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https://www.readbyqxmd.com/read/29912862/stochastic-shielding-and-edge-importance-for-markov-chains-with-timescale-separation
#1
Deena R Schmidt, Roberto F Galán, Peter J Thomas
Nerve cells produce electrical impulses ("spikes") through the coordinated opening and closing of ion channels. Markov processes with voltage-dependent transition rates capture the stochasticity of spike generation at the cost of complex, time-consuming simulations. Schmandt and Galán introduced a novel method, based on the stochastic shielding approximation, as a fast, accurate method for generating approximate sample paths with excellent first and second moment agreement to exact stochastic simulations...
June 18, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29912798/phase-iib-trial-of-an-%C3%AE-7-nicotinic-receptor-partial-agonist-with-and-without-nicotine-patch-for-withdrawal-associated-cognitive-deficits-and-tobacco-abstinence
#2
Randi Melissa Schuster, Gladys N Pachas, Luke Stoeckel, Corinne Cather, Mireya Nadal, David Mischoulon, David A Schoenfeld, Haiyue Zhang, Christine Ulysse, Elisabeth B Dodds, Sara Sobolewski, Vicenta Hudziak, Ailish Hanly, Maurizio Fava, A Eden Evins
PURPOSE/BACKGROUND: The objective of this study was to determine whether a novel α7 nicotinic acetylcholine receptor partial agonist improves cognition during nicotine withdrawal and improves abstinence rates. To do so, the effect of the α7 nicotinic acetylcholine receptor partial agonist, encenicline, on cognition and abstinence was evaluated when given as monotherapy and when combined with transdermal nicotine patch (nicotine replacement therapy [NRT]). METHODS: Adult daily smokers, n = 160, who were motivated to quit smoking completed cognitive testing at satiated baseline and after overnight abstinence and then were randomized to receive a 12-week trial of encenicline 1 mg twice daily or identical placebo the day of the overnight abstinent cognitive testing...
June 14, 2018: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29910731/alpha6-containing-nicotinic-acetylcholine-receptors-mediate-nicotine-induced-structural-plasticity-in-mouse-and-human-ipsc-derived-dopaminergic-neurons
#3
Ginetta Collo, Laura Cavalleri, Michele Zoli, Uwe Maskos, Emiliangelo Ratti, Emilio Merlo Pich
Midbrain dopamine (DA) neurons are considered a critical substrate for the reinforcing and sensitizing effects of nicotine and tobacco dependence. While the role of the α4 and β2 subunit containing nicotinic acetylcholine receptors (α4β2∗ nAChRs) in mediating nicotine effects on DA release and DA neuron activity has been widely explored, less information is available on their role in the morphological adaptation of the DA system to nicotine, eventually leading to dysfunctional behaviors observed in nicotine dependence...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29910685/activation-of-central-alpha-7-nicotinic-acetylcholine-receptor-reverses-suppressed-immune-function-of-t-lymphocytes-and-protects-against-sepsis-lethality
#4
Chao Ren, Xiu-Hua Li, Shi-Bin Wang, Li-Xue Wang, Ning Dong, Yao Wu, Yong-Ming Yao
Sepsis remains the leading cause of high mortality and huge financial burden in intensive care units (ICU), but with scarce effective treatments due to refractory multiple organ dysfunction and persistent immunosuppression. Treatments that aim at modulating immune function and attenuating multiple organ injury will certainly benefit septic cases. Alpha 7 nicotinic acetylcholine receptor (α7nAchR) has been reported with potent immunomodulatory properties in various diseases as the essential mediator of the cholinergic anti-inflammatory pathway (CAP)...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29908200/differential-effects-of-withdrawal-from-intermittent-and-continuous-nicotine-exposure-on-reward-deficit-and-somatic-aspects-of-nicotine-withdrawal-and-expression-of-%C3%AE-4%C3%AE-2-nachrs-in-wistar-male-rats
#5
Svetlana Semenova, Xinchun Jin, Tristan D McClure-Begley, Matthew Philip Tadman, Michael J Marks, Athina Markou
BACKGROUND: Chronic nicotine exposure produces neuroadaptations in brain reward systems and α4β2 nicotinic acetylcholine receptors (nAChRs) in the corticolimbic brain areas. We previously demonstrated opposite effects of nicotine exposure delivered by self-administration or pumps on brain reward thresholds that can be attributed to the different temporal pattern and contingency of nicotine exposure. We investigated the effects of these two factors on reward thresholds and somatic signs during nicotine withdrawal, and on nAChRs binding in corticolimbic brain areas...
June 13, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29902578/the-impact-of-the-effectiveness-of-gata3-as-a-prognostic-factor-in-breast-cancer
#6
Fararjeh-Salah Abdul Fattah, Shih-Hsin Tu, Li-Ching Chen, Yun-Ru Liu, Yen-Kuang Lin, Hang-Lung Chang, Hui-Wen Chang, Chih-Hsiung Wu, Wendy-Hwang Verslues, Yuan-Soon Ho
The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semi-quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR), quantitative real-time PCR carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n=25)...
June 11, 2018: Human Pathology
https://www.readbyqxmd.com/read/29901817/nicotine-treatment-ameliorates-dss-induced-colitis-by-suppressing-madcam-1-expression-and-leukocyte-recruitment
#7
Koji Maruta, Chikako Watanabe, Hideaki Hozumi, Chie Kurihara, Hirotaka Furuhashi, Takeshi Takajo, Yoshikiyo Okada, Kazuhiko Shirakabe, Masaaki Higashiyama, Shunsuke Komoto, Kengo Tomita, Shigeaki Nagao, Toshiaki Ishizuka, Soichiro Miura, Ryota Hokari
The enhanced recruitment of leukocytes to the inflamed colon is a key feature of ulcerative colitis (UC). The gut-specific adhesion molecules involved in leukocyte recruitment have emerged as recent therapeutic targets. Nicotine absorbed from smoking has been reported to work protectively in UC patients. Our hypothesis is that nicotine may suppress the aberrant leukocyte recruitment and colonic inflammation via the suppression of the overexpressed gut-specific adhesion molecules in the inflamed colon. To test this hypothesis, the severity of colitis and the degree of leukocyte recruitment induced by gut-specific adhesion molecules were assessed in dextran sulfate sodium (DSS) colitis mice (C57BL/6J mice treated with 3% DSS) with or without nicotine treatment...
June 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29901389/3-4-dihydroxyphenylethanol-assuages-cognitive-impulsivity-in-alzheimer-s-disease-by-attuning-hpa-axis-via-differential-crosstalk-of-%C3%AE-7-nachr-with-microrna-124-and-hdac6
#8
ArunSundar MohanaSundaram, Thukani Sathanantham Shanmugarajan, Velayutham Ravichandiran
Cognitive impulsivity, a form of suboptimal cost-benefit decision making is an illustrious attribute of an array of neurodegenerative diseases including Alzheimer's Disease (AD). In this study, delay discounting paradigm was used to assess the effect of 3,4-dihydroxyphenylethanol (DOPET) on cognitive impulsivity-in an oA42i (oligomeric amyloid β1-42 plus ibotenic acid) induced AD mouse model-using a non-spatial T-maze task. The results depicted that oA42i administration elevated cognitive impulsivity, whereas DOPET treatment attenuated the impulsive behavior and matched the choice of the sham-operated controls...
June 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29899286/neuronal-nicotinic-acetylcholine-receptor-modulators-from-cone-snails
#9
REVIEW
Nikita Abraham, Richard J Lewis
Marine cone snails are a large family of gastropods that have evolved highly potent venoms for predation and defense. The cone snail venom has exceptional molecular diversity in neuropharmacologically active compounds, targeting a range of receptors, ion channels, and transporters. These conotoxins have helped to dissect the structure and function of many of these therapeutically significant targets in the central and peripheral nervous systems, as well as unravelling the complex cellular mechanisms modulated by these receptors and ion channels...
June 13, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29898654/developmental-nicotine-exposure-affects-larval-brain-size-and-the-adult-dopaminergic-system-of-drosophila-melanogaster
#10
Melanie Morris, Ariel Shaw, Madison Lambert, Haley Halperin Perry, Eve Lowenstein, David Valenzuela, Norma Andrea Velazquez-Ulloa
BACKGROUND: Pregnant women may be exposed to nicotine if they smoke or use tobacco products, nicotine replacement therapy, or via e-cigarettes. Prenatal nicotine exposure has been shown to have deleterious effects on the nervous system in mammals including changes in brain size and in the dopaminergic system. The genetic and molecular mechanisms for these changes are not well understood. A Drosophila melanogaster model for these effects of nicotine exposure could contribute to faster identification of genes and molecular pathways underlying these effects...
June 14, 2018: BMC Developmental Biology
https://www.readbyqxmd.com/read/29894316/high-throughput-screening-in-larval-zebrafish-identifies-novel-potent-sedative-hypnotics
#11
Xiaoxuan Yang, Youssef Jounaidi, Jennifer B Dai, Francisco Marte-Oquendo, Elizabeth S Halpin, Lauren E Brown, Richard Trilles, Wenqing Xu, Renee Daigle, Buwei Yu, Scott E Schaus, John A Porco, Stuart A Forman
BACKGROUND: Many general anesthetics were discovered empirically, but primary screens to find new sedative-hypnotics in drug libraries have not used animals, limiting the types of drugs discovered. The authors hypothesized that a sedative-hypnotic screening approach using zebrafish larvae responses to sensory stimuli would perform comparably to standard assays, and efficiently identify new active compounds. METHODS: The authors developed a binary outcome photomotor response assay for zebrafish larvae using a computerized system that tracked individual motions of up to 96 animals simultaneously...
June 12, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29891379/nicotinic-acetylcholine-receptor-subunit-%C3%AE-6-associated-with-spinosad-resistance-in-rhyzopertha-dominica-coleoptera-bostrichidae
#12
Hang-Tang Wang, Cheng-Lung Tsai, Mei-Er Chen
The lesser grain borer, Rhyzopertha dominica, which is a primary pest of stored products, breaks up whole grains and makes them susceptible to secondary infestation by other pests. Insecticide application is the main control measure against this borer. A resistant strain of R. dominica against the insecticide, spinosad, was selected in the laboratory. The full-length cDNA of the target site of spinosad, nicotinic acetylcholine receptor subunit α6, from R. dominica (Rdα6) was cloned and analyzed using reverse transcription PCR and rapid amplification of cDNA ends...
June 2018: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29888694/sex-difference-in-counts-of-%C3%AE-4-and-%C3%AE-7-nicotinic-acetylcholine-receptors-in-the-nasal-polyps-of-adults-with-or-without-exposure-to-tobacco-smoke
#13
B B Montaño-Velázquez, D A Lara-Sánchez, A Orozco-Sánchez, F J García-Vázquez, M R Mora-Campos, K Jáuregui-Renaud
OBJECTIVE: To assess counts of α4 and α7 nicotinic acetylcholine receptors in nasal polyps of adults with or without long-term exposure to cigarette tobacco smoke. METHODS: Twenty-two patients with and 22 patients without exposure to cigarette tobacco smoke participated in the study. After endoscopic polypectomy, the fragments of the nasal polyps were analysed by immunohistochemistry. RESULTS: Compared to patients with no exposure, patients with exposure showed higher counts of α4 and α7 nicotinic acetylcholine receptors (t-test, p 0...
June 11, 2018: Journal of Laryngology and Otology
https://www.readbyqxmd.com/read/29885447/electroacupuncture-prevents-cognitive-impairment-induced-by-lipopolysaccharide-via-inhibition-of-oxidative-stress-and-neuroinflammation
#14
Yao-Guo Han, Xiong Qin, Tao Zhang, Ming Lei, Fang-Yuan Sun, Jing-Jing Sun, Wei-Fang Yuan
Oxidative stress and neuroinflammation play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced cognitive impairment. This study aims to observe the effect of electroacupuncture (EA) on the cognitive function in LPS-induced mice, and its regulation on hippocampal α7 nicotinic acetylcholine receptors (α7nAChR), oxidative and proinflammatory factors. Adult male C57BL/6 nice were used to establish animal model of LPS-induced cognitive impairment, and were randomly divided into three groups (n = 16): control group, model group (LPS: 5 mg/kg), and EA group...
June 6, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29881944/-e-nicotinaldehyde-o-cinnamyloxime-a-nicotine-analog-attenuates-neuronal-cells-death-against-rotenone-induced-neurotoxicity
#15
Juan Camilo Jurado-Coronel, Alix E Loaiza, John E Díaz, Ricardo Cabezas, Ghulam Md Ashraf, Amirhossein Sahebkar, Valentina Echeverria, Janneth González, George E Barreto
Parkinson's disease (PD) is a neurodegenerative pathology characterized by resting tremor, rigidity, bradykinesia, and loss of dopamine-producing neurons in the pars compacta of the substantia nigra in the central nervous system (CNS) that result in dopamine depletion in the striatum. Oxidative stress has been documented as a key pathological mechanism for PD. Epidemiological studies have shown that smokers have a lower incidence of PD. In this aspect, different studies have shown that nicotine, a chemical compound found in cigarette, is capable of exerting beneficial effects in PD patients, but it can hardly be used as a therapeutic agent because of its inherent toxicity...
June 7, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29879409/importance-of-kynurenine-3-monooxygenase-for-spontaneous-firing-and-pharmacological-responses-of-midbrain-dopamine-neurons-relevance-for-schizophrenia
#16
Maximilian Tufvesson-Alm, Lilly Schwieler, Robert Schwarcz, Michel Goiny, Sophie Erhardt, Göran Engberg
Kynurenine 3-monooxygenase (KMO) is an essential enzyme of the kynurenine pathway, converting kynurenine into 3-hydroxykynurenine. Inhibition of KMO increases kynurenine, resulting in elevated levels of kynurenic acid (KYNA), an endogenous N-methyl-D-aspartate and α*7-nicotinic receptor antagonist. The concentration of KYNA is elevated in the brain of patients with schizophrenia, possibly as a result of a reduced KMO activity.In the present study, using in vivo single cell recording techniques, we investigated the electrophysiological characteristics of ventral tegmental area dopamine (VTA DA) neurons and their response to antipsychotic drugs in a KMO knock-out (K/O) mouse model...
June 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29878346/nicotinic-acetylcholine-receptors
#17
EDITORIAL
Sue Wonnacott, Isabel Bermudez, Neil S Millar, Socrates J Tzartos
This themed section of the British Journal of Pharmacology is the product of a conference that focussed on nicotinic ACh receptors (nAChRs) that was held on the Greek island of Crete from 7 to 11 May 2017. 'Nicotinic acetylcholine receptors 2017' was the fourth in a series of triennial international meetings that have provided a regular forum for scientists working on all aspects of nAChRs to meet and to discuss new developments. In addition to many of the regular participants, each meeting has also attracted a new group of scientists working in a fast-moving area of research...
June 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29877026/the-binding-properties-of-cycloxaprid-on-insect-native-nachrs-partially-explain-the-low-cross-resistance-with-imidacloprid-in-nilaparvata-lugens
#18
Yixi Zhang, Xiaoyong Xu, Haibo Bao, Xusheng Shao, Zhong Li, Zewen Liu
BACKGROUND: Neonicotinoids, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) to control Nilaparvata lugens, a major rice insect pest. High imidacloprid resistance has been reported in N. lugens in laboratory and in fields. Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity against N. lugens and low cross-resistance in the imidacloprid resistant strains and field populations. RESULTS: Binding studies have demonstrated that imidacloprid had two binding sites with different affinities (Kd = 3...
June 6, 2018: Pest Management Science
https://www.readbyqxmd.com/read/29870540/cigarette-toxin-4-methylnitrosamino-1-3-pyridyl-1-butanone-nnk-induces-experimental-pancreatitis-through-%C3%AE-7-nicotinic-acetylcholine-receptors-nachrs-in-mice
#19
A A Alahmari, B Sreekumar, V Patel, M Ashat, M Alexandre, A K Uduman, E O Akinbiyi, A Ceplenski, C A Shugrue, T R Kolodecik, N Tashkandi, S W Messenger, G E Groblewski, F S Gorelick, E C Thrower
Clinical studies have shown that cigarette smoking is a dose-dependent and independent risk factor for acute pancreatitis. Cigarette smoke contains nicotine which can be converted to the potent receptor ligand and toxin, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Previously, we have shown that NNK induces premature activation of pancreatic zymogens in rats, an initiating event in pancreatitis, and this activation is prevented by pharmacologic inhibition of nicotinic acetylcholine receptors (nAChR)...
2018: PloS One
https://www.readbyqxmd.com/read/29866790/the-influence-of-nicotine-on-lung-tumor-growth-cancer-chemotherapy-and-chemotherapy-induced-peripheral-neuropathy
#20
S Lauren Kyte, David A Gewirtz
Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors (nAChRs), may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. While the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies...
June 4, 2018: Journal of Pharmacology and Experimental Therapeutics
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