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https://www.readbyqxmd.com/read/28306573/redefining-progressive-encephalomyelitis-with-rigidity-and-myoclonus-after-the-discovery-of-antibodies-to-glycine-receptors
#1
Sarah J Crisp, Bettina Balint, Angela Vincent
PURPOSE OF REVIEW: This review highlights the recent discovery of antibodies to glycine receptor (GlyR-Ab) and discusses the relationship between these antibodies and neurological disorders. RECENT FINDINGS: Since the initial description in 2008 of antibodies to glycine receptors (GlyR-Abs) in a patient with progressive encephalomyelitis with rigidity and myoclonus (PERM), these antibodies have been found in PERM and in some patients with a variety of stiff person spectrum (SPS) or related disorders...
March 16, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28302446/electrophysiological-evidence-of-increased-glycine-receptor-mediated-phasic-and-tonic-inhibition-by-blockade-of-glycine-transporters-in-spinal-superficial-dorsal-horn-neurons-of-adult-mice
#2
Misa Oyama, Seiya Kuraoka, Shun Watanabe, Takashi Iwai, Mitsuo Tanabe
To understand the synaptic and/or extrasynaptic mechanisms underlying pain relief by blockade of glycine transporter subtypes GlyT1 and GlyT2, whole-cell recordings were made from dorsal horn neurons in spinal slices from adult mice, and the effects of NFPS and ALX-1393, selective GlyT1 and GlyT2 inhibitors, respectively, on phasic evoked or miniature glycinergic inhibitory postsynaptic currents (eIPSCs or mIPSCs) were examined. NFPS and ALX-1393 prolonged the decay phase of eIPSCs without affecting their amplitude...
February 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28293849/inhibitors-of-ethylene-biosynthesis-and-signaling
#3
G Eric Schaller, Brad M Binder
Ethylene is a gas biosynthesized by plants which has many physiological and developmental effects on their growth. Ethylene affects agriculturally and horticulturally important traits such as fruit ripening, post-harvest physiology, senescence, and abscission, and so ethylene action is often inhibited to improve the shelf life of fruits, vegetables, and cut flowers. Chemical inhibitors of ethylene action are also useful for research to characterize the mechanisms of ethylene biosynthesis and signal transduction, and the role that ethylene plays in various physiological processes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28282425/administration-of-tranexamic-acid-to-patients-undergoing-surgery-for-adolescent-idiopathic-scoliosis-evokes-pain-and-increases-the-infusion-rate-of-remifentanil-during-the-surgery
#4
Nobuko Ohashi, Masayuki Ohashi, Naoto Endo, Tatsuro Kohno
BACKGROUND: We recently reported that tranexamic acid (TXA) evokes pain in rats by inhibiting γ-aminobutyric acid and glycine receptors on neurons in the spinal dorsal horn. Although TXA is commonly used to reduce perioperative blood loss during various surgeries, its potential to induce intraoperative nociception, thereby increasing the need for more analgesics during surgery, has not been investigated. Therefore, this study aimed to investigate whether TXA evokes pain and increases the need for a higher infusion rate of remifentanil in patients undergoing surgery for adolescent idiopathic scoliosis (AIS)...
2017: PloS One
https://www.readbyqxmd.com/read/28277064/inhibition-of-nmda-receptor-function-with-an-anti-glun1-s2-antibody-impairs-human-platelet-function-and-thrombosis
#5
Taryn N Green, Justin R Hamilton, Marie-Christine Morel-Kopp, Zhaohua Zheng, Ting-Yu T Chen, James I Hearn, Peng P Sun, Jack U Flanagan, Deborah Young, P Alan Barber, Matthew J During, Christopher M Ward, Maggie L Kalev-Zylinska
GluN1 is a mandatory component of N-methyl-D-aspartate receptors (NMDARs) best known for their roles in the brain, but with increasing evidence for relevance in peripheral tissues, including platelets. Certain anti-GluN1 antibodies reduce brain infarcts in rodent models of ischaemic stroke. There is also evidence that human anti-GluN1 autoantibodies reduce neuronal damage in stroke patients, but the underlying mechanism is unclear. This study investigated whether anti-GluN1-mediated neuroprotection involves inhibition of platelet function...
February 21, 2017: Platelets
https://www.readbyqxmd.com/read/28267198/serotonergic-transmission-at-merkel-discs-modulation-by-exogenously-applied-chemical-messengers-and-involvement-of-ih-currents
#6
Weipang Chang, Hirosato Kanda, Ryo Ikeda, Jennifer Ling, Jianguo G Gu
The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In the present study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers...
March 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28265071/bioinformatic-analysis-of-riboswitch-structures-uncovers-variant-classes-with-altered-ligand-specificity
#7
Zasha Weinberg, James W Nelson, Christina E Lünse, Madeline E Sherlock, Ronald R Breaker
Riboswitches are RNAs that form complex, folded structures that selectively bind small molecules or ions. As with certain groups of protein enzymes and receptors, some riboswitch classes have evolved to change their ligand specificity. We developed a procedure to systematically analyze known riboswitch classes to find additional variants that have altered their ligand specificity. This approach uses multiple-sequence alignments, atomic-resolution structural information, and riboswitch gene associations. Among the discoveries are unique variants of the guanine riboswitch class that most tightly bind the nucleoside 2'-deoxyguanosine...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28262924/2-methoxyestradiol-impacts-on-amino-acids-mediated-metabolic-reprogramming-in-osteosarcoma-cells-by-interaction-with-nmda-receptor
#8
Magdalena Gorska-Ponikowska, Ugo Perricone, Alicja Kuban-Jankowska, Giosue Lo Bosco, Giampaolo Barone
Deregulation of serine and glycine metabolism, have been identified to function as metabolic regulators in supporting tumor cell growth. The role of serine and glycine in regulation of cancer cell proliferation is complicated, dependent on concentrations of amino acids and tissue-specific. D-serine and glycine are coagonists of N-methyl-D-aspartate receptor subunit GRIN1. Importantly, NMDA receptors are widely expressed in cancer cells and play an important role in regulation of cell death, proliferation and metabolism of numerous malignancies...
March 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28256224/lipid-mediated-regulation-of-embedded-receptor-kinases-via-parallel-allosteric-relays
#9
Madhubrata Ghosh, Loo Chien Wang, Ranita Ramesh, Leslie K Morgan, Linda J Kenney, Ganesh S Anand
Membrane-anchored receptors are essential cellular signaling elements for stimulus sensing, propagation, and transmission inside cells. However, the contributions of lipid interactions to the function and dynamics of embedded receptor kinases have not been described in detail. In this study, we used amide hydrogen/deuterium exchange mass spectrometry, a sensitive biophysical approach, to probe the dynamics of a membrane-embedded receptor kinase, EnvZ, together with functional assays to describe the role of lipids in receptor kinase function...
February 28, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28254751/glycinergic-inhibition-of-bat-sympathetic-premotor-neurons-in-rostral-raphe-pallidus
#10
Ellen Paula Santos da Conceição, Christopher J Madden, Shaun F Morrison
The rostral raphe pallidus (rRPa) contains sympathetic premotor neurons controlling thermogenesis in brown adipose tissue (BAT). We sought to determine if a tonic activation of glycineA receptors (GlyAR) in the rRPa contributes to the inhibitory regulation of BAT SNA and of cardiovascular parameters in anesthetized rats. Nanoinjection of the GlyAR antagonist, strychnine (STR), into the rRPa of intact rats increased BAT sympathetic nerve activity (SNA, peak: +495%), BAT temperature (TBAT, +1.1 ºC), expired CO2, (+0...
March 2, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28249275/intestinal-farnesoid-x-receptor-signaling-modulates-metabolic-disease
#11
Frank J Gonzalez, Changtao Jiang, Cen Xie, Andrew D Patterson
Farnesoid X receptor (FXR) regulates the synthesis, transport and enterohepatic circulation of bile acids (BA) by modulating the expression of related genes in the liver and small intestine. The composition of the gut microbiota is correlated with metabolic diseases, notably obesity and non-alcoholic fatty acid disease (NAFLD). Recent studies revealed that bacterial metabolism of BA can modulate FXR signaling in the intestine by altering the composition and concentrations of FXR agonist and antagonist. FXR agonist enhances while FXR antagonist suppresses obesity, NAFLD and insulin resistance...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28245819/effects-of-sarcosine-and-n-n-dimethylglycine-on-nmda-receptor-mediated-excitatory-field-potentials
#12
Mei-Yi Lee, Yi-Ruu Lin, Yi-Shu Tu, Yufeng Jane Tseng, Ming-Huan Chan, Hwei-Hsien Chen
BACKGROUND: Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system...
February 28, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28242877/epilepsy-associated-grin2a-mutations-reduce-nmda-receptor-trafficking-and-agonist-potency-molecular-profiling-and-functional-rescue
#13
L Addis, J K Virdee, L R Vidler, D A Collier, D K Pal, D Ursu
Mutations in the N-methyl-D-aspartate receptor (NMDAR) gene GRIN2A cause epilepsy-aphasia syndrome (EAS), a spectrum of epileptic, cognitive and language disorders. Using bioinformatic and patient data we shortlisted 10 diverse missense mutations for characterisation. We used high-throughput calcium-flux assays and patch clamp recordings of transiently transfected HEK-293 cells for electrophysiological characterization, and Western blotting and confocal imaging to assay expression and surface trafficking. Mutations P79R, C231Y, G483R and M705V caused a significant reduction in glutamate and glycine agonist potency, whilst D731N was non-responsive...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28237886/ligand-peptide-grafted-pegylated-liposomes-using-her2-targeted-peptide-lipid-derivatives-for-targeted-delivery-in-breast-cancer-cells-the-effect-of-serine-glycine-repeated-peptides-as-a-spacer
#14
Tadaharu Suga, Yuki Fuchigami, Masayori Hagimori, Shigeru Kawakami
Ligand peptide-grafted PEGylated liposomes have been widely studied for targeted drug delivery systems. Because ligand peptides are commonly grafted using PEG as a spacer on the surface of PEGylated liposomes, the interaction between ligand peptides and their corresponding receptors can be interrupted by steric hindrance of the PEG layer. Therefore, we aimed to develop ligand peptide-lipid derivatives to enhance the targeting efficiency of ligand peptide-grafted PEGylated liposomes, and designed a new ligand peptide-lipid derivatives having serine-glycine repeats (SG)n as a spacer based on the peptide length calculated by PyMol (v0...
February 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28235687/immodin-and-its-immune-system-supportive-role-in-paclitaxel-therapy-of-4t1-mouse-breast-cancer
#15
Vlasta Demečková, Peter Solár, Gabriela Hrčková, Dagmar Mudroňová, Bianka Bojková, Monika Kassayová, Soňa Gancarčiková
It is evident that standard chemotherapy agents may have an impact on both tumor and host immune system. Paclitaxel (PTX), a very potent anticancer drug from a taxane family, has achieved prominence in clinical oncology for its efficacy against a wide range of tumors including breast cancer. However, significant toxicity, such as myelosuppression, limit the effectiveness of Paclitaxel-based treatment regimens. Immodin (IM) is low molecular dialysate fraction of homogenate made from human leukocytes. It contains a mixture of substances from which so far have been described e...
February 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28228639/grin1-mutation-associated-with-intellectual-disability-alters-nmda-receptor-trafficking-and-function
#16
Wenjuan Chen, Christine Shieh, Sharon A Swanger, Anel Tankovic, Margaret Au, Marianne McGuire, Michele Tagliati, John M Graham, Suneeta Madan-Khetarpal, Stephen F Traynelis, Hongjie Yuan, Tyler Mark Pierson
N-methyl-d-aspartate receptors (NMDARs) play important roles in brain development and neurological disease. We report two individuals with similar dominant de novo GRIN1 mutations (c.1858 G>A and c.1858 G>C; both p.G620R). Both individuals presented at birth with developmental delay and hypotonia associated with behavioral abnormalities and stereotypical movements. Recombinant NMDARs containing the mutant GluN1-G620R together with either GluN2A or GluN2B were evaluated for changes in their trafficking to the plasma membrane and their electrophysiological properties...
February 23, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28228087/beyond-ketamine-new-approaches-to-the-development-of-safer-antidepressants
#17
Shigeyuki Chaki
Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention...
February 20, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28222651/levodopa-placebo-and-rotigotine-change-biomarker-levels-for-oxidative-stress
#18
Siegfried Muhlack, Manuel Kinkel, Lennard Herrman, Thomas Müller
INTRODUCTION: Homocysteine increase and glutathione derivative cysteinyl-glycine fall are indirect biomarkers for oxidative stress, for instance due to dopamine D1 receptor stimulation. OBJECTIVES: To investigate the influence of the D1 receptor agonists levodopa and rotigotine compared with placebo on homocysteine and cysteinyl-glycine in plasma of patients with Parkinson's disease. METHODS: Patients received 100 mg levodopa, 4 mg rotigotine or placebo...
February 22, 2017: Neurological Research
https://www.readbyqxmd.com/read/28202787/dysregulated-glycine-signaling-contributes-to-increased-impulsivity-during-protracted-alcohol-abstinence
#19
Cristina Irimia, Matthew W Buczynski, Luis A Natividad, Sarah A Laredo, Nathaniel Avalos, Loren H Parsons
Persons with alcoholism who are abstinent exhibit persistent impairments in the capacity for response inhibition, and this form of impulsivity is significantly associated with heightened relapse risk. Brain-imaging studies implicate aberrant prefrontal cortical function in this behavioral pathology, although the underlying mechanisms are not understood. Here we present evidence that deficient activation of glycine and serine release in the ventral medial prefrontal cortex (vmPFC) contributes to increased motor impulsivity during protracted abstinence from long-term alcohol exposure...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#20
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
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