence. Molecular dynamics simulations of the receptor variants indicated a subtype-specific crosstalk between both sites, involving the conserved tyrosine lid structure of the orthosteric site. This molecular crosstalk leads to receptor subtype-specific voltage effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Thrombelastography Early Amplitudes in bleeding and coagulopathic trauma patients

DEFF Research Database (Denmark)

Laursen, Thomas Holst; Meyer, Martin A S; Meyer, Anna Sina P

2018-01-01

BACKGROUND: Early amplitudes in the viscoelastic hemostatic assays Thrombelastography (TEG) and Rotation Thromboelastometry (ROTEM) provide fast results, which is critical in resuscitation of bleeding patients. This study investigated associations between TEG early amplitudes and standard TEG var...

Periodic instantons and scattering amplitudes

International Nuclear Information System (INIS)

Khlebnikov, S.Yu.; Rubakov, V.A.; Tinyakov, P.G.

1991-04-01

We discuss the role of periodic euclidean solutions with two turning points and zero winding number (periodic instantons) in instanton induced processes below the sphaleron energy E sph . We find that the periodic instantons describe certain multiparticle scattering events leading to the transitions between topologically distinct vacua. Both the semiclassical amplitudes and inital and final states of these transitions are determined by the periodic instantons. Furthermore, the corresponding probabilities are maximal among all states of given energy. We show that at E ≤ E sph , the periodic instantons can be approximated by infinite chains of ordinary instantons and anti-instantons, and they naturally emerge as deformations of the zero energy instanton. In the framework of 2d abelian Higgs model and 4d electroweak theory we show, however, that there is not obvious relation between periodic instantons and two-particle scattering amplitudes. (orig.)

General split helicity gluon tree amplitudes in open twistor string theory

Science.gov (United States)

Dolan, Louise; Goddard, Peter

2010-05-01

We evaluate all split helicity gluon tree amplitudes in open twistor string theory. We show that these amplitudes satisfy the BCFW recurrence relations restricted to the split helicity case and, hence, that these amplitudes agree with those of gauge theory. To do this we make a particular choice of the sextic constraints in the link variables that determine the poles contributing to the contour integral expression for the amplitudes. Using the residue theorem to re-express this integral in terms of contributions from poles at rational values of the link variables, which we determine, we evaluate the amplitudes explicitly, regaining the gauge theory results of Britto et al. [25].

A systematic review and meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking.

Science.gov (United States)

Mills, Kathryn; Hunt, Michael A; Leigh, Ryan; Ferber, Reed

2013-08-01

Neuromuscular alterations are increasingly reported in individuals with knee osteoarthritis (KOA) during level walking. We aimed to determine which neuromuscular alterations are consistent in KOA individuals and how these may be influenced by osteoarthritis severity, varus alignment and/or joint laxity. Electronic databases were searched up to July 2012. Cross-sectional observational studies comparing lower-limb neuromuscular activity in individuals with KOA, healthy controls or with different KOA cohorts were included. Two reviewers assessed methodological quality. Effect sizes were used to quantify the magnitude of observed differences. Where studies were homogenous, effect sizes were pooled using a fixed-effects model. Fourteen studies examining neuromuscular alterations in indices of co-contraction, muscle amplitude and muscle activity duration were included. Data pooling revealed that moderate KOA individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64 [0.3 to 0.97]) and moderately increased rectus femoris (ES 0.73 [0.23 to 1.22]), vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to 1.7]) mean amplitude. Non-pooled data indicated prolonged activity of these muscles. Increased medial knee neuromuscular activity was prevalent for those exhibiting varus alignment and medial knee joint laxity. Interpretation Individuals with KOA exhibited increased co-contraction, amplitude and duration of lateral knee muscles regardless of disease severity, limb alignment or medial joint laxity. Individuals with severe disease, varus alignment and medial joint laxity demonstrate up-regulation of medial knee muscles. Future research investigating the efficacy of neuromuscular rehabilitation programs should consider the effect of simultaneous up-regulation of medial and lateral knee muscles on disease progression. © 2013.

The 170ms Response to Faces as Measured by MEG (M170 Is Consistently Altered in Congenital Prosopagnosia.

Directory of Open Access Journals (Sweden)

Andreas Lueschow

Full Text Available Modularity of face processing is still a controversial issue. Congenital prosopagnosia (cPA, a selective and lifelong impairment in familiar face recognition without evidence of an acquired cerebral lesion, offers a unique opportunity to support this fundamental hypothesis. However, in spite of the pronounced behavioural impairment, identification of a functionally relevant neural alteration in congenital prosopagnosia by electrophysiogical methods has not been achieved so far. Here we show that persons with congenital prosopagnosia can be distinguished as a group from unimpaired persons using magnetoencephalography. Early face-selective MEG-responses in the range of 140 to 200ms (the M170 showed prolonged latency and decreased amplitude whereas responses to another category (houses were indistinguishable between subjects with congenital prosopagnosia and unimpaired controls. Latency and amplitude of face-selective EEG responses (the N170 which were simultaneously recorded were statistically indistinguishable between subjects with cPA and healthy controls which resolves heterogeneous and partly conflicting results from existing studies. The complementary analysis of categorical differences (evoked activity to faces minus evoked activity to houses revealed that the early part of the 170ms response to faces is altered in subjects with cPA. This finding can be adequately explained in a common framework of holistic and part-based face processing. Whereas a significant brain-behaviour correlation of face recognition performance and the size of the M170 amplitude is found in controls a corresponding correlation is not seen in subjects with cPA. This indicates functional relevance of the alteration found for the 170ms response to faces in cPA and pinpoints the impairment of face processing to early perceptual stages.

2-vertex Lorentzian spin foam amplitudes for dipole transitions

Science.gov (United States)

Sarno, Giorgio; Speziale, Simone; Stagno, Gabriele V.

2018-04-01

We compute transition amplitudes between two spin networks with dipole graphs, using the Lorentzian EPRL model with up to two (non-simplicial) vertices. We find power-law decreasing amplitudes in the large spin limit, decreasing faster as the complexity of the foam increases. There are no oscillations nor asymptotic Regge actions at the order considered, nonetheless the amplitudes still induce non-trivial correlations. Spin correlations between the two dipoles appear only when one internal face is present in the foam. We compute them within a mini-superspace description, finding positive correlations, decreasing in value with the Immirzi parameter. The paper also provides an explicit guide to computing Lorentzian amplitudes using the factorisation property of SL(2,C) Clebsch-Gordan coefficients in terms of SU(2) ones. We discuss some of the difficulties of non-simplicial foams, and provide a specific criterion to partially limit the proliferation of diagrams. We systematically compare the results with the simplified EPRLs model, much faster to evaluate, to learn evidence on when it provides reliable approximations of the full amplitudes. Finally, we comment on implications of our results for the physics of non-simplicial spin foams and their resummation.

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

OpenAIRE

Qiu, Changjian; Feng, Yuan; Meng, Yajing; Liao, Wei; Huang, Xiaoqi; Lui, Su; Zhu, Chunyan; Chen, Huafu; Gong, Qiyong; Zhang, Wei

2015-01-01

Objective We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD. Methods We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-na?ve adult SAD patients and 19 healthy controls. Voxels wer...

N=4 scattering amplitudes and the deformed Graßmannian

International Nuclear Information System (INIS)

Ferro, Livia; Łukowski, Tomasz; Staudacher, Matthias

2014-01-01

Some time ago the general tree-level scattering amplitudes of N=4 Super Yang–Mills theory were expressed as certain Graßmannian contour integrals. These remarkable formulas allow to clearly expose the super-conformal, dual super-conformal, and Yangian symmetries of the amplitudes. Using ideas from integrability it was recently shown that the building blocks of the amplitudes permit a natural multi-parameter deformation. However, this approach had been criticized by the observation that it seemed impossible to reassemble the building blocks into Yangian-invariant deformed non-MHV amplitudes. In this note we demonstrate that the deformations may be succinctly summarized by a simple modification of the measure of the Graßmannian integrals, leading to a Yangian-invariant deformation of the general tree-level amplitudes. Interestingly, the deformed building blocks appear as residues of poles in the spectral parameter planes. Given that the contour integrals also contain information on the amplitudes at loop-level, we expect the deformations to be useful there as well. In particular, applying meromorphicity arguments, they may be expected to regulate all notorious infrared divergences. We also point out relations to Gelfand hypergeometric functions and the quantum Knizhnik–Zamolodchikov equations

Simplifying Multi-loop Integrands of Gauge Theory and Gravity Amplitudes

Energy Technology Data Exchange (ETDEWEB)

Bern, Z.; Carrasco, J.J.M.; Dixon, L.J.; Johansson, H.; Roiban, R.

2012-02-15

We use the duality between color and kinematics to simplify the construction of the complete four-loop four-point amplitude of N = 4 super-Yang-Mills theory, including the nonplanar contributions. The duality completely determines the amplitude's integrand in terms of just two planar graphs. The existence of a manifestly dual gauge-theory amplitude trivializes the construction of the corresponding N = 8 supergravity integrand, whose graph numerators are double copies (squares) of the N = 4 super-Yang-Mills numerators. The success of this procedure provides further nontrivial evidence that the duality and double-copy properties hold at loop level. The new form of the four-loop four-point supergravity amplitude makes manifest the same ultraviolet power counting as the corresponding N = 4 super-Yang-Mills amplitude. We determine the amplitude's ultraviolet pole in the critical dimension of D = 11/2, the same dimension as for N = 4 super-Yang-Mills theory. Strikingly, exactly the same combination of vacuum integrals (after simplification) describes the ultraviolet divergence of N = 8 supergravity as the subleading-in-1/N{sub c}{sup 2} single-trace divergence in N = 4 super-Yang-Mills theory.

Chronological changes in the eighth cranial nerve compound action potential (CAP) in experimental endolymphatic hydrops: the effects of altering the polarity of click sounds.

Science.gov (United States)

Morizono, Tetsuo; Kondo, Tsuyoshi; Yamano, Takafumi; Miyagi, Morimichi; Shiraishi, Kimio

2009-02-01

Using a guinea pig model of experimental endolymphatic hydrops, click sounds of altered polarity showed different latencies and amplitudes in hydropic compared with normal cochleae. Latency changes appeared as early as 1 week after endolymphatic obstruction. This method can help diagnose endolymphatic hydrops. The goal of the study was to develop an objective electrophysiological diagnosis of endolymphatic hydrops. Endolymphatic hydrops were created surgically in guinea pigs. The latency and the amplitude of the eighth cranial nerve compound action potential (CAP) for click sounds of altered polarity were measured up to 8 weeks after the surgery. At early stages after surgery, the latency for condensation clicks became longer, and at later stages the latencies for both condensation and rarefaction became longer. The discrepancy in the latencies for rarefaction and condensation click sounds (rarefaction minus condensation) became larger by the first week after surgery, but no further discrepancy occurred thereafter. Compared with latency changes, amplitude changes in the CAP were rapid and progressive following surgery, suggesting ongoing damage to hair cells.

Amplitude damping of vortex modes

CSIR Research Space (South Africa)

Dudley, Angela L

2010-09-01

Full Text Available An interferometer, mimicking an amplitude damping channel for vortex modes, is presented. Experimentally the action of the channel is in good agreement with that predicted theoretically. Since we can characterize the action of the channel on orbital...

Singularities of elastic scattering amplitude by long-range potentials

International Nuclear Information System (INIS)

Kvitsinsky, A.A.; Komarov, I.V.; Merkuriev, S.P.

1982-01-01

The angular peculiarities and the zero energy singularities of the elastic scattering amplitude by a long-range potential are described. The singularities of the elastic (2 → 2) scattering amplitude for a system of three Coulomb particles are considered [ru

Factorization of the six-particle multi-Regge amplitude

International Nuclear Information System (INIS)

Moen, I.O.

1975-01-01

It is shown that factorization of the multi-Regge contribution to the six-particle amplitude follows from the complex-helicity-plane structure, the Steinmann relations, and extended unitarity. The six-particle multi-Regge amplitude also satisfies some new discontinuity relations which are interpreted as resulting from the interplay of singularities required by the Gram-determinant constraint in four-dimensional space-time

Einstein-Yang-Mills from pure Yang-Mills amplitudes

Energy Technology Data Exchange (ETDEWEB)

Nandan, Dhritiman; Plefka, Jan [Institut für Physik and IRIS Adlershof, Humboldt-Universität zu Berlin,Zum Großen Windkanal 6, D-12489 Berlin (Germany); Schlotterer, Oliver [Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut,Am Mühlenberg 1, D-14476 Potsdam (Germany); Wen, Congkao [I.N.F.N. Sezione di Roma Tor Vergata,Via della Ricerca Scientifica, 00133 Roma (Italy)

2016-10-14

We present new relations for scattering amplitudes of color ordered gluons and gravitons in Einstein-Yang-Mills theory. Tree-level amplitudes of arbitrary multiplicities and polarizations involving up to three gravitons and up to two color traces are reduced to partial amplitudes of pure Yang-Mills theory. In fact, the double-trace identities apply to Einstein-Yang-Mills extended by a dilaton and a B-field. Our results generalize recent work of Stieberger and Taylor for the single graviton case with a single color trace. As the derivation is made in the dimension-agnostic Cachazo-He-Yuan formalism, our results are valid for external bosons in any number of spacetime dimensions. Moreover, they generalize to the superamplitudes in theories with 16 supercharges.

Amplitude Models for Discrimination and Yield Estimation

Energy Technology Data Exchange (ETDEWEB)

Phillips, William Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-09-01

This seminar presentation describes amplitude models and yield estimations that look at the data in order to inform legislation. The following points were brought forth in the summary: global models that will predict three-component amplitudes (R-T-Z) were produced; Q models match regional geology; corrected source spectra can be used for discrimination and yield estimation; three-component data increase coverage and reduce scatter in source spectral estimates; three-component efforts must include distance-dependent effects; a community effort on instrument calibration is needed.

Singularity Structure of Maximally Supersymmetric Scattering Amplitudes

DEFF Research Database (Denmark)

Arkani-Hamed, Nima; Bourjaily, Jacob L.; Cachazo, Freddy

2014-01-01

We present evidence that loop amplitudes in maximally supersymmetric (N=4) Yang-Mills theory (SYM) beyond the planar limit share some of the remarkable structures of the planar theory. In particular, we show that through two loops, the four-particle amplitude in full N=4 SYM has only logarithmic ...... singularities and is free of any poles at infinity—properties closely related to uniform transcendentality and the UV finiteness of the theory. We also briefly comment on implications for maximal (N=8) supergravity theory (SUGRA)....

Effect of Stress Amplitude on the Damping of Recycled Aggregate Concrete.

Science.gov (United States)

Liang, Chaofeng; Liu, Tiejun; Xiao, Jianzhuang; Zou, Dujian; Yang, Qiuwei

2015-08-14

Damping characterizes the energy dissipation capacity of materials and structures, and it is affected by several external factors such as vibrating frequency, stress history, temperature, and stress amplitude. This study investigates the relationship between the damping and the stress amplitude of environment-friendly recycled aggregate concrete (RAC). First, a function model of a member's loss factor and stress amplitude was derived based on Lazan's damping-stress function. Then, the influence of stress amplitude on the loss tangent of RAC was experimentally investigated. Finally, parameters used to determine the newly derived function were obtained by numerical fitting. It is shown that the member's loss factor is affected not only by the stress amplitude but also by factors such as the cross section shapes, boundary conditions, load types, and loading positions. The loss tangent of RAC increases with the stress amplitude, even at low stress amplitude. The damping energy exponent of RAC is not identically equal to 2.0, indicating that the damping is nonlinear. It is also found that the energy dissipation capacity of RAC is superior to that of natural aggregate concrete (NAC), and the energy dissipation capacity can be further improved by adding modified admixtures.

On the Construction of Scattering Amplitudes for Spinning Massless Particles

CERN Document Server

Berends, F A

1997-01-01

In this paper the general form of scattering amplitudes for massless particles with equal spins s ($s s \\to s s$) or unequal spins ($s_a s_b \\to s_a s_b$) are derived. The imposed conditions are that the amplitudes should have the lowest possible dimension, have propagators of dimension $m^{-2}$, and obey gauge invariance. It is shown that the number of momenta required for amplitudes involving particles with s > 2 is higher than the number implied by 3-vertices for higher spin particles derived in the literature. Therefore, the dimension of the coupling constants following from the latter 3-vertices has a smaller power of an inverse mass than our results imply. Consequently, the 3-vertices in the literature cannot be the first interaction terms of a gauge-invariant theory. When no spins s > 2 are present in the process the known QCD, QED or (super) gravity amplitudes are obtained from the above general amplitudes.

Scruncher phase and amplitude control

International Nuclear Information System (INIS)

DeHaven, R.A.; Morris, C.L.; Johnson, R.; Davis, J.; O'Donnell, J.M.

1992-01-01

The analog controller for phase and amplitude control of a 402.5 MHz super conducting cavity is described in this paper. The cavity is a single cell with niobium explosively bonded to a copper cavity. It is used as an energy compressor for pions at the Clinton P. Anderson Meson Physics Facility (LAMPF). The controller maintains cavity frequency to within 4 degrees in phase of the LAMPF beam frequency. Field amplitude is maintained to within 2 percent. This control is accomplished at critical coupling (Q load of 1 x 10 9 ) with the use of only a 30 watt rf amplifier for accelerating fields of 6 MV/m. The design includes the use of piezoelectric crystals for fast resonance control. Three types of control, self excited, VCO, and a reference frequency driven, were tried on this cavity and we present a comparison of their performance. (Author) 4 figs., ref

SCRUNCHER phase and amplitude control

International Nuclear Information System (INIS)

DeHaven, R.A.; Morris, C.L.; Johnson, R.; Davis, J.; O'Donnell, J.M.

1992-01-01

The analog controller for phase and amplitude control of a 402.5 MHz super conducting cavity is described in this paper. The cavity is a single cell with niobium explosively bonded to a copper cavity. It is used as an energy compressor for pions at the Clinton P. Anderson Meson Physics Facility (LAMPF). The controller maintains cavity frequency to within 4 degrees in phase of the LAMPF beam frequency. Field amplitude is maintained to within 2 percent. This control is accomplished at critical coupling (Q loaded of 1 x 10 9 ) with the use of only a 30 watt rf amplifier for accelerating fields of 6 MV/m. The design includes the use of piezoelectric crystals for fast resonance control. Three types of control, self excited VCO, and a reference frequency driven, were tried on this cavity and we present a comparison of their performance

Accommodative Amplitude in School-Age Children

Directory of Open Access Journals (Sweden)

Ikaunieks Gatis

2017-10-01

Full Text Available In children, intensive near-work affects the accommodation system of the eye. Younger children, due to anatomical parameters, read at smaller distance than older children and we can expect that the accommodation system of younger can be affected more than that of older children. We wanted to test this hypothesis. Some authors showed that the norms of amplitude of accommodation (AA developed by Hofstetter (1950 not always could be applied for children. We also wanted to verify these results. A total of 106 (age 7-15 children participated in the study. Distance visual acuity was measured for all children and only data of children with good visual acuity 1.0 or more (dec. units were analysed (73 children. Accommodative amplitude was measured before and after lessons using subjective push-up technique (with RAF Near Point Ruler. The results showed that the amplitude of accommodation reduced significantly (p < 0.05 during the day and decrease of AA was similar in different age groups (about ~0.70 D. Additional measurements are needed to verify that the observed changes in AA were associated with fatigue effect. The results showed lower accommodation values compared to average values calculated according to the Hofstetter equation (p < 0.05.

Double logarithmic asymptotics of quark amplitudes with flavour exchange

International Nuclear Information System (INIS)

Kirschner, R.

1982-01-01

Results on the quark scattering and annihilation amplitudes in the Regge region are presented. The perturbative contribution to those amplitudes in the double logarithmic approximation are calculated. In the calculations a method based on dispersion relations and gauge invariance is used. (M.F.W.)

Hilbert-Schmidt expansion for the nucleon-deuteron scattering amplitude

International Nuclear Information System (INIS)

Moeller, K.; Narodetskii, I.M.

1983-01-01

The Hilbert-Schmidt method is used to sum the divergent iterative series for the partial amplitudes of nucleon-deuteron scattering in the energy region above the deuteron breakup threshold. It is observed that the Hilbert-Schmidt series for the partial amplitudes themselves diverges, which is due to the closeness of the logarithmic singularities. But if the first iterations in the series for multiple scattering are subtracted from the amplitude, the Hilbert-Schmidt series for the remainder converges rapidly. The final answer obtained in the present paper is in excellent agreement with the results obtained in exact calculations

Amplitude Modulation in the δ Sct star KIC 7106205

Directory of Open Access Journals (Sweden)

Bowman Dominic. M.

2015-01-01

Full Text Available The δ Sct star KIC 7106205 showed amplitude modulation in a single p mode, whilst all other p and g modes remained stable in amplitude and phase over 1470 d of the Kepler dataset. The data were divided into 30 time bins of equal length and a series of consecutive Fourier transforms was calculated. A fixed frequency, calculated from a least-squares fit of all data, allowed amplitude and phase for every mode in each time bin to be tracked. The missing p mode energy was not transferred to any other visible modes.

Separation of musical instruments based on amplitude and frequency comodulation

Science.gov (United States)

Jacobson, Barry D.; Cauwenberghs, Gert; Quatieri, Thomas F.

2002-05-01

In previous work, amplitude comodulation was investigated as a basis for monaural source separation. Amplitude comodulation refers to similarities in amplitude envelopes of individual spectral components emitted by particular types of sources. In many types of musical instruments, amplitudes of all resonant modes rise/fall, and start/stop together during the course of normal playing. We found that under certain well-defined conditions, a mixture of constant frequency, amplitude comodulated sources can unambiguously be decomposed into its constituents on the basis of these similarities. In this work, system performance was improved by relaxing the constant frequency requirement. String instruments, for example, which are normally played with vibrato, are both amplitude and frequency comodulated sources, and could not be properly tracked under the constant frequency assumption upon which our original algorithm was based. Frequency comodulation refers to similarities in frequency variations of individual harmonics emitted by these types of sources. The analytical difficulty is in defining a representation of the source which properly tracks frequency varying components. A simple, fixed filter bank can only track an individual spectral component for the duration in which it is within the passband of one of the filters. Alternatives are therefore explored which are amenable to real-time implementation.

Distribution amplitudes of vector mesons

Energy Technology Data Exchange (ETDEWEB)

Braun, V.M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Broemmel, D. [Deutsches Elektronen-Synchrotron, Hamburg (Germany); Goeckeler, M. [Regensburg Univ. (DE). Inst. fuer Theoretische Physik] (and others)

2007-11-15

Results are presented for the lowest moment of the distribution amplitude for the K{sup *} vector meson. Both longitudinal and transverse moments are investigated. We use two flavours of O(a) improved Wilson fermions, together with a non-perturbative renormalisation of the matrix element. (orig.)

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity

Directory of Open Access Journals (Sweden)

Anna M. Klawonn

2018-04-01

Full Text Available The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs in dopamine D1 receptor (D1R expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT, during various reward-enforced behaviors and in a “waiting”-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs in the 5-choice-serial-reaction-time-task (5CSRTT than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG expression (cFos and FosB induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.

Science.gov (United States)

Klawonn, Anna M; Wilhelms, Daniel B; Lindström, Sarah H; Singh, Anand Kumar; Jaarola, Maarit; Wess, Jürgen; Fritz, Michael; Engblom, David

2018-01-01

The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression ( cFos and FosB ) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

Explosion Amplitude Reduction due to Fractures in Water-Saturated and Dry Granite

Science.gov (United States)

Stroujkova, A. F.; Leidig, M.; Bonner, J. L.

2013-12-01

Empirical observations made at the Semipalatinsk Test Site suggest that nuclear tests in the fracture zones left by previous explosions ('repeat shots') show reduced seismic amplitudes compared to the nuclear tests in virgin rocks. Likely mechanisms for the amplitude reduction in the repeat shots include increased porosity and reduced strength and elastic moduli, leading to pore closing and frictional sliding. Presence of pore water significantly decreases rock compressibility and strength, thus affecting seismic amplitudes. A series of explosion experiments were conducted in order to define the physical mechanism responsible for the amplitude reduction and to quantify the degree of the amplitude reduction in fracture zones of previously detonated explosions. Explosions in water-saturated granite were conducted in central New Hampshire in 2011 and 2012. Additional explosions in dry granite were detonated in Barre, VT in 2013. The amplitude reduction is different between dry and water-saturated crystalline rocks. Significant reduction in seismic amplitudes (by a factor of 2-3) in water-saturated rocks was achieved only when the repeat shot was detonated in the extensive damage zone created by a significantly larger (by a factor of 5) explosion. In case where the first and the second explosions were similar in yield, the amplitude reduction was relatively modest (5-20%). In dry rocks the amplitude reduction reached a factor of 2 even in less extensive damage zones. In addition there are differences in frequency dependence of the spectral amplitude ratios between explosions in dry and water-saturated rocks. Thus the amplitude reduction is sensitive to the extent of the damage zone as well as the pore water content.

Basic perceptual changes that alter meaning and neural correlates of recognition memory.

Science.gov (United States)

Gao, Chuanji; Hermiller, Molly S; Voss, Joel L; Guo, Chunyan

2015-01-01

It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color) on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not). Abstract visual shapes ("squiggles") were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential (ERP) correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400), implying that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition). Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates of memory

Weak decay amplitudes in large N/sub c/ QCD

International Nuclear Information System (INIS)

Bardeen, W.A.

1988-10-01

A systematic analysis of nonleptonic decay amplitudes is presented using the large N/sub c/ expansion of quantum chromodynamics. In the K-meson system, this analysis is applied to the calculation of the weak decay amplitudes, weak mixing and CP violation. 10 refs., 5 figs., 2 tabs

Sex-related differences in the muscarinic acetylcholinergic receptor in the healthy human brain. A positron emission tomography study

International Nuclear Information System (INIS)

Yoshida, Tsuyoshi; Kuwabara, Yasuo; Sasaki, Masayuki; Ichimiya, Atsushi; Takita, Masashi; Ogomori, Koji; Masuda, Kouji; Fukumura, Toshimitsu; Ichiya, Yuichi

2000-01-01

We evaluated the sex-related differences in the decline of the cerebral muscarinic acetylcholinergic receptor (mACh-R) due to aging by using 11 C-N-methyl-4-piperidyl benzilate ( 11 C-NMPB) and positron emission tomography (PET). The subjects consisted of 37 (20 males and 17 females) healthy volunteers. The 11 C-NMPB uptake was evaluated by the ratio method (regional 11 C-NMPB uptake/Cerebellar 11 C-NMPB uptake; rNMPB ratio). The correlation between sex, aging, and the rNMPB ratio in normal aging was evaluated by a multiple regression analysis. The rNMPB ratio was higher in females than in males throughout the entire cerebral region (p<0.01-p<0.0001) and the rNMPB ratio might thus possibly decline with age more rapidly in females. Our study therefore revealed the existence of sex-related differences in the cerebral mACh-R. (author)

Scalar-field amplitudes in black-hole evaporation

International Nuclear Information System (INIS)

Farley, A.N.St.J.; D'Eath, P.D.

2004-01-01

We consider the quantum-mechanical decay of a Schwarzschild-like black hole into almost-flat space and weak radiation at a very late time. That is, we are concerned with evaluating quantum amplitudes (not just probabilities) for transitions from initial to final states. In this quantum description, no information is lost because of the black hole. The Lagrangian is taken, in the first instance, to consist of the simplest locally supersymmetric generalization of Einstein gravity and a massless scalar field. The quantum amplitude to go from given initial to final bosonic data in a slightly complexified time-interval T=τexp(-iθ) at infinity may be approximated by the form constxexp(-I), where I is the (complex) Euclidean action of the classical solution filling in between the boundary data. Additionally, in a pure supergravity theory, the amplitude constxexp(-I) is exact. Suppose that Dirichlet boundary data for gravity and the scalar field are posed on an initial spacelike hypersurface extending to spatial infinity, just prior to collapse, and on a corresponding final spacelike surface, sufficiently far to the future of the initial surface to catch all the Hawking radiation. Only in an averaged sense will this radiation have an approximately spherically-symmetric distribution. If the time-interval T had been taken to be exactly real, then the resulting 'hyperbolic Dirichlet boundary-value problem' would, as is well known, not be well posed. Provided instead ('Euclidean strategy') that one takes T complex, as above (0<θ=<π/2), one expects that the field equations become strongly elliptic, and that there exists a unique solution to the classical boundary-value problem. Within this context, by expanding the bosonic part of the action to quadratic order in perturbations about the classical solution, one obtains the quantum amplitude for weak-field final configurations, up to normalization. Such amplitudes are here calculated for weak final scalar fields

RECOLA2: REcursive Computation of One-Loop Amplitudes 2

Science.gov (United States)

Denner, Ansgar; Lang, Jean-Nicolas; Uccirati, Sandro

2018-03-01

We present the Fortran95 program RECOLA2 for the perturbative computation of next-to-leading-order transition amplitudes in the Standard Model of particle physics and extended Higgs sectors. New theories are implemented via model files in the 't Hooft-Feynman gauge in the conventional formulation of quantum field theory and in the Background-Field method. The present version includes model files for Two-Higgs-Doublet Model and the Higgs-Singlet Extension of the Standard Model. We support standard renormalization schemes for the Standard Model as well as many commonly used renormalization schemes in extended Higgs sectors. Within these models the computation of next-to-leading-order polarized amplitudes and squared amplitudes, optionally summed over spin and colour, is fully automated for any process. RECOLA2 allows the computation of colour- and spin-correlated leading-order squared amplitudes that are needed in the dipole subtraction formalism. RECOLA2 is publicly available for download at http://recola.hepforge.org.

Amplitude Variations in Pulsating Red Giants. II. Some Systematics

Science.gov (United States)

Percy, J. R.; Laing, J.

2017-12-01

In order to extend our previous studies of the unexplained phenomenon of cyclic amplitude variations in pulsating red giants, we have used the AAVSO time-series analysis package vstar to analyze long-term AAVSO visual observations of 50 such stars, mostly Mira stars. The relative amount of the variation, typically a factor of 1.5, and the time scale of the variation, typically 20-35 pulsation periods, are not significantly different in longer-period, shorter-period, and carbon stars in our sample, and they also occur in stars whose period is changing secularly, perhaps due to a thermal pulse. The time scale of the variations is similar to that in smaller-amplitude SR variables, but the relative amount of the variation appears to be larger in smaller-amplitude stars, and is therefore more conspicuous. The cause of the amplitude variations remains unclear, though they may be due to rotational modulation of a star whose pulsating surface is dominated by the effects of large convective cells.

Spinal cord regeneration by modulating bone marrow with neurotransmitters and Citicholine: Analysis at micromolecular level.

Science.gov (United States)

Paulose, Cheramadathukudiyil Skaria; John, Ponnezhathu Sebastian; Chinthu, Romeo; Akhilraj, Puthenveetil Raju; Anju, Thoppil Raveendran

2017-04-01

Spinal cord injury results in disruption of brain-spinal cord fibre connectivity, leading to progressive tissue damage at the site of injury and resultant paralysis of varying degrees. The current study investigated the role of autologous bone marrow modulated with neurotransmitters and neurotransmitter stimulating agent, Citicholine, in spinal cord of spinal cord injured rats. Radioreceptor assay using [3H] ligand was carried out to quantify muscarinic receptor. Gene expression studies were done using Real Time PCR analysis. Scatchard analysis of muscarinic M1 receptor showed significantly decreased B max (p neurotransmitters combination along with bone marrow or Citicholine with bone marrow can reverse the muscarinic receptor alterations in the spinal cord of spinal cord injured rats, which is a promising step towards a better therapeutic intervention for spinal cord injury because of the positive role of cholinergic system in regulation of both locomotor activity and synaptic plasticity. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.