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https://www.readbyqxmd.com/read/29675131/glycine-increases-insulin-sensitivity-and-glutathione-biosynthesis-and-protects-against-oxidative-stress-in-a-model-of-sucrose-induced-insulin-resistance
#1
Mohammed El-Hafidi, Martha Franco, Angélica Ruiz Ramírez, José Santamaria Sosa, José Antonio Pineda Flores, Ocarol López Acosta, Monserrath Chávez Salgado, Guillermo Cardoso-Saldaña
Oxidative stress and redox status play a central role in the link between insulin resistance (IR) and lipotoxicity in metabolic syndrome. This mechanistic link may involve alterations in the glutathione redox state. We examined the effect of glycine supplementation to diet on glutathione biosynthesis, oxidative stress, IR, and insulin cell signaling in liver from sucrose-fed (SF) rats characterized by IR and oxidative stress. Our hypothesis is that the correction of glutathione levels by glycine treatment leads to reduced oxidative stress, a mechanism associated with improved insulin signaling and IR...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29671916/assembly-and-annotation-of-a-draft-genome-sequence-for-glycine-latifolia-a-perennial-wild-relative-of-soybean
#2
Qiong Liu, Sungyul Chang, Glen L Hartman, Leslie L Domier
Glycine latifolia (Benth.) Newell & Hymowitz (2n=40), one of the 27 wild perennial relatives of soybean, possesses genetic diversity and agronomically favorable traits that are lacking in soybean. Here, we report the 939-Mb draft genome assembly of G. latifolia (PI 559298) using exclusively linked-reads sequenced from a single Chromium library. We organized scaffolds into 20 chromosome-scale pseudomolecules utilizing two genetic maps and the Glycine max (L.) Merr. genome sequence. High copy numbers of putative 91-bp centromere-specific tandem repeats were observed in consecutive blocks within predicted pericentromeric regions on several pseudomolecules...
April 19, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29670280/mechanism-of-nmda-receptor-channel-block-by-mk-801-and-memantine
#3
Xianqiang Song, Morten Ø Jensen, Vishwanath Jogini, Richard A Stein, Chia-Hsueh Lee, Hassane S Mchaourab, David E Shaw, Eric Gouaux
The NMDA (N-methyl-D-aspartate) receptor transduces the binding of glutamate and glycine, coupling it to the opening of a calcium-permeable ion channel 1 . Owing to the lack of high-resolution structural studies of the NMDA receptor, the mechanism by which ion-channel blockers occlude ion permeation is not well understood. Here we show that removal of the amino-terminal domains from the GluN1-GluN2B NMDA receptor yields a functional receptor and crystals with good diffraction properties, allowing us to map the binding site of the NMDA receptor blocker, MK-801...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29662311/the-95-rgd-97-sequence-on-the-a%C3%AE-chain-of-fibrinogen-is-essential-for-binding-to-its-erythrocyte-receptor
#4
Filomena A Carvalho, Ana Filipa Guedes, Cedric Duval, Fraser L Macrae, Luke Swithenbank, David H Farrell, Robert As Ariëns, Nuno C Santos
Background: Erythrocyte aggregation, a cardiovascular risk factor, is increased by high plasma fibrinogen levels. Here, the effect of different fibrinogen mutations on binding to its human erythrocyte receptor was assessed in order to identify the interaction sites. Methods: Three fibrinogen variants were tested, specifically mutated in their putative integrin recognition sites on the Aα chain (mutants D97E, D574E and D97E/D574E) and compared with wild-type fibrinogen...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29660585/real-time-quartz-crystal-microbalance-cytosensor-based-on-a-signal-recovery-strategy-for-in-situ-and-continuous-monitoring-of-multiple-cell-membrane-glycoproteins
#5
Bin Zhou, Yan Hao, Dongping Long, Peihui Yang
A real-time quartz crystal microbalance (QCM) cytosensor based on a signal recovery strategy was first developed for in-situ and continuous monitoring of multiple cell membrane glycoproteins. In this work, gold nanoparticles (AuNPs) were linked with ligands to fabricate ligand-functionalized mass nanoprobes with signal amplification for increasing monitoring sensitivity. The mass nanoprobes bound to cell surface could be eluted with glycine-hydrochloric acid buffer, which led to a quick recovery of resonance frequency...
March 28, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29652126/initial-cell-adhesion-onto-a-phospholipid-polymer-brush-surface-modified-with-a-terminal-cell-adhesion-peptide
#6
Yuuki Inoue, Yuya Onodera, Kazuhiko Ishihara
Dynamic changes in the properties of adsorbed protein layers at material surfaces make it difficult to analyze a cell adhesion behavior. Adhesion is affected by the ligand molecules in the adsorbed protein layers on the material's surface. This study aimed to quantitatively analyze the initial cell adhesion onto a polymeric surface modified with immobilized cell adhesion molecules with a well-defined structure. Peptides containing an arginine-glycine-aspartic acid (RGD) sequence were introduced at almost all the termini of the grafted poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC)) chains using a click reaction at a highly protein-resistant poly(MPC) brush layer...
April 13, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29651041/duplication-and-diversification-of-lectin-receptor-like-kinases-lecrlk-genes-in-soybean
#7
Ping-Li Liu, Yuan Huang, Peng-Hao Shi, Meng Yu, Jian-Bo Xie, LuLu Xie
Lectin receptor-like kinases (LecRLKs) play important roles in plant development and stress responses. Although genome-wide studies of LecRLKs have been performed in several species, a comprehensive analysis including evolutionary, structural and functional analysis has not been carried out in soybean (Glycine max). In this study, we identified 185 putative LecRLK genes in the soybean genome, including 123 G-type, 60 L-type and 2 C-type LecRLK genes. Tandem duplication and segmental duplication appear to be the main mechanisms of gene expansion in the soybean LecRLK (GmLecRLK) gene family...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29648983/enhancement-of-brain-d-serine-mediates-recovery-of-cognitive-function-after-tbi
#8
Sigal Liraz-Zaltsman, Barbara Slusher, Dana Atrakchi-Baranes, Kinneret Rosenblatt, Yael Friedman Levi, Efrat Leah Kesner, Alcino J Silva, Anat Biegon, Esther Shohami
Cognitive deficits, especially memory loss, are common and devastating neuropsychiatric sequelae of traumatic brain injury (TBI). The deficits may persist for a long time and may be accompanied by increased risk of developing early onset dementia. Past attempts to reverse the neuropsychological effects of brain injury with glutamate-N-methyl-D-aspartate (NMDA) antagonists failed to show any benefits or worsened the outcome, suggesting activation, rather than blockage, of the NMDA receptor (NMDAR) may be useful in the sub-acute period after TBI and stroke...
March 14, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29644724/a-novel-missense-mutation-in-grin2a-causes-a-nonepileptic-neurodevelopmental-disorder
#9
Ana Fernández-Marmiesse, Hirofumi Kusumoto, Saray Rekarte, Iria Roca, Jin Zhang, Scott J Myers, Stephen F Traynelis, Mª Luz Couce, Luis Gutierrez-Solana, Hongjie Yuan
BACKGROUND: Mutations in the GRIN2A gene, which encodes the GluN2A (glutamate [NMDA] receptor subunit epsilon-1) subunit of the N-methyl-d-aspartate receptor, have been identified in patients with epilepsy-aphasia spectrum disorders, idiopathic focal epilepsies with centrotemporal spikes, and epileptic encephalopathies with severe developmental delay. However, thus far, mutations in this gene have not been associated with a nonepileptic neurodevelopmental disorder with dystonia. OBJECTIVES: The objective of this study was to identify the disease-causing gene in 2 siblings with neurodevelopmental and movement disorders with no epileptiform abnormalities...
April 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29642764/distinct-effects-of-resveratrol-on-seizures-and-hyperexcitability-induced-by-nmda-and-4-aminopyridine
#10
Ya-Jean Wang, Chung-Pin Hsieh, Ming-Huan Chan, Tzu-Yi Chan, Linyi Chen, Hwei-Hisen Chen
OBJECTIVES: The antiepileptic activity of resveratrol has been revealed in various experimental models of epilepsy. The present study evaluated the effects of resveratrol on the seizures and hyperexcitable neuronal activity associated with activation of N-methyl-d-aspartic acid (NMDA) receptor and inhibition of voltage-gated potassium channels. METHODS: The effects of resveratrol on seizure thresholds, excitatory field potentials (EFPs) and action potentials induced by NMDA and 4-aminopyridine (4-AP) were monitored in mice, the mouse cortical slices and rat cortical neurons, respectively...
April 12, 2018: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29596830/liposome-encapsulated-clodronate-specifically-depletes-spinal-microglia-and-reduces-initial-neuropathic-pain
#11
Yi-Rui Wang, Xiao-Fang Mao, Hai-Yun Wu, Yong-Xiang Wang
Liposome-encapsulated clodronate (LEC) is a specific depletor of macrophages. Our study characterized the LEC depletory effects, given intrathecally, on spinal microglia and assessed its effects on initiation and maintenance of neuropathic pain. Measured by using the MTT assay, LEC treatment specifically inhibited cell viability of cultured primary microglia, but not astrocytes or neurons, from neonatal rats, with an IC50 of 43 μg/mL. In spinal nerve ligation-induced neuropathic rats, pretreatment (1 day but not 5 days earlier) with intrathecal LEC specifically depleted microglia (but not astrocytes or neurons) in both contralateral and ipsilateral dorsal horns by the same degree (63% vs...
March 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29590749/discovery-of-a-potent-4r-5s-4-fluoro-5-methylproline-sulfonamide-transient-receptor-potential-ankyrin-1-trpa1-antagonist-and-its-methylene-phosphate-prodrug-guided-by-molecular-modeling
#12
Huifen Chen, Matthew Volgraf, Steven Do, Aleksandr Kolesnikov, Daniel G Shore, Vishal A Verma, Elisia Villemure, Lan Wang, Yong Chen, Baihua Hu, Ai-Jun Lu, Guosheng Wu, Xiaofeng Xu, Po-Wai Yuen, Yamin Zhang, Shawn D Erickson, Martin Dahl, Christine Brotherton-Pleiss, Suzanne Tay, Justin Q Ly, Lesley J Murray, Jun Chen, Desiree Amm, Wienke Lange, David H Hackos, Rebecca M Reese, Shannon D Shields, Joseph P Lyssikatos, Brian S Safina, Anthony A Estrada
TRPA1 is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To study its function in various disease contexts, we sought to identify novel, potent and selective small molecule TRPA1 antagonists. Herein we describe the evolution of an N-isopropyl glycine sulfonamide lead (1) to a novel and potent (4R,5S)-4-fluoro-5-methylproline sulfonamide series of inhibitors...
March 29, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29590630/two-differential-binding-mechanisms-of-fg-nucleoporins-and-nuclear-transport-receptors
#13
Piau Siong Tan, Iker Valle Aramburu, Davide Mercadante, Swati Tyagi, Aritra Chowdhury, Daniel Spitz, Sarah L Shammas, Frauke Gräter, Edward A Lemke
Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29588042/insights-into-receptor-based-anesthetic-pharmacophores-and-anesthetic-protein-interactions
#14
Victoria S Fahrenbach, Edward J Bertaccini
General anesthetics are thought to allosterically bind and potentiate the inhibitory currents of the GABAA receptor through drug-specific binding sites. The physiologically relevant isoform of the GABAA receptor is a transmembrane ligand-gated ion channel consisting of five subunits (γ-α-β-α-β linkage) symmetrically arranged around a central chloride-conducting pore. Although the exact molecular structure of this heteropentameric GABAA receptor remains unknown, molecular modeling has allowed significant advancements in understanding anesthetic binding and action...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29587637/combining-qtl-seq-and-linkage-mapping-to-fine-map-a-wild-soybean-allele-characteristic-of-greater-plant-height
#15
Xiaoli Zhang, Wubin Wang, Na Guo, Youyi Zhang, Yuanpeng Bu, Jinming Zhao, Han Xing
BACKGROUND: Plant height (PH) is an important agronomic trait and is closely related to yield in soybean [Glycine max (L.) Merr.]. Previous studies have identified many QTLs for PH. Due to the complex genetic background of PH in soybean, there are few reports on its fine mapping. RESULTS: In this study, we used a mapping population derived from a cross between a chromosome segment substitution line CSSL3228 (donor N24852 (G. Soja), a receptor NN1138-2 (G. max)) and NN1138-2 to fine map a wild soybean allele of greater PH by QTL-seq and linkage mapping...
March 27, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29587443/the-horizon-of-a-therapy-for-rare-genetic-diseases-a-druggable-future-for-fibrodysplasia-ossificans-progressiva
#16
REVIEW
Serena Cappato, Francesca Giacopelli, Roberto Ravazzolo, Renata Bocciardi
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition characterized by progressive extra-skeletal ossification leading to cumulative and severe disability. FOP has an extremely variable and episodic course and can be induced by trauma, infections, iatrogenic harms, immunization or can occur in an unpredictable way, without any recognizable trigger. The causative gene is ACVR1 , encoding the Alk-2 type I receptor for bone morphogenetic proteins (BMPs). The signaling is initiated by BMP binding to a receptor complex consisting of type I and II molecules and can proceed into the cell through two main pathways, a canonical, SMAD-dependent signaling and a p38-mediated cascade...
March 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29567093/n-oleoyl-glycine-reduces-nicotine-reward-and-withdrawal-in-mice
#17
Giulia Donvito, Fabiana Piscitelli, Pretal Muldoon, Asti Jackson, Rosa Maria Vitale, Enrico D'Aniello, Catia Giordano, Bogna M Ignatowska-Jankowska, Mohammed A Mustafa, Francesca Guida, Gavin N Petrie, Linda Parker, Reem Smoum, Laura Sim-Selley, Sabatino Maione, Aron H Lichtman, M Imad Damaj, Vincenzo Di Marzo, Raphael Mechoulam
Cigarette smokers with brain damage involving the insular cortex display cessation of tobacco smoking, suggesting that this region may contribute to nicotine addiction. In the present study, we speculated that molecules in the insular cortex that are sensitive to experimental traumatic brain injury (TBI) in mice might provide leads to ameliorate nicotine addiction. Using targeted lipidomics, we found that TBI elicited substantial increases of a largely uncharacterized lipid, N-acyl-glycine, N-oleoyl-glycine (OlGly), in the insular cortex of mice...
March 19, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29559921/nitric-oxide-orchestrates-a-power-law-modulation-of-sympathetic-firing-behaviors-in-neonatal-rat-spinal-cords
#18
Chun-Kuei Su, Yi-Yin Chen, Chiu-Ming Ho
Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29559876/dietary-glycine-is-rate-limiting-for-glutathione-synthesis-and-may-have-broad-potential-for-health-protection
#19
REVIEW
Mark F McCarty, James H O'Keefe, James J DiNicolantonio
Background: Glutathione is a key scavenging antioxidant that opposes the proinflammatory signaling of hydrogen peroxide. Boosting cellular glutathione levels may have broad utility in the prevention and treatment of disorders driven by oxidative stress. Supplemental N-acetylcysteine has been employed for this purpose. Could supplemental glycine likewise promote glutathione synthesis? Methods: We conducted a review of the pertinent literature using PubMed. Results: Tissue glycine levels are lower than the glutathione synthase Michaelis constant (Km ) for glycine...
2018: Ochsner Journal
https://www.readbyqxmd.com/read/29556099/an-optically-controlled-probe-identifies-lipid-gating-fenestrations-within-the-trpc3-channel
#20
Michaela Lichtenegger, Oleksandra Tiapko, Barbora Svobodova, Thomas Stockner, Toma N Glasnov, Wolfgang Schreibmayer, Dieter Platzer, Gema Guedes de la Cruz, Sarah Krenn, Romana Schober, Niroj Shrestha, Rainer Schindl, Christoph Romanin, Klaus Groschner
Transient receptor potential canonical (TRPC) channels TRPC3, TRPC6 and TRPC7 are able to sense the lipid messenger diacylglycerol (DAG). The DAG-sensing and lipid-gating processes in these ion channels are still unknown. To gain insights into the lipid-sensing principle, we generated a DAG photoswitch, OptoDArG, that enabled efficient control of TRPC3 by light. A structure-guided mutagenesis screen of the TRPC3 pore domain unveiled a single glycine residue behind the selectivity filter (G652) that is exposed to lipid through a subunit-joining fenestration...
March 19, 2018: Nature Chemical Biology
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