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Adenosine

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https://www.readbyqxmd.com/read/28812932/celebrating-wobble-decoding-half-a-century-and-still-much-is-new
#1
Paul F Agris, Emily R Eruysal, Amithi Narendran, Ville Y P Väre, Sweta Vangaveti, Srivathsan V Ranganathan
A simple post-transcriptional modification of tRNA, deamination of adenosine to inosine at the first, or wobble, position of the anticodon, inspired Francis Crick's Wobble Hypothesis 50 years ago. Many more naturally-occurring modifications have been elucidated and continue to be discovered. The post-transcriptional modifications of tRNA's anticodon domain are the most diverse and chemically complex of any RNA modifications. Their contribution with regards to chemistry, structure and dynamics reveal individual and combined effects on tRNA function in recognition of cognate and wobble codons...
August 16, 2017: RNA Biology
https://www.readbyqxmd.com/read/28812413/unusual-retinopathy-in-a-child-with-severe-combined-immune-deficiency
#2
Christina Gerth-Kahlert, Amit Tiwari, Mathias M Hauri-Hohl, James V M Hanson, Angela Bahr, Anja Palmowski-Wolfe, Tayfun Güngör, Wolfgang Berger
We describe a case of an infant diagnosed with severe combined immune deficiency (Adenosine Deaminase (ADA), SCID) with severe retinopathy and associated low vision in both eyes at first examination. An extensive infectious work up revealed an enterovirus infection, which suggested an early infectious and severe retinopathy. Genetic causes of congenital retinitis pigmentosa/ Leber's congenital amaurosis could be excluded by whole exome sequencing.
August 16, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28811572/inhibition-of-connexin-hemichannels-alleviates-non-alcoholic-steatohepatitis-in-mice
#3
Joost Willebrords, Bruno Cogliati, Isabel Veloso Alves Pereira, Tereza Cristina da Silva, Sara Crespo Yanguas, Michaël Maes, Veronica Mollica Govoni, Andressa Lima, Daniele Aparecida Felisbino, Elke Decrock, Marina Sayuri Nogueira, Inar Alves de Castro, Isabelle Leclercq, Luc Leybaert, Robim Marcelino Rodrigues, Mathieu Vinken
While gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811127/attenuation-of-sunitinib-induced-cardiotoxicity-through-the-a3-adenosine-receptor-activation
#4
Hardip Sandhu, Samantha Cooper, Afthab Hussain, Christopher Mee, Helen Maddock
Sunitinib is an anti-cancer tyrosine kinase inhibitor associated with severe cardiotoxic adverse effects. Using rat Langendorff heart model and human acute myeloid leukemia 60 (HL60) cell line we detected the involvement of protein kinase C (PKC) α during Sunitinib-induced cardiotoxicity and the effect of Sunitinib on cancer progression. The cardioprotective and anti-cancer properties of the A3 adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were investigated...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28811090/guanosine-exerts-antiplatelet-and-antithrombotic-properties-through-an-adenosine-related-camp-pka-signaling
#5
Francisco Fuentes, Marcelo Alarcón, Lina Badimon, Manuel Fuentes, Karl-Norbert Klotz, Gemma Vilahur, Sonja Kachler, Teresa Padró, Iván Palomo, Eduardo Fuentes
BACKGROUND: Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myocardial ischemia. Platelets are critically involved in ischemic coronary events. It remains unknown, however, whether guanosine may affect platelet activation and function. We sought to investigate the potential antiplatelet and antithrombotic properties of guanosine and decipher the mechanisms behind. METHODS: We firstly assessed the effects of guanosine on platelet activation/aggregation upon stimulation with several platelet agonists including adenosine diphosphate (ADP), collagen, arachidonic acid (AA), and TRAP-6...
August 7, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28810562/anti-depressant-like-effects-of-jieyu-chufan-capsules-in-a-mouse-model-of-unpredictable-chronic-mild-stress
#6
Hui Zhao, Bingyu Liang, Linjie Yu, Yun Xu
Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810234/electrochemical-aptamer-based-nanosensor-fabricated-on-single-au-nanowire-electrodes-for-adenosine-triphosphate-assay
#7
Dongmei Wang, Xiaoqing Xiao, Shen Xu, Yong Liu, Yongxin Li
In this work, single Au nanowire electrodes (AuNWEs) were fabricated by laser-assisted pulling/hydrofluoric acid (HF) etching process, which then were characterized by transmission electron microscopy (TEM), electrochemical method and finite-element simulation. The as-prepared single AuNWEs were used to construct electrochemical aptamer-based nanosensors (E-AB nanosensors) based on the formation of Au-S bond that duplex DNA tagged with methylene blue (MB) was modified on the surface of electrode. In the presence of adenosine triphosphate (ATP), the MB-labeled aptamer dissociated from the duplex DNA due to the strong specific affinity between aptamer and target, which lead to the reduction of MB electrochemical signals...
August 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28809765/cyclin-dependent-kinase-5-modulates-the-p2x2a-receptor-channel-gating-through-phosphorylation-of-c-terminal-threonine-372
#8
Claudio Coddou, Rodrigo Sandoval, Patricio Castro, Pablo Lazcano, Maria José Hevia, Milos Rokic, Bradford Hall, Anita Terse, Christian Gonzalez-Billault, Ashok B Kulkarni, Stanko S Stojilkovic, Elias Utreras
The purinergic P2X2 receptor (P2X2R) is an adenosine triphosphate-gated ion channel widely expressed in the nervous system. Here, we identified a putative cyclin-dependent kinase 5 (Cdk5) phosphorylation site in the full-size variant P2X2aR (TPKH), which is absent in the splice variant P2X2bR. We therefore investigated the effects of Cdk5 and its neuronal activator, p35, on P2X2aR function. We found an interaction between P2X2aR and Cdk5/p35 by co-immunofluorescence and co-immunoprecipitation in HEK293 cells...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28809723/nitroglycerin-derived-pd-pa-for-the-assessment-of-intermediate-coronary-lesions
#9
Zeev Israeli, Rodrigo Bagur, Dorian Murariu, Sabrina Wall, Mistre Alemayehu, Yasir Parviz, Pantelis Diamantouros, Shahar Lavi
OBJECTIVES: To assess the predictive value of Pd/Pa after nitroglycerin administration (Pd/Pa[N]) as compared with standard fractional flow reserve (FFR). METHODS: Consecutive patients with intermediate coronary lesions assessed by FFR between January 2014 and October 2015 were included. We measured Pd/Pa at baseline, Pd/Pa(N), and Pd/Pa after incremental doses of intracoronary adenosine. RESULTS: A total of 134 patients (27% females; mean age, 65 years) were included...
August 15, 2017: Journal of Invasive Cardiology
https://www.readbyqxmd.com/read/28809392/mettl3-mediated-m-6-a-regulates-spermatogonial-differentiation-and-meiosis-initiation
#10
Kai Xu, Ying Yang, Gui-Hai Feng, Bao-Fa Sun, Jun-Qing Chen, Yu-Fei Li, Yu-Sheng Chen, Xin-Xin Zhang, Chen-Xin Wang, Li-Yuan Jiang, Chao Liu, Ze-Yu Zhang, Xiu-Jie Wang, Qi Zhou, Yun-Gui Yang, Wei Li
METTL3 catalyzes the formation of N(6)-methyl-adenosine (m(6)A) which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we generated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and spermatogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and m(6)A profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing...
August 15, 2017: Cell Research
https://www.readbyqxmd.com/read/28808968/cgamp-quantification-in-virus-infected-human-monocyte-derived-cells-by-hplc-coupled-tandem-mass-spectrometry
#11
Jennifer Paijo, Volkhard Kaever, Ulrich Kalinke
Upon virus infection, cells of the innate immune system such as dendritic cells and macrophages can mount type I interferon (IFN-I) responses that restrict viral dissemination. To inform host cells of virus infection, detection of cytosolic DNA is one important mechanism. Inappropriate sensing of endogenous DNA and subsequent induction of IFN-I responses can also cause autoimmunity, highlighting the need to tightly regulate DNA sensing. The cyclic GMP-AMP synthase (cGAS) was recently identified to be the major sensor of cytosolic DNA that triggers IFN-I expression...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808842/colonic-motor-dysfunctions-in-a-mouse-model-of-high-fat-diet-induced-obesity-an-involvement-of-a2b-adenosine-receptors
#12
Luca Antonioli, Carolina Pellegrini, Matteo Fornai, Erika Tirotta, Daniela Gentile, Laura Benvenuti, Maria Cecilia Giron, Valentina Caputi, Ilaria Marsilio, Genny Orso, Nunzia Bernardini, Cristina Segnani, Chiara Ippolito, Balázs Csóka, Zoltán H Németh, György Haskó, Carmelo Scarpignato, Corrado Blandizzi, Rocchina Colucci
Adenosine A2B receptors (A2BR) regulate several enteric functions. However, their implication in the pathophysiology of intestinal dysmotility associated with high-fat diet (HFD)-induced obesity has not been elucidated. We investigated the expression of A2BR in mouse colon and their role in the mechanisms underlying the development of enteric dysmotility associated with obesity. Wild-type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD; 18% kcal from fat) for 8 weeks. Colonic A2BR localization was examined by immunofluorescence...
August 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28808132/defining-electron-bifurcation-in-the-electron-transferring-flavoprotein-family
#13
Amaya M Garcia Costas, Saroj Poudel, Anne-Frances Miller, Gerrit J Schut, Rhesa N Ledbetter, Kathryn R Fixen, Lance C Seefeldt, Michael W W Adams, Caroline S Harwood, Eric S Boyd, John W Peters
Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low and high potential electrons. It is the third recognized form of energy conservation in biology and has recently been described in select electron transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via ETF quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer as well as a non-redox active adenosine monophosphate (AMP)...
August 14, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28808129/gene-duplication-in-pseudomonas-aeruginosa-improves-growth-on-adenosine
#14
Jean-Paul Toussaint, Anna Farrell-Sherman, Tamar Perla Feldman, Nicole E Smalley, Amy L Schaefer, E Peter Greenberg, Ajai A Dandekar
The laboratory strain of Pseudomonas aeruginosa, PAO1, activates genes for catabolism of adenosine using quorum sensing (QS). However, this strain is not well-adapted for growth on adenosine, with doubling times greater than 40 h. We previously showed that when PAO1 is grown on adenosine and casein, variants emerge that grow rapidly on adenosine. To understand the mechanism by which this adaptation occurs, we performed whole-genome sequencing of five isolates evolved for rapid growth on adenosine. All five genomes had a gene duplication-amplification (GDA) event covering several genes, including the quorum-regulated nucleoside hydrolase, nuh, and an adenine deaminase encoded by PA0148...
August 14, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28808024/structural-and-functional-studies-of-pyruvate-carboxylase-regulation-by-cyclic-di-amp-in-lactic-acid-bacteria
#15
Philip H Choi, Thu Minh Ngoc Vu, Huong Thi Pham, Joshua J Woodward, Mark S Turner, Liang Tong
Cyclic di-3',5'-adenosine monophosphate (c-di-AMP) is a broadly conserved bacterial second messenger that has been implicated in a wide range of cellular processes. Our earlier studies showed that c-di-AMP regulates central metabolism in Listeria monocytogenes by inhibiting its pyruvate carboxylase (LmPC), a biotin-dependent enzyme with biotin carboxylase (BC) and carboxyltransferase (CT) activities. We report here structural, biochemical, and functional studies on the inhibition of Lactococcus lactis PC (LlPC) by c-di-AMP...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807514/highly-selective-activation-of-heat-shock-protein-70-by-allosteric-regulation-provides-an-insight-into-efficient-neuroinflammation-inhibition
#16
Li-Chao Wang, Li-Xi Liao, Hai-Ning Lv, Dan Liu, Wei Dong, Jian Zhu, Jin-Feng Chen, Meng-Ling Shi, Ge Fu, Xiao-Min Song, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu
Heat shock protein 70 (Hsp70) is widely involved in immune disorders, making it as an attractive drug target for inflammation diseases. Nonselective induction of Hsp70 upregulation for inflammation therapy could cause extensive interference in inflammation-unrelated protein functions, potentially resulting in side effects. Nevertheless, direct pharmacological activation of Hsp70 via targeting specific functional amino acid residue may provide an insight into precise Hsp70 function regulation and a more satisfactory treatment effect for inflammation, which has not been extensively focused...
August 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28807491/adenosine-a2a-receptor-signaling-affects-il-21-il-22-cytokines-and-gata3-t-bet-transcription-factor-expression-in-cd4-t-cells-from-a-btbr-t-itpr3tf-j-mouse-model-of-autism
#17
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Mashal M Almutairi, Sabry M Attia
Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T(+) Itpr3tf/J (BTBR) mice are used as a model for autism, as they exhibit social deficits, communication deficits, and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral, inflammatory, immune, and neurological disorders...
August 9, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28807217/adenosine-triphosphate-as-a-molecular-mediator-of-the-vascular-response-to-injury
#18
Christy M Guth, Weifung Luo, Olukemi Jolayemi, Kalyan S Chadalavada, Padmini Komalavilas, Joyce Cheung-Flynn, Colleen M Brophy
BACKGROUND: Human saphenous veins used for arterial bypass undergo stretch injury at the time of harvest and preimplant preparation. Vascular injury promotes intimal hyperplasia, the leading cause of graft failure, but the molecular events leading to this response are largely unknown. This study investigated adenosine triphosphate (ATP) as a potential molecular mediator in the vascular response to stretch injury, and the downstream effects of the purinergic receptor, P2X7R, and p38 MAPK activation...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28806651/changes-in-the-process-performance-sludge-production-and-microbial-activity-in-an-activated-sludge-reactor-with-addition-of-a-metabolic-uncoupler-under-different-operating-conditions
#19
E Ferrer-Polonio, J Fernández-Navarro, J L Alonso-Molina, I Amorós-Muñoz, A Bes-Piá, J A Mendoza-Roca
Sludge production in wastewater treatment plants is nowadays a big concern due to the high produced amounts and their characteristics. Consequently, the study of techniques that reduce the sludge generation in wastewater treatment plants is becoming of great importance. In this work, four laboratory sequencing batch reactors (SBRs), which treated municipal wastewater, were operated to study the effect of adding the metabolic uncoupler 3,3',4',5-tetrachlorosalicylanilide (TCS) on the sludge reduction, the SBRs performance and the microbial hydrolytic enzymatic activities (MHEA)...
August 11, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28806076/structure-affinity-relationships-and-structure-kinetics-relationships-of-pyrido-2-1-f-purine-2-4-dione-derivatives-as-human-adenosine-a3-receptor-antagonists
#20
Lizi Xia, Wessel A C Burger, Jacobus P D van Veldhoven, Boaz J Kuiper, Tirsa T van Duijl, Eelke B Lenselink, Ellen Paasman, Laura H Heitman, Adriaan P IJzerman
We expanded on a series of pyrido[2,1-f]purine-2,4-dione derivatives as human adenosine A3 receptor (hA3R) antagonists to determine their kinetic profiles and affinities. Many compounds showed high affinities and a diverse range of kinetic profiles. We found hA3R antagonists with very short residence time at the receptor (RT of 2.2 min for 5) and much longer RTs (e.g. 376 min for 27, or 391 min for 31). Two representative antagonists (5 and 27) were tested in [(35)S]GTPγS binding assays, and their RTs appeared correlated to their (in)surmountable antagonism...
August 14, 2017: Journal of Medicinal Chemistry
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