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Sangyun Lee, Heather B Mayes, Jessica M J Swanson, Gregory A Voth
The ClC family of transmembrane proteins functions throughout nature to control the transport of Cl- ions across biological membranes. ClC-ec1 from Escherichia coli is an antiporter, coupling the transport of Cl- and H+ ions in opposite directions and driven by the concentration gradients of the ions. Despite keen interest in this protein, the molecular mechanism of the Cl-/H+ coupling has not been fully elucidated. Here, we have used multiscale simulation to help identify the essential mechanism of the Cl-/H+ coupling...
October 26, 2016: Journal of the American Chemical Society
S O Vechkapova, T A Zapara, E A Morozova, A L Proskura, E E Schul'ts, T G Tolstikova, A S Ratushnyak
Amide of lambertian acid suppresses hyperactivation of inotropic glutamate receptors in hippocampal sections induced by a decrease in the level of magnesium ions (a selective blocker of glutamate NMDA receptors). Treatment of the sections with amide of lambertian acid in standard physiological saline does not prevent development of NMDA-dependent synaptic potentiation. Lambertian acid isolated from needles and turpentine of Siberian pine (Pinus sibirica R. Mayr), and its derivatives may become a source of substances with glutamatergic mechanism of action for treatment of cognitive and neurodegenerative disorders...
October 26, 2016: Bulletin of Experimental Biology and Medicine
Jennifer Hochheim, Angela Kranz, Karin Krumbach, Sascha Sokolowsky, Lothar Eggeling, Stephan Noack, Marco Bocola, Michael Bott, Jan Marienhagen
OBJECTIVES: To explore systemic effects of mutations in the UDP-N-acetylmuramoylalanyl-D-glutamate 2,6-diaminopimelate ligase (MurE) of Corynebacterium glutamicum, that leads to extracellular L-lysine accumulation by this bacterium. RESULTS: The analysis of a mutant cohort of C. glutamicum strains carrying all possible 20 amino acids at position 81 of MurE revealed unexpected effects on cellular properties. With increasing L-lysine accumulation the growth rate of the producing strain is reduced...
October 25, 2016: Biotechnology Letters
Chao Zhang, Chendan Wang, Jianbo Ren, Xiangjie Guo, Keming Yun
Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes...
October 24, 2016: International Journal of Molecular Sciences
M Chevallet, B Gallet, A Fuchs, P H Jouneau, K Um, E Mintz, I Michaud-Soret
Increased production and use of zinc oxide nanoparticles (ZnO-NPs) in consumer products has prompted the scientific community to investigate their potential toxicity, and understand their impact on the environment and organisms. Molecular mechanisms involved in ZnO-NP toxicity are still under debate and focus essentially on high dose expositions. In our study, we chose to evaluate the effect of sub-toxic doses of ZnO-NPs on human hepatocytes (HepG2) with a focus on metal homeostasis and redox balance disruptions...
October 26, 2016: Nanoscale
Ioline D Henter, Rafael T de Sousa, Philip W Gold, Andre R Brunoni, Carlos A Zarate, Rodrigo Machado-Vieira
Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas Covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators...
October 26, 2016: Expert Review of Clinical Pharmacology
Catherine Lebel, Frank P MacMaster, Deborah Dewey
INTRODUCTION: Language acquisition occurs rapidly during early childhood and lays the foundation for future reading success. However, little is known about the brain-language relationships in young children. The goal of this study was to investigate relationships between brain metabolites and prereading language abilities in healthy preschool-aged children. METHODS: Participants were 67 healthy children aged 3.0-5.4 years scanned on a 3T GE MR750w MRI scanner using short echo proton spectroscopy with a voxel placed in the anterior cingulate gyrus (n = 56) and/or near the left angular gyrus (n = 45)...
October 2016: Brain and Behavior
Tathyana Mar Amorim Franco, Subray S Hegde, John S Blanchard
The biosynthetic pathway of the branched-chain amino acids is essential for M. tuberculosis growth and survival. We report here the kinetic and chemical mechanism of the pyridoxal 5'-phosphate (PLP)-dependent branched-chain aminotransferase, IlvE, from M. tuberculosis (MtIlvE). This enzyme is responsible for the final step of the synthesis of the branched-chain amino acids isoleucine, leucine and valine. As seen in other aminotransferases, MtIlvE displays a ping-pong kinetic mechanism. pK values were identified from the pH dependence on V as well as V/K, indicating that the phosphate ester of the PLP cofactor, as well as the α-amino group from L-glutamate and the active site Lys204, play roles in acid-base catalysis and binding, respectively...
October 25, 2016: Biochemistry
Zacharias G Laoutidis, Georgia E Lekka, Kanellos T Kioulos
OBJECTIVE: The aim of the present study was to review the existing literature on clinical trials with glutamatergic agents in adults with obsessive-compulsive disorder (OCD) and to perform a meta-analysis to estimate the overall effect size. DATA SOURCES: We searched in MEDLINE, Embase, and the Cochrane Library for eligible studies, using the following search terms: (glutamate OR glutaminergic OR glutamatergic OR NMDA OR AMPA OR kainate) AND (obsessive-compulsive disorder OR obsessive OR compulsive OR OCD)...
October 25, 2016: Journal of Clinical Psychiatry
Chimoné S Dalton, Karen van de Rakt, Åsa Fahlman, Kathreen Ruckstuhl, Peter Neuhaus, Richard Popko, Susan Kutz, Frank van der Meer
Herpesviruses (HVs) have a wide range of hosts in the animal kingdom. The result of infection with HVs can vary from asymptomatic to fatal diseases depending on subtype, strain, and host. To date, little is known about HVs naturally circulating in wildlife species and the impact of these viruses on other species. In our study, we used genetic and comparative approaches to increase our understanding of circulating HVs in Canadian wildlife. Using nested polymerase chain reaction targeting a conserved region of the HV DNA polymerase gene, we analyzed material derived from wildlife of western and northern Canada collected between February 2009 and Sept 2014...
October 24, 2016: Archives of Virology
Hengjia Ni, Lu Lu, Jinpin Deng, Wenjun Fan, Tiejun Li, Jiming Yao
Background. Oxidative stress is associated with infertility. This study was conducted to determine the effects of glutamate and aspartate on serum antioxidative enzymes, sex hormones, and genital inflammation in boars suffering from oxidative stress. Methods. Boars were randomly divided into 4 groups: the nonchallenged control (CON) and H2O2-challenged control (BD) groups were fed a basal diet supplemented with 2% alanine; the other two groups were fed the basal diet supplemented with 2% glutamate (GLU) or 2% aspartate (ASP)...
2016: Mediators of Inflammation
Eric K S Shim, Gleen F Chandra, S Pedireddy, Soo-Y Lee
Edible bird's nest (EBN) is made from the glutinous salivary secretion of highly concentrated mucin glycoprotein by swiftlets (genus Aerodramus or Collocalia) native to the Indo-Pacific region. The unique Raman spectrum of EBN has vibrational lines that can be assigned to peptides and saccharides in the glycoprotein, and it can be used to screen for adulteration. The common edible adulterants classified into two types. Type I adulterants, such as fish bladder, pork skin, karaya gum, coralline seaweed, agar strips, and tremella fungus, were solids which adhered externally on the surface of the EBN cement...
September 2016: Journal of Food Science and Technology
M-L Wong, M Arcos-Burgos, S Liu, J I Vélez, C Yu, B T Baune, M C Jawahar, V Arolt, U Dannlowski, A Chuah, G A Huttley, R Fogarty, M D Lewis, S R Bornstein, J Licinio
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD)...
October 25, 2016: Molecular Psychiatry
Ling Fan, Zhao Chen, Wenbin Fu, Nenggui Xu, Jianhua Liu, Aiping Lu, Ziping Li, Shengyong Su, Taixiang Wu, Aihua Ou
This study aims to investigate the molecular mechanisms of acupuncture in the remission of depression. A depressive disorder model was induced by exposing Sprague-Dawley rats to chronic unpredictable stress. The rats were divided into five groups: healthy (blank group) and stressed rats (model group), and stressed rats treated with acupuncture (acupuncture group), riluzole (riluzole group), acupuncture combined with botulinum toxin A (BTX-A) injection (acupuncture+BTX-A group) or riluzole combined with BTX-A injection (riluzole+BTX-A group)...
October 2016: Journal of Acupuncture and Meridian Studies
Lucia L Prieto-Godino, Raphael Rytz, Benoîte Bargeton, Liliane Abuin, J Roman Arguello, Matteo Dal Peraro, Richard Benton
Pseudogenes are generally considered to be non-functional DNA sequences that arise through nonsense or frame-shift mutations of protein-coding genes. Although certain pseudogene-derived RNAs have regulatory roles, and some pseudogene fragments are translated, no clear functions for pseudogene-derived proteins are known. Olfactory receptor families contain many pseudogenes, which reflect low selection pressures on loci no longer relevant to the fitness of a species. Here we report the characterization of a pseudogene in the chemosensory variant ionotropic glutamate receptor repertoire of Drosophila sechellia, an insect endemic to the Seychelles that feeds almost exclusively on the ripe fruit of Morinda citrifolia...
October 24, 2016: Nature
Cathy Joanna Jensen, Frauke Demol, Romy Bauwens, Ron Kooijman, Ann Massie, Agnès Villers, Laurence Ris, Jacques De Keyser
In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the β2-adrenergic receptor on astrocytes might contribute to this energy balance, it has not yet been shown conclusively in vivo. Inducible astrocyte specific β2-adrenergic receptor knock-out mice were generated by crossing homozygous β2-adrenergic receptor floxed mice (Adrb2flox) and mice with heterozygous tamoxifen-inducible Cre recombinase-expression driven by the astrocyte specific L-glutamate/L-aspartate transporter promoter (GLAST-CreERT2)...
2016: PloS One
Kaixuan Ren, Haitao Cui, Qinghua Xu, Chaoliang He, Gao Li, Xuesi Chen
Bone marrow-derived mesenchymal stem cells (BMSCs) possess vast potential for tissue engineering and regenerative medicine. In this study, an injectable hydrogel comprising poly(L-glutamic acid)-graft-tyramine (PLG-g-TA) with tunable microenvironment was developed via enzyme-catalyzed crosslinking, and used as artificial extracellular matrix (ECM) to explore the behaviors of BMSCs during three dimensional (3D) culture. It was found that the mechanical property, porous structure as well as degradation process of the hydrogels could be tuned by changing the copolymer concentration...
October 24, 2016: Biomacromolecules
Anusha Mishra, James P Reynolds, Yang Chen, Alexander V Gourine, Dmitri A Rusakov, David Attwell
Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies blood oxygen level-dependent functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptor 5 (mGluR5) on astrocytes, evoking Ca(2+) release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knockout of the inositol 1,4,5-trisphosphate receptors that release Ca(2+) from stores does not affect neurovascular coupling...
October 24, 2016: Nature Neuroscience
G Mkrtchyan, A Graf, L Bettendorff, V Bunik
Decreased thiamine and reduced activity of thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase (OGDH) cause neurodegeneration. We hypothesized on concerted cell-specific regulation of the thiamine metabolism and ThDP-dependent reactions. We identified a smaller thiamine pool, a lower expression of the mitochondrial ThDP transporter, and a higher expression of OGDH in rat astrocytes versus neuroblastoma N2A. According to the data, the astrocytic OGDH may be up-regulated by an increase in intracellular ThDP, while the neuroblastomal OGDH functions at full ThDP saturation...
October 20, 2016: Neurochemistry International
Courtney L Huff, Rachel L Morano, James P Herman, Bryan K Yamamoto, Gary A Gudelsky
3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation...
October 20, 2016: Neurotoxicology
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