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https://www.readbyqxmd.com/read/27903101/d-cycloserine-an-nmda-glutamate-receptor-glycine-site-partial-agonist-induces-acute-increases-in-brain-glutamate-plus-glutamine-and-gaba-comparable-to-ketamine
#1
Joshua T Kantrowitz, Matthew S Milak, Xiangling Mao, Dikoma C Shungu, J John Mann
No abstract text is available yet for this article.
December 1, 2016: American Journal of Psychiatry
https://www.readbyqxmd.com/read/27893705/gephyrin-binding-peptides-visualize-postsynaptic-sites-and-modulate-neurotransmission
#2
Hans Michael Maric, Torben Johann Hausrat, Franziska Neubert, Nils Ole Dalby, Sören Doose, Markus Sauer, Matthias Kneussel, Kristian Strømgaard
γ-Aminobutyric acid type A and glycine receptors are the major mediators of fast synaptic inhibition in the human central nervous system and are established drug targets. However, all drugs targeting these receptors bind to the extracellular ligand-binding domain of the receptors, which inherently is associated with perturbation of the basic physiological action. Here we pursue a fundamentally different approach, by instead targeting the intracellular receptor-gephyrin interaction. First, we defined the gephyrin peptide-binding consensus sequence, which facilitated the development of gephyrin super-binding peptides and later effective affinity probes for the isolation of native gephyrin...
November 28, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27892961/host-derived-extracellular-rna-promotes-adhesion-of-streptococcus-pneumoniae-to-endothelial-and-epithelial-cells
#3
Dariusz Zakrzewicz, Simone Bergmann, Miroslava Didiasova, Benedetto Daniele Giaimo, Tilman Borggrefe, Maren Mieth, Andreas C Hocke, Guenter Lochnit, Liliana Schaefer, Sven Hammerschmidt, Klaus T Preissner, Malgorzata Wygrecka
Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. The infection process involves bacterial cell surface receptors, which interact with host extracellular matrix components to facilitate colonization and dissemination of bacteria. Here, we investigated the role of host-derived extracellular RNA (eRNA) in the process of pneumococcal alveolar epithelial cell infection. Our study demonstrates that eRNA dose-dependently increased S. pneumoniae invasion of alveolar epithelial cells...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891689/deficit-in-acoustic-signal-in-noise-detection-in-glycine-receptor-%C3%AE-3-subunit-knockout-mice
#4
Konstantin Tziridis, Stefanie Buerbank, Volker Eulenburg, Julia Dlugaiczyk, Holger Schulze
Hearing is an essential sense for communication in animals and humans. Normal function of the cochlea of higher vertebrates relies on a fine-tuned interplay of afferent and efferent innervation of both inner and outer hair cells. Efferent inhibition is controlled via olivocochlear feedback loops, mediated mainly by acetylcholine, γ-aminobutyric acid (GABA) and glycine, and is one of the first sites affected by synapto- and neuropathy in the development of hearing loss. While the functions of acetylcholine, GABA, and other inhibitory transmitters within these feedback loops are at least partially understood, especially the function of glycine still remains elusive...
November 27, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27891197/the-oscillation-like-activity-in-bullfrog-on-off-retinal-ganglion-cell
#5
Xiao-Wei Qiu, Hai-Qing Gong, Pu-Ming Zhang, Pei-Ji Liang
Oscillatory activity of retinal ganglion cell (RGC) has been observed in various species. It was reported such oscillatory activity is raised within large neural network and involved in retinal information coding. In the present research, we found an oscillation-like activity in ON-OFF RGC of bullfrog retina, and studied the mechanisms underlying the ON and OFF activities respectively. Pharmacological experiments revealed that the oscillation-like activity patterns in both ON and OFF pathways were abolished by GABA receptor antagonists, indicating GABAergic inhibition is essential for generating them...
December 2016: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/27890711/the-endogenous-lipid-n-arachidonoyl-glycine-is-hypotensive-and-nitric-oxide-cgmp-dependent-vasorelaxant
#6
Yousuf M Al Suleimani, Ahmed S Al Mahruqi
N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1 mg/kg) decreased blood pressure by 69.4 ± 5.5% and reduced renal blood flow by 88 ± 12% and the effects were not sensitive to inhibition by O-1918 (3 mg/kg)...
November 24, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27866853/functional-annotation-of-ion-channel-structures-by-molecular-simulation
#7
Jemma L Trick, Sivapalan Chelvaniththilan, Gianni Klesse, Prafulla Aryal, E Jayne Wallace, Stephen J Tucker, Mark S P Sansom
Ion channels play key roles in cell membranes, and recent advances are yielding an increasing number of structures. However, their functional relevance is often unclear and better tools are required for their functional annotation. In sub-nanometer pores such as ion channels, hydrophobic gating has been shown to promote dewetting to produce a functionally closed (i.e., non-conductive) state. Using the serotonin receptor (5-HT3R) structure as an example, we demonstrate the use of molecular dynamics to aid the functional annotation of channel structures via simulation of the behavior of water within the pore...
November 8, 2016: Structure
https://www.readbyqxmd.com/read/27849094/synthetic-hydrogel-mimics-of-the-nuclear-pore-complex-display-selectivity-dependent-on-fg-repeat-concentration-and-electrostatics
#8
Alicia K Friedman, Lane A Baker
Synthetic hydrogels were utilized to explore influence of both charge and phenylalanine-glycine (FG) repeat concentration on translocation of select proteins. Hydrogels studied represent a biomimetic platform of the nuclear pore complex (NPC) found in eukaryotic cells. Polyacrylamide/phenylalanine-serine-phenylalanine-glycine (FSFG) peptide copolymers have previously demonstrated similar selectivity to native NPCs. Entry of a nuclear transport receptor (Impβ) into hydrogels was monitored with fluorescence microscopy and observed to be greater within gels that contained larger concentrations of FG peptide...
November 16, 2016: Soft Matter
https://www.readbyqxmd.com/read/27847466/glun2a-subunit-containing-nmda-receptors-are-the-preferential-neuronal-targets-of-homocysteine
#9
Dmitry A Sibarov, Polina A Abushik, Rashid Giniatullin, Sergei M Antonov
Homocysteine (HCY) is an endogenous redox active amino acid, best known as contributor to various neurodegenerative disorders. Although it is known that HCY can activate NMDA receptors (NMDARs), the mechanisms of its action on receptors composed of different NMDA receptor subunits remains almost unknown. In this study, using imaging and patch clamp technique in cultured cortical neurons and heterologous expression in HEK293T cells we tested the agonist activity of HCY on NMDARs composed of GluN1 and GluN2A subunits (GluN1/2A receptors) and GluN1 and GluN2B subunits (GluN1/2B receptors)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27836671/glycine-prevents-pressure-overload-induced-cardiac-hypertrophy-mediated-by-glycine-receptor
#10
Yan Lu, Xudong Zhu, Jinjie Li, Ru Fang, Zhuoyun Wang, Jing Zhang, Kexue Li, Xiaoyu Li, Hui Bai, Qing Yang, Jingjing Ben, Hanwen Zhang, Qi Chen
As a major amino acid, glycine has multiple functions in metabolism, growth, immunity, cytoprotection, and survival. The aim of this study was to determine the effects of glycine on pathologic cardiac hypertrophy and the mechanism underlying it. Pre-treatment with glycine significantly attenuated murine cardiac hypertrophy induced by transverse aortic constriction or by administration of angiotensin II (Ang II). This action was associated with a suppressive extracellular signal-regulated kinase 1/2 phosphorylation in myocardium...
November 9, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27835719/adjunctive-taurine-in-first-episode-psychosis-a-phase-2-double-blind-randomized-placebo-controlled-study
#11
Colin P O'Donnell, Kelly A Allott, Brendan P Murphy, Hok Pan Yuen, Tina-Marie Proffitt, Alicia Papas, Jennifer Moral, Tee Pham, Michaela K O'Regan, Christina Phassouliotis, Raelene Simpson, Patrick D McGorry
OBJECTIVE: Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-d-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder. METHODS: 121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009...
November 8, 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27830715/novel-agonist-bioisosteres-and-common-structure-activity-relationships-for-the-orphan-g-protein-coupled-receptor-gpr139
#12
Mohamed A Shehata, Anne C Nøhr, Delphine Lissa, Christoph Bisig, Vignir Isberg, Kirsten B Andersen, Kasper Harpsøe, Fredrik Björkling, Hans Bräuner-Osborne, David E Gloriam
GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and Parkinson's disease. The two aromatic amino acids L-Trp and L-Phe have been proposed as putative endogenous agonists, and three structurally related benzohydrazide, glycine benzamide, and benzotriazine surrogate agonist series have been published...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27826309/overexpression-of-nictaba-like-lectin-genes-from-glycine-max-confers-tolerance-toward-pseudomonas-syringae-infection-aphid-infestation-and-salt-stress-in-transgenic-arabidopsis-plants
#13
Sofie Van Holle, Guy Smagghe, Els J M Van Damme
Plants have evolved a sophisticated immune system that allows them to recognize invading pathogens by specialized receptors. Carbohydrate-binding proteins or lectins are part of this immune system and especially the lectins that reside in the nucleocytoplasmic compartment are known to be implicated in biotic and abiotic stress responses. The class of Nictaba-like lectins (NLL) groups all proteins with homology to the tobacco (Nicotiana tabacum) lectin, known as a stress-inducible lectin. Here we focus on two Nictaba homologs from soybean (Glycine max), referred to as GmNLL1 and GmNLL2...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27822554/farnesoid-x-receptor-signaling-shapes-the-gut-microbiota-and-controls-hepatic-lipid-metabolism
#14
Limin Zhang, Cen Xie, Robert G Nichols, Siu H J Chan, Changtao Jiang, Ruixin Hao, Philip B Smith, Jingwei Cai, Margaret N Simons, Emmanuel Hatzakis, Costas D Maranas, Frank J Gonzalez, Andrew D Patterson
The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism...
September 2016: MSystems
https://www.readbyqxmd.com/read/27819026/radiolabeled-cyclic-rgd-peptides-as-radiotracers-for-tumor-imaging
#15
REVIEW
Jiyun Shi, Fan Wang, Shuang Liu
The integrin family comprises 24 transmembrane receptors, each a heterodimeric combination of one of 18α and one of 8β subunits. Their main function is to integrate the cell adhesion and interaction with the extracellular microenvironment with the intracellular signaling and cytoskeletal rearrangement through transmitting signals across the cell membrane upon ligand binding. Integrin αvβ3 is a receptor for the extracellular matrix proteins containing arginine-glycine-aspartic (RGD) tripeptide sequence. The αvβ3 is generally expressed in low levels on the epithelial cells and mature endothelial cells, but it is highly expressed in many solid tumors...
2016: Biophysics Reports
https://www.readbyqxmd.com/read/27814910/humanin-ameliorates-diazepam-induced-memory-deficit-in-mice
#16
Minetaka Murakami, Masatoshi Nagahama, Takuma Maruyama, Takako Niikura
Humanin (HN) is an endogenous 24-residue peptide. A highly potent HN derivative, S14G-HN, which has a substitution of serine 14 to glycine, reduced amyloid burden and suppressed cognitive impairment in a mouse model of Alzheimer's disease. S14G-HN also suppressed amnesia induced by a muscarinic receptor antagonist in rodents. To understand the effects of HN on brain function, we tested the effect of S14G-HN on diazepam (DZP)-induced memory impairment and anxiety in mice using the object recognition test and zero-maze test, respectively...
October 29, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27812957/the-effects-of-verapamil-and-its-combinations-with-glutamate-and-glycine-on-cardiodynamics-coronary-flow-and-oxidative-stress-in-isolated-rat-heart
#17
Isidora Stojic, Ivan Srejovic, Vladimir Zivkovic, Nevena Jeremic, Marko Djuric, Ana Stevanovic, Tamara Milanovic, Dragan Djuric, Vladimir Jakovljevic
The role of N-methyl-D-aspartate receptor (NMDA-R) in heart is still unclear. For these ionotropic glutamate receptors is characteristic the necessity of both co-agonists, glutamate and glycine, for their activation, which primarily allows influx of calcium. The aim of the present study was to examine the effects of verapamil, as a calcium channel blocker, alone and its combination with glycine and/or glutamate on cardiac function, coronary flow, and oxidative stress in isolated rat heart or to examine the effects of potential activation of NMDA-R in isolated rat heart...
November 3, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27807405/glycine-potentiates-ampa-receptor-function-through-metabotropic-activation-of-glun2a-containing-nmda-receptors
#18
Li-Jun Li, Rong Hu, Brendan Lujan, Juan Chen, Jian-Jian Zhang, Yasuko Nakano, Tian-Yuan Cui, Ming-Xia Liao, Jin-Cao Chen, Heng-Ye Man, Hua Feng, Qi Wan
NMDA receptors are Ca(2+)-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function. Here we report that in cultured mouse hippocampal neurons, glycine increases AMPA receptor-mediated currents independent of the channel activity of NMDA receptors and the activation of glycine receptors. The potentiation of AMPA receptor function by glycine is antagonized by the inhibition of ERK1/2...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27797796/glycine-receptor-antibody-associated-epilepsy-in-a-boy-aged-4%C3%A2-years
#19
Chinwe Ude, Gautam Ambegaonkar
Our patient was a previously normal boy who presented to his local hospital with an explosive onset of prolonged seizures and encephalopathy. He was treated for a presumed central nervous system infection and initial neuroimaging was normal. Despite treatment with antibiotics and antiepileptic drugs (AEDs), he remained encephalopathic and became ataxic over the next 48 hours, not related to medication. The seizures also proved resistant to treatment despite polytherapy with AEDs, and he required immune-modulatory treatment, intravenous methylprednisolone and intravenous immunoglobulin, in addition to the AEDs to achieve seizure control...
October 19, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27791085/molecular-lock-regulates-binding-of-glycine-to-a-primitive-nmda-receptor
#20
Alvin Yu, Robert Alberstein, Alecia Thomas, Austin Zimmet, Richard Grey, Mark L Mayer, Albert Y Lau
The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
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