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https://www.readbyqxmd.com/read/28543779/inosine-can-increase-dna-s-susceptibility-to-photo-oxidation-by-a-ru-ii-complex-due-to-structural-change-in-the-minor-groove
#1
John M Kelly, Paraic Keane, James Hall, Fergus Poynton, Bjorn Poulsen, Sarah Gurung, Ian Clark, Igor Sazanovich, Michael Towrie, Thorfinnur Gunnlaugsson, Susan Quinn, Christine Cardin
Key to the development of DNA-targeting phototherapeutic drugs is determining the interplay between the photoactivity of the drug and its binding preference for a target sequence. For the photo-oxidising lambda-[Ru(TAP)2(dppz)]2+ (Ʌ-1) complex bound to either d{T1C2G3G4C5G6C7C8G9A10}2 (G9) or d{TCGGCGCCIA}2 (I9), the X-ray crystal structures shows the dppz intercalated at the terminal T1C2;G9A10 step or T1C2;I9A10 step. Thus substitution of the G9 nucleobase by inosine does not affect intercalation in the solid state although with I9 the dppz is more deeply inserted...
May 25, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28543275/the-role-of-itpa-and-ribavirin-transporter-genes-polymorphisms-in-prediction-of-ribavirin-induced-anemia-in-chronic-hepatitis-c-egyptian-patients
#2
Ehab S El Desoky, Alaa T Abdelhafez, Jessica Cusato, Sherif I Kamel, Abeer M R Hussein, Amedeo De Nicolo, Giovanni Di Perri, Antonio D'Avolio
Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV-induced anemia among Egyptians with chronic hepatitis C (CHC). Genotyping of 3 ITPA gene variants and 2 variants of RBV transporter genes has been performed in 123 patients under pegylated interferon-α/ribavirin treatment. The baseline hemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anemia at 4, 8 and 12 weeks of RBV therapy. In addition, ITPA rs7270101 AC/CC and age predicted anemia after 12 weeks of therapy...
May 24, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28542129/adar1-mediated-3-utr-editing-and-expression-control-of-antiapoptosis-genes-fine-tunes-cellular-apoptosis-response
#3
Chang-Ching Yang, Yi-Tung Chen, Yi-Feng Chang, Hsuan Liu, Yu-Ping Kuo, Chieh-Tien Shih, Wei-Chao Liao, Hui-Wen Chen, Wen-Sy Tsai, Bertrand Chin-Ming Tan
Adenosine-to-inosine RNA editing constitutes a crucial component of the cellular transcriptome and critically underpins organism survival and development. While recent high-throughput approaches have provided comprehensive documentation of the RNA editome, its functional output remains mostly unresolved, particularly for events in the non-coding regions. Gene ontology analysis of the known RNA editing targets unveiled a preponderance of genes related to apoptosis regulation, among which proto-oncogenes XIAP and MDM2 encode two the most abundantly edited transcripts...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28517175/comparison-of-the-human-a2a-adenosine-receptor-recognition-by-adenosine-and-inosine-new-insights-from-supervised-molecular-dynamics-simulations
#4
Giuseppe Deganutti, Ajith Welihinda, Stefano Moro
Adenosine deaminase converts adenosine to inosine. Differently by adenosine, modest attention has been dedicated to the physiological roles of inosine. Nevertheless, recent studies demonstrate that inosine has neuroprotective, cardioprotective immunomodulatory, and antidepressive effects. It has been recently reported by Welihinda and collaborators that inosine is a less potent agonist than adenosine at the A2A AR. To better depict the differences in receptor recognition mechanism of both adenosine and inosine, in this work supervised molecular dynamics (SuMD) simulations have been performed and analyzed...
May 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28513806/increased-activity-of-vascular-adenosine-deaminase-in-atherosclerosis-and-therapeutic-potential-of-its-inhibition
#5
Barbara Kutryb-Zajac, Lukasz Mateuszuk, Paulina Zukowska, Agnieszka Jasztal, Magdalena A Zabielska, Marta Toczek, Patrycja Jablonska, Agnieszka Zakrzewska, Barbara Sitek, Jan Rogowski, Romuald Lango, Ewa M Slominska, Stefan Chlopicki, Ryszard T Smolenski
Aims: Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis...
November 1, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/28509906/therapeutic-efficacy-of-atypical-antipsychotic-drugs-by-targeting-multiple-stress-related-metabolic-pathways
#6
H L Cai, P Jiang, Q Y Tan, R L Dang, M M Tang, Y Xue, Y Deng, B K Zhang, P F Fang, P Xu, D X Xiang, H D Li, J K Yao
Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28502927/mizoribine-synchronized-methotrexate-therapy-should-be-considered-when-treating-rheumatoid-arthritis-patients-with-an-inadequate-response-to-various-combination-therapies
#7
Keigo Ikeda, Kozo Watanabe, Takuya Hirai, Kana Tanji, Tomoko Miyashita, Shihoko Nakajima, Kaori Uomori, Shinji Morimoto, Kenji Takamori, Hideoki Ogawa, Yoshinari Takasaki, Iwao Sekigawa
Objective The objective of this study was to confirm the efficacy of low-dose mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, as part of synchronized methotrexate (MTX) therapy for rheumatoid arthritis (RA) patients with an inadequate response to various combination therapies of MTX, other synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs. Methods Low-dose MZR was administered to 56 uncontrolled RA patients being treated with MTX and various biological DMARDs...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28502110/a-novel-frameshift-mutation-of-the-adar1-gene-in-a-chinese-patient-with-dyschromatosis-symmetrica-hereditaria-and-the-dermoscopic-features
#8
Cheng Chi, Yixin Luo, Jie Liu
Dyschromatosis symmetrica hereditaria (DSH), which characterized by hyper- or hypopigmented macules on the dorsal aspect of distal extremities and freckle-like macules on the face, is a rare pigmented genodermatosis that usually restricted to the skin. Generally, DSH is considered autosomal dominant, and adenosine deaminase acting on the RNA-1 (ADAR1) gene is one of the responsible genes [1]. ADAR catalyses adenosine-to-inosine (A-to-I) editing of dsRNA substrates, which plays an important role in posttranscriptional regulatory processes...
May 14, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28496447/inosine-released-from-dying-or-dead-cells-stimulates-cell-proliferation-via-adenosine-receptors
#9
Jin Chen, Ricardo A Chaurio, Christian Maueröder, Anja Derer, Manfred Rauh, Andriy Kost, Yi Liu, Xianming Mo, Axel Hueber, Rostyslav Bilyy, Martin Herrmann, Yi Zhao, Luis E Muñoz
INTRODUCTION: Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells. METHODS: Cultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS) in the presence of dead and dying cells, their supernatants (SNs), or purified agonists and antagonists were used to evaluate the stimulation of proliferation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28486975/evidence-for-transcriptome-wide-rna-editing-among-sus-scrofa-pre-1-sine-elements
#10
Scott A Funkhouser, Juan P Steibel, Ronald O Bates, Nancy E Raney, Darius Schenk, Catherine W Ernst
BACKGROUND: RNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome. RESULTS: Here, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig...
May 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28484188/c-to-u-editing-and-site-directed-rna-editing-for-the-correction-of-genetic-mutations
#11
Luyen Thi Vu, Toshifumi Tsukahara
Cytidine to uridine (C-to-U) editing is one type of substitutional RNA editing. It occurs in both mammals and plants. The molecular mechanism of C-to-U editing involves the hydrolytic deamination of a cytosine to a uracil base. C-to-U editing is mediated by RNA-specific cytidine deaminases and several complementation factors, which have not been completely identified. Here, we review recent findings related to the regulation and enzymatic basis of C-to-U RNA editing. More importantly, when C-to-U editing occurs in coding regions, it has the power to reprogram genetic information on the RNA level, therefore it has great potential for applications in transcript repair (diseases related to thymidine to cytidine (T>C) or adenosine to guanosine (A>G) point mutations)...
May 8, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28480960/itpa-gene-polymorphism-94c-a-effects-on-ribavirin-induced-anemia-during-therapy-in-egyptian-patients-with-chronic-hepatitis-c
#12
Maissa El Raziky, Naglaa Ali Zayed, Amin Abdel Baki, Shimaa Afify Mansour, Rasha Mohamad Hosny Shahin
PROBLEM: Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)-induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction and treatment response in hepatitis C virus (HCV)-infected patients. METHOD OF STUDY: This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated-interferon (PEG-INF) /RBV therapy...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28473819/metabolic-profiles-in-cell-lines-infected-with-classical-swine-fever-virus
#13
Hongchao Gou, Mingqiu Zhao, Jin Yuan, Hailuan Xu, Hongxing Ding, Jinding Chen
Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV) and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF). In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS) to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC) = -1...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28464292/rnai-mediated-gene-silencing-of-itpa-using-a-targeted-nanocarrier-apoptosis-induction-in-skbr3-cancer-cells
#14
Fahimeh Charbgoo, Mehrdad Behmanesh, Maryam Nikkhah, Eric G Kane
A pure nucleotide pool is required for high-fidelity DNA replication and prevention of carcinogenesis in living cells. Human inosine triphosphatase (ITPase), encoded by the ITPA gene, plays a critical role in maintaining the purity of the cellular nucleotide pool by excluding nucleotides that enhance mutagenesis. ITPase is a nucleoside triphosphate pyrophosphatase that hydrolyzes the non-canonical nucleotides inosine triphosphate (ITP) and xanthine triphosphate (XTP). The monophosphate products of ITPase reactions are subsequently excluded from the nucleotide pool and the improper substitution of ITP and XTP into DNA and RNA is prevented...
May 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28453984/functional-and-genetic-evidence-that-nucleoside-transport-is-highly-conserved-in-leishmania-species-implications-for-pyrimidine-based-chemotherapy
#15
Khalid J H Alzahrani, Juma A M Ali, Anthonius A Eze, Wan Limm Looi, Daniel N A Tagoe, Darren J Creek, Michael P Barrett, Harry P de Koning
Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1)...
April 20, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28453786/a-to-i-rna-editing-in-the-earliest-diverging-eumetazoan-phyla
#16
Hagit T Porath, Amos Schaffer, Paulina Kaniewska, Shahar Alon, Eli Eisenberg, Joshua Rosenthal, Erez Y Levanon, Oren Levy
The highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze the editing of mRNA transcripts by the deamination of adenosines to inosines. This type of editing has two general outcomes: site specific editing, which frequently leads to recoding, and clustered editing, which is usually found in transcribed genomic repeats. Here, for the first time we looked for both editing of isolated sites and clustered, non-specific sites in a basal metazoan, the coral Acropora millepora during spawning event, in order to reveal its editing pattern...
April 8, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28453010/effect-of-nucleobase-change-on-cytosine-deamination-through-dna-photo-cross-linking-reaction-via-3-cyanovinylcarbazole-nucleoside
#17
Siddhant Sethi, Minako Ooe, Takashi Sakamoto, Kenzo Fujimoto
Photo-chemical deamination of cytosine using 3-cyanovinylcarbazole nucleoside ((CNV)K) mediated photo-cross-linking is a technique for site-directed mutagenesis. Using this technique in vivo requires the elimination of a high-temperature incubation step; instead, incubation should be carried out under physiological conditions. To improve the reactivity of (CNV)K mediated photo-cross-link induced deamination of cytosine under physiological conditions, an evaluation of base pairing in cytosine was carried out with respect to its deamination...
April 28, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28448526/human-alkaline-phosphatase-dephosphorylates-microbial-products-and-is-elevated-in-preterm-neonates-with-a-history-of-late-onset-sepsis
#18
Matthew Pettengill, Juan D Matute, Megan Tresenriter, Julie Hibbert, David Burgner, Peter Richmond, José Luis Millán, Al Ozonoff, Tobias Strunk, Andrew Currie, Ofer Levy
BACKGROUND: A host defense function for Alkaline phosphatases (ALPs) is suggested by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide (endotoxin) in animal models in vivo and the elevation of ALP activity following treatment of human cells with inflammatory stimuli in vitro. However the activity of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on lipopolysaccharide and other microbial products has not been assessed, nor has its expression been studied in preterm newborns, a vulnerable population at high risk of sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/28436945/adar1-controls-apoptosis-of-stressed-cells-by-inhibiting-staufen1-mediated-mrna-decay
#19
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28411194/systematic-characterization-of-a-to-i-rna-editing-hotspots-in-micrornas-across-human-cancers
#20
Yumeng Wang, Xiaoyan Xu, Shuangxing Yu, Kang Jin Kang, Zhicheng Zhou, Leng Han, Yiu Huen Tsang, Jun Li, Hu Chen, Lingegowda S Mangala, Yuan Yuan, A Karina Eterovic, Yiling Lu, Anil K Sood, Kenneth L Scott, Gordon B Mills, Han Liang
RNA editing, a widespread posttranscriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here we systematically characterized the miRNA editing profiles of 8,595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines...
April 14, 2017: Genome Research
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