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https://www.readbyqxmd.com/read/29329872/development-and-validation-of-a-hilic-uv-method-for-the-determination-of-nucleotides-in-fish-samples
#1
Maria Logotheti, Konstantina Theochari, Marios Kostakis, Ioannis N Pasias, Nikolaos S Thomaidis
The aim of this work was the development of a simple, novel and accurate method for the determination of adenosine triphosphate (ATP) and its first five catabolites: adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine (Ino) and hypoxanthine (Hx), in fish tissue, based on hydrophilic interaction liquid chromatography (HILIC). For this purpose, a stationary phase for polar and hydrophilic compounds (ZIC-pHILIC) was used. The effect of different chromatographic parameters and the molecular mechanism based on the van't Hoff plot were examined...
May 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29329318/erythrocyte-inosine-triphosphatase-activity-a-potential-biomarker-for-adverse-events-during-combination-antiretroviral-therapy-for-hiv
#2
N Chantal Peltenburg, Jörgen Bierau, Jaap A Bakker, Jolanda A Schippers, Selwyn H Lowe, Aimée D C Paulussen, Bianca J C van den Bosch, Mathie P G Leers, Bettina E Hansen, Annelies Verbon
The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal...
2018: PloS One
https://www.readbyqxmd.com/read/29327413/itpa-activity-in-children-treated-by-azathioprine-relationship-to-the-occurrence-of-adverse-drug-reactions-and-inflammatory-response
#3
Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin, Alain Lachaux, Roselyne Boulieu
Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological disease such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reaction (ADRs) and drug response is observed. This study investigated 1) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, 2) the relationship between ITPA activity and the inflammatory activity observed in children with IBD...
January 11, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29323188/a-tet-off-gene-expression-system-for-validation-of-antifungal-drug-targets-in-a-murine-invasive-pulmonary-aspergillosis-model
#4
Yutian Peng, Hua Zhang, Min Xu, Man-Wah Tan
Aspergillus fumigatus is one of the major causes of invasive pulmonary aspergillosis in immunocompromised patients. Novel antifungal therapy is in urgent need due to emerging resistance and adverse toxicity of current antifungal drugs. Gene products that are essential for Aspergillus viability during infection are attractive drug targets. To characterize these genes in vivo we developed a Tet-Off gene expression system in A. fumigatus, whereby the administration of doxycycline resulted in down regulation of the gene whose expression is under the control of the Tet-Off promoter...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310578/a-to-i-rna-editing-in-the-rat-brain-is-age-dependent-region-specific-and-sensitive-to-environmental-stress-across-generations
#5
Hiba Zaidan, Gokul Ramaswami, Yaela N Golumbic, Noa Sher, Assaf Malik, Michal Barak, Dalia Galiani, Nava Dekel, Jin B Li, Inna Gaisler-Salomon
BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats...
January 8, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29308550/mycophenolic-acid-induces-differentiation-of-toxoplasma-gondii-rh-strain-tachyzoites-into-bradyzoites-and-formation-of-cyst-like-structure-in-vitro
#6
Kitzia N Castro-Elizalde, Pedro Hernández-Contreras, Carlos J Ramírez-Flores, Sirenia González-Pozos, Carmen T Gómez de León, Mónica Mondragón-Castelán, Ricardo Mondragón-Flores
The biochemical and structural changes that occur during the conversion of Toxoplasma gondii tachyzoites to bradyzoites and the formation of tissue cyst are not well understood. Maintaining cells infected with T. gondii type II and III strains under stress conditions induces the tachyzoite-bradyzoite in vitro differentiation, along with the formation of cyst-like structures. However, due to the long exposure to such conditions required to induce the differentiation, the severe damages in the host cell and the low encystation frequency, it has been difficult to dissect in more detail these processes...
January 8, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29306799/purine-salvage-in-plants
#7
REVIEW
Hiroshi Ashihara, Claudio Stasolla, Tatsuhito Fujimura, Alan Crozier
Purine bases and nucleosides are produced by turnover of nucleotides and nucleic acids as well as from some cellular metabolic pathways. Adenosine released from the S-adenosyl-L-methionine cycle is linked to many methyltransferase reactions, such as the biosynthesis of caffeine and glycine betaine. Adenine is produced by the methionine cycles, which is related to other biosynthesis pathways, such those for the production of ethylene, nicotianamine and polyamines. These purine compounds are recycled for nucleotide biosynthesis by so-called "salvage pathways"...
January 4, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29305710/ecto-5-nucleotidase-cd73-contributes-to-the-radiosensitivity-of-t24-human-bladder-cancer-cell-line
#8
Fabrícia Dietrich, Fabrício Figueiró, Eduardo Cremonese Filippi-Chiela, Angélica Regina Cappellari, Liliana Rockenbach, Alain Tremblay, Patrícia Boni de Paula, Rafael Roesler, Aroldo Braga Filho, Jean Sévigny, Fernanda Bueno Morrone, Ana Maria Oliveira Battastini
PURPOSE: Trimodal therapy is a reasonable bladder-preserving option to radical cystectomy. However, many tumors are radioresistive. In this sense, the identification of new prognostic and predictive biomarkers that allow the selection of patients with better responses to radiation therapy would improve outcomes. With the aim of using ecto-5'-nucleotidase/CD73 as a predictive biomarker, the role of this enzyme in the context of radiotherapy in T24 human bladder cancer cell line was investigated...
January 5, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29304330/n6-methyladenosines-modulate-a-to-i-rna-editing
#9
Jian-Feng Xiang, Qin Yang, Chu-Xiao Liu, Man Wu, Ling-Ling Chen, Li Yang
N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) editing are two of the most abundant RNA modifications, both at adenosines. Yet, the interaction of these two types of adenosine modifications is largely unknown. Here we show a global A-to-I difference between m6A-positive and m6A-negative RNA populations. Both the presence and extent of A-to-I sites in m6A-negative RNA transcripts suggest a negative correlation between m6A and A-to-I. Suppression of m6A-catalyzing enzymes results in global A-to-I RNA editing changes...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29285933/qm-mm-and-mm-md-simulations-on-the-pyrimidine-specific-nucleoside-hydrolase-a-comprehensive-understanding-toward-enzymatic-hydrolysis-of-uridine
#10
Fangfang Fan, Nan-Hao Chen, Yong-Heng Wang, Ruibo Wu, Zexing Cao
The pyrimidine-specific nucleoside hydrolase Yeik (CU-NH) from Escherichia coli cleaves the N-glycosidic bond of uridine and cytidine with a 102~104-fold faster than that of purine nucleoside substrates such as inosine. Such remarkable substrate specificity and the plausible hydrolytic mechanisms of uridine have been explored by using QM/MM and MM MD simulations. The present calculations show that the relatively stronger hydrogen bond interactions between uridine and the active-site residues Gln227 and Tyr231 in CU-NH play an important role in enhancing the substrate binding and thus promoting the N-glycosidic bond cleavage, in comparison with inosine...
December 29, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29285876/metabolomic-analysis-of-92-pulmonary-embolism-patients-from-a-nested-case-control-study-identifies-metabolites-associated-with-adverse-clinical-outcomes
#11
O A Zeleznik, E M Poole, S Lindstrom, P Kraft, A Van Hylckama Vlieg, J A Lasky-Su, L B Harrington, K Hagan, J Kim, B A Parry, N Giordano, C Kabrhel
BACKGROUND: Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. OBJECTIVES: To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study...
December 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29284691/a-to-i-editing-of-microrna-487b-alters-target-gene-selection-after-ischemia-and-promotes-neovascularization
#12
Reginald V van der Kwast, Eva van Ingen, Laura Parma, Hendrika A Peters, Paul H Quax, A Y Nossent
Rationale: Adenosine-to-inosine (A-to-I) editing of microRNAs has the potential to cause a shift in target-site selection. 2'-O-ribose-methylation (2'OMe) of adenosine residues however, has been shown to inhibit A-to-I-editing. Objective: To investigate whether angiomiR miR487b is subject to A-to-I-editing and/or 2'OMe during neovascularization. Methods and Results: cDNA was prepared from C57BL/6-mice subjected to hindlimb ischemia. Using Sanger-sequencing and endonuclease digestion, we identified and validated A-to-I-editing of the miR487b seed-sequence...
December 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/29283068/influence-of-genetic-polymorphisms-on-mycophenolic-acid-pharmacokinetics-and-patient-outcomes-in-renal-transplantation
#13
Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu, Ji-Fu Wei
Mycophenolic acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA, involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and others...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29281722/cortical-representation-of-different-taste-modalities-on-the-gustatory-cortex-a-pilot-study
#14
Anna Prinster, Elena Cantone, Viviana Verlezza, Mario Magliulo, Giovanni Sarnelli, Maurizio Iengo, Rosario Cuomo, Francesco Di Salle, Fabrizio Esposito
BACKGROUND: Right insular cortex is involved in taste discrimination, but its functional organization is still poorly known. In general, sensory cortices represent the spatial prevalence of relevant features for each sensory modality (visual, auditory, somatosensory) in an ordered way across the cortical space. Following this analogy, we hypothesized that primary taste cortex is organized in similar ordered way in response to six tastes with known receptorial mechanisms (sweet, bitter, sour, salt, umami, CO2)...
2017: PloS One
https://www.readbyqxmd.com/read/29280160/when-micrornas-meet-rna-editing-in-cancer-a-nucleotide-change-can-make-a-difference
#15
Yumeng Wang, Han Liang
RNA editing is a major post-transcriptional mechanism that changes specific nucleotides at the RNA level. The most common RNA editing type in humans is adenosine (A) to inosine (I) editing, which is mediated by ADAR enzymes. RNA editing events can not only change amino acids in proteins, but also affect the functions of non-coding RNAs such as miRNAs. Recent studies have characterized thousands of miRNA RNA editing events across different cancer types. Importantly, individual cases of miRNA editing have been reported to play a role in cancer development...
December 27, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29278490/application-of-a-deep-neural-network-to-metabolomics-studies-and-its-performance-in-determining-important-variables
#16
Yasuhiro Date, Jun Kikuchi
Deep neural networks (DNNs), which are kinds of the machine learning approaches, are powerful tools for analyzing big sets of data derived from biological and environmental systems. However, DNNs are not applicable to metabolomics studies because they have difficulty in identifying contribution factors, e.g., biomarkers, in constructed classification and regression models. In this paper, we describe an improved DNN-based analytical approach that incorporates an importance estimation for each variable using a mean decrease accuracy (MDA) calculation, which is based on a permutation algorithm; this approach is called DNN-MDA...
December 26, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29273356/global-transcriptome-analysis-of-rna-abundance-regulation-by-adar-in-lung-adenocarcinoma
#17
Michael F Sharpnack, Bin Chen, Dvir Aran, Idit Kosti, Douglas D Sharpnack, David P Carbone, Parag Mallick, Kun Huang
Despite tremendous advances in targeted therapies against lung adenocarcinoma, the majority of patients do not benefit from personalized treatments. A deeper understanding of potential therapeutic targets is crucial to increase the survival of patients. One promising target, ADAR, is amplified in 13% of lung adenocarcinomas and in-vitro studies have demonstrated the potential of its therapeutic inhibition to inhibit tumor growth. ADAR edits millions of adenosines to inosines within the transcriptome, and while previous studies of ADAR in cancer have solely focused on protein-coding edits, >99% of edits occur in non-protein coding regions...
December 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29261720/a-mutant-of-phosphomannomutase1-retains-full-enzymatic-activity-but-is-not-activated-by-imp-possible-implications-for-the-disease-pmm2-cdg
#18
Valentina Citro, Chiara Cimmaruta, Ludovica Liguori, Gaetano Viscido, Maria Vittoria Cubellis, Giuseppina Andreotti
The most frequent disorder of glycosylation, PMM2-CDG, is caused by a deficiency of phosphomannomutase activity. In humans two paralogous enzymes exist, both of them require mannose 1,6-bis-phosphate or glucose 1,6-bis-phosphate as activators, but only phospho-mannomutase1 hydrolyzes bis-phosphate hexoses. Mutations in the gene encoding phosphomannomutase2 are responsible for PMM2-CDG. Although not directly causative of the disease, the role of the paralogous enzyme in the disease should be clarified. Phosphomannomutase1 could have a beneficial effect, contributing to mannose 6-phosphate isomerization, or a detrimental effect, hydrolyzing the bis-phosphate hexose activator...
2017: PloS One
https://www.readbyqxmd.com/read/29246629/one-year-safety-and-efficacy-of-inosine-to-increase-the-serum-urate-level-for-patients-with-parkinson-s-disease-in-japan
#19
Hirotaka Iwaki, Rina Ando, Noriyuki Miyaue, Satoshi Tada, Tomoaki Tsujii, Hayato Yabe, Noriko Nishikawa, Masahiro Nagai, Masahiro Nomoto
BACKGROUND: Epidemiological studies have repeatedly reported that increased serum urate level is associated with a slower progress of Parkinson's disease (PD). The urate precursor, inosine, raises the serum urate level and is therefore a candidate for a disease modifying treatment. However, an elevated serum urate level is a risk factor for gout, urolithiasis, and cardiovascular diseases. Although there have been previous clinical studies, the use of inosine in a clinical setting is still limited, and its safety is unclear, especially in an Asian population...
December 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29246230/bifunctional-enzyme-atic-promotes-propagation-of-hepatocellular-carcinoma-by-regulating-ampk-mtor-s6%C3%A2-k1-signaling
#20
Minjing Li, Changzhu Jin, Maolei Xu, Ling Zhou, Defang Li, Yancun Yin
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. To effectively treat HCC, new molecular targets and therapeutic approaches must be identified. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate (IMP) cyclohydrolase (ATIC), a bifunctional protein enzyme, catalyzes the last two steps of the de novo purine biosynthetic pathway. Whether ATIC contributes to cancer development remains unclear. METHODS: ATIC mRNA levels in different types of human HCC samples or normal tissues were determined from Gene Expression across Normal and Tumor tissue (GENT) database...
December 16, 2017: Cell Communication and Signaling: CCS
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