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https://www.readbyqxmd.com/read/29236991/neurochemical-changes-in-the-medial-wall-of-the-brain-in-chronic-migraine
#1
David M Niddam, Kuan-Lin Lai, Shang-Yueh Tsai, Yi-Ru Lin, Wei-Ta Chen, Jong-Ling Fuh, Shuu-Jiun Wang
Migraine chronification is associated with a dysfunctional thalamocortical pathway. The present study addressed whether abnormal concentrations of neurochemicals exist in key brain regions of this pathway in chronic migraine. Magnetic resonance spectroscopic imaging of the bilateral medial walls of the brain was used to measure choline, creatine, glutamate and glutamine, myo-inositol, and N-acetyl-aspartate in chronic migraine patients and in matched groups of episodic migraine patients and healthy controls...
December 11, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29234335/metabolite-profiling-of-wheat-seedlings-induced-by-chitosan-revelation-of-the-enhanced-carbon-and-nitrogen-metabolism
#2
Xiaoqian Zhang, Kecheng Li, Ronge Xing, Song Liu, Pengcheng Li
Chitosan plays an important role in regulating growth and eliciting defense in many plant species. However, the exact metabolic response of plants to chitosan is still not clear. The present study performed an integrative analysis of metabolite profiles in chitosan-treated wheat seedlings and further investigated the response of enzyme activities and transcript expression related to the primary carbon (C) and nitrogen (N) metabolism. Metabolite profiling revealed that chitosan could induce significant difference of organic acids, sugars and amino acids in leaves of wheat seedlings...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29233555/human-neural-stem-cell-transplantation-rescues-functional-deficits-in-r6-2-and-q140-huntington-s-disease-mice
#3
Jack C Reidling, Aroa Relaño-Ginés, Sandra M Holley, Joseph Ochaba, Cindy Moore, Brian Fury, Alice Lau, Andrew H Tran, Sylvia Yeung, Delaram Salamati, Chunni Zhu, Asa Hatami, Carlos Cepeda, Joshua A Barry, Talia Kamdjou, Alvin King, Dane Coleal-Bergum, Nicholas R Franich, Frank M LaFerla, Joan S Steffan, Mathew Blurton-Jones, Charles K Meshul, Gerhard Bauer, Michael S Levine, Marie-Francoise Chesselet, Leslie M Thompson
Huntington's disease (HD) is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT) gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP)-grade human embryonic stem cell-derived neural stem cell (hNSC) line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells...
December 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29230814/nigella-sativa-l-as-an-alternative-antibiotic-feed-supplement-and-effect-on-growth-performance-in-weanling-pigs
#4
Branko T Petrujkić, Ross C Beier, Haiqi He, Kenneth J Genovese, Christina L Swaggerty, Michael E Hume, Tawni L Crippen, Roger B Harvey, Robin C Anderson, David J Nisbet
BACKGROUND: Nigella sativa L. (NS) is a plant containing bioactive constituents like thymoquinone. Extracts of NS improve performance and reduce enteropathogen colonization in poultry and small ruminants but studies with swine are lacking. In two different studies oral administration of NS extracts at doses equivalent to 0, 1.5 and 4.5 g extract kg-1 diet was assessed on piglet performance and intestinal carriage of wildtype Escherichia coli and Campylobacter, and Salmonella Typhimurium...
December 11, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29230490/pharmacokinetic-study-of-tianeptine-and-its-active-metabolite-mc5-in-rats-following-different-routes-of-administration-using-a-novel-liquid-chromatography-tandem-mass-spectrometry-analytical-method
#5
Małgorzata Szafarz, Agnieszka Wencel, Krzysztof Pociecha, Filip A Fedak, Piotr Wlaź, Elżbieta Wyska
Tianeptine is an atypical antidepressant with a unique mechanism of action and recently it has been also reported that its major metabolite, compound MC5, possesses pharmacological activity similar to that of the parent drug. The current study aims to investigate the pharmacokinetics (PK) of both tianeptine and MC5 after intravenous or intraperitoneal administration of the parent drug as well as the metabolic ratio of MC5 in rats. To achieve these goals an LC-MS/MS method using the small sample volume for the quantitation of tianeptine and its active metabolite MC5 in rat plasma and liver perfusate has been developed and validated...
December 12, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29229845/brain-urea-increase-is-an-early-huntington-s-disease-pathogenic-event-observed-in-a-prodromal-transgenic-sheep-model-and-hd-cases
#6
Renee R Handley, Suzanne J Reid, Rudiger Brauning, Paul Maclean, Emily R Mears, Imche Fourie, Stefano Patassini, Garth J S Cooper, Skye R Rudiger, Clive J McLaughlan, Paul J Verma, James F Gusella, Marcy E MacDonald, Henry J Waldvogel, C Simon Bawden, Richard L M Faull, Russell G Snell
The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73-line sheep expressing a human CAG-expansion HTT cDNA transgene...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-glp-1-is-governed-by-an-activated-glutamate-dehydrogenase
#7
Lotta E Andersson, Liliya Shcherbina, Mahmoud Al-Majdoub, Neelanjan Vishnu, Claudia Balderas Arroyo, Jonathan Aste Carrara, Claes B Wollheim, Malin Fex, Hindrik Mulder, Nils Wierup, Peter Spégel
Glucagon-like peptide-1 (GLP-1), secreted from intestinal L-cells, glucose-dependently stimulates insulin secretion from beta-cells. This glucose-dependence prevents hypoglycemia, rendering GLP-1 analogues a useful and safe treatment modality in type-2 diabetes. While the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear.We investigated how GLP-1 secretion is metabolically coupled in L-cells (GLUTag) and in vivo in mice, using the insulin-secreting cell-line INS-1 832/13 as reference...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29227501/chondrogenic-potential-of-macroporous-biodegradable-cryogels-based-on-synthetic-poly-%C3%AE-amino-acids
#8
T Sedlačík, O K Acar, H Studenovská, I Kotelnikov, J Kučka, Z Konečná, T Zikmund, J Kaiser, G T Kose, F Rypáček
In this study, the potential of highly porous hydrogels based on biodegradable synthetic poly(α-amino acids) to support proliferation and chondrogenesis of human dental pulp stem cells (hDPSCs) was investigated. Covalently crosslinked gels with permanent pores were formed under cryogenic conditions by free-radical copolymerization of poly[N5-(2-hydroxyethyl)-l-glutamine-stat-N5-(2-methacryloyl-oxy-ethyl)-l-glutamine] (PHEG-MA) with 2-hydroxyethyl methacrylate (HEMA) and N-propargyl methacrylamide (PrMAAm) as minor co-monomers...
December 11, 2017: Soft Matter
https://www.readbyqxmd.com/read/29226720/memantine-induces-apoptosis-and-inhibits-cell-cycle-progression-in-lncap-prostate-cancer-cells
#9
G Albayrak, E Konac, A U Dikmen, C Y Bilen
Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29224922/neurons-and-satellite-glial-cells-in-adult-rat-lumbar-dorsal-root-ganglia-express-connexin-36
#10
E Martha Pérez Armendariz, Monica Norcini, Beatriz Hernández-Tellez, Andrés Castell-Rodríguez, Cristina Coronel-Cruz, Raquel Guerrero Alquicira, Alexandra Sideris, Esperanza Recio-Pinto
Previous studies have shown that following peripheral nerve injury there was a downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord; however, it is not known whether Cx36 protein is expressed in the dorsal root ganglia (DRGs), nor if its levels are altered following peripheral nerve injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using immunohistochemistry (IHC) and immunofluorescence (IF)...
December 7, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29224892/how-glucose-glutamine-and-fatty-acid-metabolism-shape-blood-and-lymph-vessel-development
#11
REVIEW
Laure-Anne Teuwen, Vincent Geldhof, Peter Carmeliet
Recently, endothelial cell metabolism has emerged as an essential driver and regulator of both blood and lymph vessel development. Evidence rapidly builds that metabolism is not only necessary for endothelial cell function, but moreover controls several aspects of the (lymph)-angiogenic process. So far, the best-characterized metabolic pathways to have an impact on angiogenesis are glycolysis, fatty acid oxidation and glutamine metabolism. Glycolysis regulates tip cell behavior by providing ATP, fatty acid oxidation controls stalk cell proliferation by producing nucleotide biomass, and glutamine metabolism is critical for tip and stalk cell dynamics by supporting Krebs cycle anaplerosis, protein production and redox homeostasis, and links to asparagine metabolism...
December 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29224573/brain-glutamate-in-medication-free-depressed-patients-a-proton-mrs-study-at-7-tesla
#12
Beata R Godlewska, Charles Masaki, Ann L Sharpley, Philip J Cowen, Uzay E Emir
BACKGROUND: The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx...
December 11, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/29223645/amino-acid-supplements-in-critically-ill-patients
#13
REVIEW
Jan Gunst, Ilse Vanhorebeek, Steven E Thiessen, Greet Van den Berghe
Observational studies have associated a low amino acid intake with adverse outcome of critical illness. Although this finding could theoretically be explained by differences in feeding tolerance related to illness severity, guidelines have recommended to administer sufficient amounts of amino acids from early onwards in the disease course. Recently, however, several high quality randomized controlled trials have not shown benefit by early amino acid supplementation and some trials even found potential harm, thus questioning this recommendation...
December 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29222329/glutaminolysis-is-required-for-tgf-%C3%AE-1-induced-myofibroblast-differentiation-and-activation
#14
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis.  Myofibroblast differentiation is characterized by the expression of alpha-smooth muscle actin (α-SMA) and extracellular matrix (ECM) proteins, and is dependent on metabolic reprogramming.  In this study, we explored the role of glutaminolysis and metabolites of the tricarboxylic acid cycle (TCA) in supporting myofibroblast differentiation.  Glutaminolysis converts glutamine (Gln) into alpha-ketoglutarate (α-KG), a critical intermediate in the TCA cycle...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29221791/online-effects-of-transcranial-direct-current-stimulation-on-prefrontal-metabolites-in-gambling-disorder
#15
Maya Dickler, Christophe Lenglos, Emmanuelle Renauld, Francine Ferland, Richard A Edden, Jean Leblond, Shirley Fecteau
Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA...
December 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221133/endogenous-glutamine-decrease-is-associated-with-pancreatic-cancer-progression
#16
Cecilia Roux, Chiara Riganti, Sammy Ferri Borgogno, Roberta Curto, Claudia Curcio, Valeria Catanzaro, Giuseppe Digilio, Sergio Padovan, Maria Paola Puccinelli, Monica Isabello, Silvio Aime, Paola Cappello, Francesco Novelli
Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220567/the-structural-basis-of-the-histone-demethylase-kdm6b-histone-3-lysine-27-specificity
#17
Sarah Elizabeth Jones, Lars Olsen, Michael Gajhede
KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyse demethylation of di-/tri-methylated lysine on Histone 3 lysine 27 (H3K27me3/2) and play an important role in repression of developmental genes. Despite identical amino acid sequence in the immediate surroundings of H3K9me3/2 (ARKS) the enzymes do not catalyse demethylation of this general marker of repression. In order to address this question for KDM6B we used computational methods to identify H3(17-33) derived peptides with improved binding affinity, that would enable co-crystallization with the catalytic core of human KDM6B (ccKDM6B)...
December 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/29219809/the-cell-wall-of-the-filamentous-anoxygenic-phototrophic-bacterium-oscillochloris-trichoides
#18
Olga I Keppen, Ruslan N Ivanovsky, Galina M Streshinskaya, Natalia V Lebedeva, Alexander S Shashkov, Andrey S Dmitrenok, Denis S Grouzdev
The filamentous anoxygenic phototrophic bacterium Oscillochloris trichoides DG-6 has been studied, and it has been shown that there are no lipopolysaccharides on the cell surface. Fatty acids hydroxylated at the C3 position, amino sugars and phosphate-containing compounds characteristic of lipid A have also not been found. The genes encoding for proteins responsible for the synthesis of lipopolysaccharides and the genes for the transport system, usually localized in the outer membrane of Gram-negative bacteria, have not been detected in the genome...
December 8, 2017: Microbiology
https://www.readbyqxmd.com/read/29217764/radiotherapy-activated-cancer-associated-fibroblasts-promote-tumor-progression-through-paracrine-igf-1r-activation
#19
Joke Tommelein, Elly De Vlieghere, Laurine Verset, Elodie Melsens, Justine Leenders, Benedicte Descamps, Annelies Debucquoy, Christian Vanhove, Patrick Pauwels, Christian P Gespach, Anne Vral, Astrid De Boeck, Karin Haustermans, Pascal de Tullio, Wim Ceelen, Pieter Demetter, Tom Boterberg, Marc Bracke, Olivier De Wever
Preoperative radiotherapy (RT) is a mainstay in the management of rectal cancer (RC), a tumor characterized by desmoplastic stroma containing cancer-associated fibroblasts (CAF). Although CAF are abundantly present, the effects of RT to CAF and its impact on cancer cells are unknown. We evaluated the damage responses of CAF to RT and investigated changes in colorectal cancer (CRC) cell growth, transcriptome, metabolome, and kinome in response to paracrine signals emerging from irradiated CAF. RT to CAF induced DNA damage, p53 activation, cell cycle arrest, and secretion of paracrine mediators including insulin-like growth factor-1 (IGF-1)...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29217579/structural-basis-for-methylphosphonate-biosynthesis
#20
David A Born, Emily C Ulrich, Kou-San Ju, Spencer C Peck, Wilfred A van der Donk, Catherine L Drennan
Methylphosphonate synthase (MPnS) produces methylphosphonate, a metabolic precursor to methane in the upper ocean. Here, we determine a 2.35-angstrom resolution structure of MPnS and discover that it has an unusual 2-histidine-1-glutamine iron-coordinating triad. We further solve the structure of a related enzyme, hydroxyethylphosphonate dioxygenase from Streptomyces albus (SaHEPD), and find that it displays the same motif. SaHEPD can be converted into an MPnS by mutation of glutamine-adjacent residues, identifying the molecular requirements for methylphosphonate synthesis...
December 8, 2017: Science
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