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https://www.readbyqxmd.com/read/27915307/diversity-and-antifungal-drug-susceptibility-of-cryptococcus-isolates-in-thailand
#1
Navaporn Worasilchai, Marut Tangwattanachuleeporn, Kornvalee Meesilpavikkai, Claudia Folba, Mourine Kangogo, Uwe Groß, Michael Weig, Oliver Bader, Ariya Chindamporn
Yeasts of the Cryptococcus species complex are the causative agent of cryptococcosis, especially in human immunodeficiency virus (HIV) positive individuals. Cerebral or disseminated cryptococcosis has a very high mortality rate worldwide, including in Thailand. Additionally, an increasing rate of antifungal drug resistant cryptococcal isolates has been reported in several neighboring countries, complicating therapeutic approaches. To understand the situation of this infection in Thailand, we retrospectively investigated the molecular epidemiology and antifungal drug resistance in a collection of 74 clinical, 52 environmental and two veterinary isolates using the URA5-RFLP for typing and the EUCAST guideline for susceptibility testing...
December 3, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#2
Dongxue Wang, Hideharu Hashimoto, Xing Zhang, Benjamin G Barwick, Sagar Lonial, Lawrence H Boise, Paula M Vertino, Xiaodong Cheng
The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5'-CACGTG-3'. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27826843/structure-and-function-of-tet-enzymes
#3
Xiaotong Yin, Yanhui Xu
Mammalian DNA methylation mainly occurs at the carbon-C5 position of cytosine (5mC). TET enzymes were discovered to successively oxidize 5mC to 5-hydromethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). TET enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis. In this chapter, we will discuss the discovery of TET-mediated 5mC oxidation and the structure, function, and regulation of TET enzymes...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27805801/tet1-mediated-oxidation-of-5-formylcytosine-5fc-to-5-carboxycytosine-5cac-in-rna
#4
Maria Basanta-Sanchez, Rui Wang, Zhenzhen Liu, Xiaohan Ye, Minyong Li, Xiaodong Shi, Paul Agris, Yubin Zhou, Yun Huang, Jia Sheng
It has been revealed recently that 5-methylcytosine (5mC) in mRNA, similar as in DNA, can also be oxidized to produce 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), implying the potential regulatory roles of this post-transcriptional RNA modification. In this study, we demonstrate the in vitro oxidation of 5fC to 5-carboxycytidine (5caC) by the catalytic domain of mammalian ten-eleven translocation enzyme (TET1) in different RNA contexts. We observed that this oxidation process has very low sequence dependence and can take place in single stranded, double stranded or hairpin forms of RNA sequences, although the overall conversion yields are low...
November 2, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27742099/species-diversity-of-aspergillus-section-versicolores-in-clinical-samples-and-antifungal-susceptibility
#5
João Paulo Zen Siqueira, Deanna A Sutton, Dania García, Josepa Gené, Pamela Thomson, Nathan Wiederhold, Josep Guarro
Aspergillus section Versicolores includes species of clinical relevance and many others that have been poorly studied but are occasionally found in clinical samples. The aim of this study was to investigate, using a multilocus phylogenetic approach, the spectrum of species of the section Versicolores and to determine their in vitro antifungal susceptibility. The study was based on a set of 77 clinical isolates from different USA medical centres, which had been previously identified as belonging to this section...
November 2016: Fungal Biology
https://www.readbyqxmd.com/read/27587669/luxglm-a-probabilistic-covariate-model-for-quantification-of-dna-methylation-modifications-with-complex-experimental-designs
#6
Tarmo Äijö, Xiaojing Yue, Anjana Rao, Harri Lähdesmäki
MOTIVATION: 5-methylcytosine (5mC) is a widely studied epigenetic modification of DNA. The ten-eleven translocation (TET) dioxygenases oxidize 5mC into oxidized methylcytosines (oxi-mCs): 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methylation modifications have multiple functions. For example, 5mC is shown to be associated with diseases and oxi-mC species are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, among others, but the detailed mechanisms are poorly understood...
September 1, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27587280/analysis-of-the-machinery-and-intermediates-of-the-5hmc-mediated-dna-demethylation-pathway-in-aging-on-samples-from-the-mark-age-study
#7
Elisabetta Valentini, Michele Zampieri, Marco Malavolta, Maria Giulia Bacalini, Roberta Calabrese, Tiziana Guastafierro, Anna Reale, Claudio Franceschi, Antti Hervonen, Bernhard Koller, Jürgen Bernhardt, P Eline Slagboom, Olivier Toussaint, Ewa Sikora, Efstathios S Gonos, Nicolle Breusing, Tilman Grune, Eugène Jansen, Martijn E T Dollé, María Moreno-Villanueva, Thilo Sindlinger, Alexander Bürkle, Fabio Ciccarone, Paola Caiafa
Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players...
August 29, 2016: Aging
https://www.readbyqxmd.com/read/27585398/detection-of-modified-forms-of-cytosine-using-sensitive-immunohistochemistry
#8
Abdulkadir Abakir, Lee Wheldon, Andrew D Johnson, Patrick Laurent, Alexey Ruzov
Methylation of cytosine bases (5-methylcytosine, 5mC) occurring in vertebrate genomes is usually associated with transcriptional silencing. 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are the recently discovered modified cytosine bases produced by enzymatic oxidation of 5mC, whose biological functions remain relatively obscure. A number of approaches ranging from biochemical to antibody based techniques have been employed to study the genomic distribution and global content of these modifications in various biological systems...
August 16, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27557497/the-emerging-insights-into-catalytic-or-non-catalytic-roles-of-tet-proteins-in-tumors-and-neural-development
#9
Hao Lian, Wen-Bin Li, Wei-Lin Jin
The Ten-eleven translocation (TET) proteins have been recently identified as critical regulators in epigenetic modification, especially in the methylation of cytosine in DNA. TET-mediated DNA oxidation plays prominent roles in a wide variety of physiological and pathological processes, especially in tumor and neural development. TET proteins execute stepwise enzymatic conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to the more proverbial enzymatic role of TET proteins, TET proteins also possess non-enzymatic activity, through interacting with some epigenetic modifiers...
August 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27466503/isocitrate-dehydrogenase-2-dysfunction-contributes-to-5-hydroxymethylcytosine-depletion-in-gastric-cancer-cells
#10
Nan-Hua Chou, Chung-Yu Tsai, Ya-Ting Tu, Kuo-Chiang Wang, Chi-Hsiang Kang, Po-Min Chang, Guan-Cheng Li, Hing-Chung Lam, Shiuh-Inn Liu, Kuo-Wang Tsai
The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues...
August 2016: Anticancer Research
https://www.readbyqxmd.com/read/27461566/combined-treatment-based-on-lysomustine-administration-with-mesenchymal-stem-cells-expressing-cytosine-deaminase-therapy-leads-to-pronounced-murine-lewis-lung-carcinoma-growth-inhibition
#11
Lyudmila S Krassikova, Saida S Karshieva, Ivan B Cheglakov, Alexander V Belyavsky
BACKGROUND: The combination of stem cell-based gene therapy with chemotherapy comprises an advantageous strategy that results in a reduction of system toxicity effects and an improvement in the general efficacy of treatment. In the present study, we estimated the efficacy of adipose tissue-derived mesenchymal stem cells (AT-MSCs) expressing cytosine deaminase (CDA) combined with lysomustine chemotherapy in mice bearing late stage Lewis lung carcinoma (LLC). METHODS: Adipose tissue-derived mesenchymal stem cells were transfected with non-insert plasmid construct transiently expressing fused cytosine deaminase-uracil phosphoribosyltransferase protein (CDA/UPRT) or the same construct fused with Herpes Simplex Virus Type1 tegument protein VP22 (CDA/UPRT/VP22)...
September 2016: Journal of Gene Medicine
https://www.readbyqxmd.com/read/27460669/simple-and-accurate-single-base-resolution-analysis-of-5-hydroxymethylcytosine-by-catalytic-oxidative-bisulfite-sequencing-using-micelle-incarcerated-oxidants
#12
Seketsu Fukuzawa, Saori Takahashi, Kazuo Tachibana, Shoji Tajima, Isao Suetake
Oxidation of 5-methylcytosine (5mC) is catalyzed by ten-eleven translocation (TET) enzymes to produce 5-hydroxymethylcytosine (5hmC) and following oxidative products. The oxidized nucleotides were shown to be the intermediates for DNA demethylation, as the nucleotides are removed by base excision repair system initiated by thymine DNA glycosylase. A simple and accurate method to determine initial oxidation product 5hmC at single base resolution in genomic DNA is necessary to understand demethylation mechanism...
September 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27414653/resistance-surveillance-in-candida-albicans-a-five-year-antifungal-susceptibility-evaluation-in-a-brazilian-university-hospital
#13
Isabela Haddad Peron, Franqueline Reichert-Lima, Ariane Fidelis Busso-Lopes, Cristiane Kibune Nagasako, Luzia Lyra, Maria Luiza Moretti, Angelica Zaninelli Schreiber
Candida albicans caused 44% of the overall candidemia episodes from 2006 to 2010 in our university tertiary care hospital. As different antifungal agents are used in therapy and also immunocompromised patients receive fluconazole prophylaxis in our institution, this study aimed to perform an antifungal susceptibility surveillance with the C.albicans bloodstream isolates and to characterize the fluconazole resistance in 2 non-blood C.albicans isolates by sequencing ERG11 gene. The study included 147 C. albicans bloodstream samples and 2 fluconazole resistant isolates: one from oral cavity (LIF 12560 fluconazole MIC: 8μg/mL) and one from esophageal cavity (LIF-E10 fluconazole MIC: 64μg/mL) of two different patients previously treated with oral fluconazole...
2016: PloS One
https://www.readbyqxmd.com/read/27375887/hydrogen-bonding-patterns-in-5-fluoro-cytosine-melamine-co-crystal-4-1
#14
Marimuthu Mohana, Packianathan Thomas Muthiah, Liurukara D Sanjeewa, Colin D McMillen
The asymmetric unit of the title compound, 4C4H4FN3O·C3H6N6, comprises of two independent 5-fluoro-cytosine (5FC) mol-ecules (A and B) and one half-mol-ecule of melamine (M). The other half of the melamine mol-ecule is generated by a twofold axis. 5FC mol-ecules A and B are linked through two different homosynthons [R 2 (2)(8) ring motif]; one is formed via a pair of N-H⋯O hydrogen bonds and the second via a pair of N-H⋯N hydrogen bonds. In addition to this pairing, the O atoms of 5FC mol-ecules A and B inter-act with the N2 amino group on both sides of the melamine mol-ecule, forming a DDAA array of quadruple hydrogen bonds and generating a supra-molecular pattern...
April 1, 2016: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/27356509/in-vivo-genome-wide-profiling-reveals-a-tissue-specific-role-for-5-formylcytosine
#15
Mario Iurlaro, Gordon R McInroy, Heather E Burgess, Wendy Dean, Eun-Ang Raiber, Martin Bachman, Dario Beraldi, Shankar Balasubramanian, Wolf Reik
BACKGROUND: Genome-wide methylation of cytosine can be modulated in the presence of TET and thymine DNA glycosylase (TDG) enzymes. TET is able to oxidise 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TDG can excise the oxidative products 5fC and 5caC, initiating base excision repair. These modified bases are stable and detectable in the genome, suggesting that they could have epigenetic functions in their own right. However, functional investigation of the genome-wide distribution of 5fC has been restricted to cell culture-based systems, while its in vivo profile remains unknown...
June 29, 2016: Genome Biology
https://www.readbyqxmd.com/read/27281647/methylation-assisted-bisulfite-sequencing-to-simultaneously-map-5fc-and-5cac-on-a-genome-wide-scale-for-dna-demethylation-analysis
#16
Francesco Neri, Danny Incarnato, Anna Krepelova, Caterina Parlato, Salvatore Oliviero
Active DNA demethylation is mediated by ten-eleven translocation (TET) proteins that progressively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). We have developed a methylation-assisted bisulfite sequencing (MAB-seq) method that enables direct genome-scale mapping and quantification of 5fC and 5caC marks together at single-base resolution. In bisulfite sequencing (BS), unmethylated cytosine residues (Cs), 5fCs and 5caCs, are converted to uracil and cannot be discriminated from each other...
July 2016: Nature Protocols
https://www.readbyqxmd.com/read/27172168/base-resolution-profiling-of-active-dna-demethylation-using-mab-seq-and-camab-seq
#17
Hao Wu, Xiaoji Wu, Yi Zhang
A complete understanding of the function of the ten-eleven translocation (TET) family of dioxygenase-mediated DNA demethylation requires new methods to quantitatively map oxidized 5-methylcytosine (5mC) bases at high resolution. We have recently developed a methylase-assisted bisulfite sequencing (MAB-seq) method that allows base-resolution mapping of 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), two oxidized 5mC bases indicative of active DNA demethylation events. In standard bisulfite sequencing (BS-seq), unmodified C, 5fC and 5caC are read as thymine; thus 5fC and 5caC cannot be distinguished from C...
June 2016: Nature Protocols
https://www.readbyqxmd.com/read/27135278/evaluation-of-antifungal-combination-against-cryptococcus-spp
#18
Franqueline Reichert-Lima, Ariane F Busso-Lopes, Luzia Lyra, Isabela Haddad Peron, Hideaki Taguchi, Yuzuru Mikami, Katsuiko Kamei, Maria Luiza Moretti, Angelica Z Schreiber
The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin (AMB), 5-flucytosine (5FC), fluconazole (FCZ), voriconazole (VRZ), itraconazole (ITZ) and terbinafine (TRB)...
September 2016: Mycoses
https://www.readbyqxmd.com/read/26975309/a-probabilistic-generative-model-for-quantification-of-dna-modifications-enables-analysis-of-demethylation-pathways
#19
Tarmo Äijö, Yun Huang, Henrik Mannerström, Lukas Chavez, Ageliki Tsagaratou, Anjana Rao, Harri Lähdesmäki
We present a generative model, Lux, to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications...
2016: Genome Biology
https://www.readbyqxmd.com/read/26841909/mechanistic-insights-into-the-recognition-of-5-methylcytosine-oxidation-derivatives-by-the-suvh5-sra-domain
#20
Eerappa Rajakumara, Naveen Kumar Nakarakanti, M Angel Nivya, Mutyala Satish
5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context of a CG sequence by the SET- and RING-associated domain (SRA) of the SUVH5 protein (SUVH5 SRA). Using calorimetric measurements, we demonstrate that the SRA domain binds to the hydroxymethylated CG (5hmCG) DNA duplex in a similar manner to methylated CG (5mCG)...
2016: Scientific Reports
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