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Microbiology Spectrum Aug 2016Adenoviruses are a highly prevalent infection that can cause a range of clinical syndromes in immunocompromised patients, ranging from localized disease of the... (Review)
Review
Adenoviruses are a highly prevalent infection that can cause a range of clinical syndromes in immunocompromised patients, ranging from localized disease of the respiratory tract, gastrointestinal tract, or urinary tract to disseminated disease. Adenovirus infections may develop in this unique population as the result of primary infection or reactivation of latent virus. Disease can be potentially progressive with high rates of mortality in patients with pneumonia and disseminated disease. Fortunately, cidofovir and its lipid ester, brincidofovir, appear to be effective for the treatment of adenovirus, although neither is specifically approved for this indication. Adenovirus should always be considered when immunocompromised patients present with any clinical syndrome that could be compatible with adenoviral infection. Once disease is suspected, cultures or molecular testing of appropriate specimens should be obtained and blood should be sent for adenovirus polymerase chain reaction (PCR) whenever adenovirus is suspected. Monitoring of quantitative viral loads in blood is helpful in predicting response to therapy with a significant drop (>1 log) associated with a higher probability of clinical response.
Topics: Adenoviridae Infections; Antiviral Agents; Cidofovir; Cytosine; Diagnostic Tests, Routine; Disease Susceptibility; Drug Monitoring; Humans; Immunocompromised Host; Organophosphonates
PubMed: 27726766
DOI: 10.1128/microbiolspec.DMIH2-0020-2015 -
Bioinformatics (Oxford, England) Jun 2011A combination of bisulfite treatment of DNA and high-throughput sequencing (BS-Seq) can capture a snapshot of a cell's epigenomic state by revealing its genome-wide...
SUMMARY
A combination of bisulfite treatment of DNA and high-throughput sequencing (BS-Seq) can capture a snapshot of a cell's epigenomic state by revealing its genome-wide cytosine methylation at single base resolution. Bismark is a flexible tool for the time-efficient analysis of BS-Seq data which performs both read mapping and methylation calling in a single convenient step. Its output discriminates between cytosines in CpG, CHG and CHH context and enables bench scientists to visualize and interpret their methylation data soon after the sequencing run is completed.
AVAILABILITY AND IMPLEMENTATION
Bismark is released under the GNU GPLv3+ licence. The source code is freely available from www.bioinformatics.bbsrc.ac.uk/projects/bismark/.
Topics: Cytosine; DNA; DNA Methylation; Sequence Analysis, DNA; Software; Sulfites
PubMed: 21493656
DOI: 10.1093/bioinformatics/btr167 -
Proceedings of the National Academy of... Feb 1977DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments...
DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments then identify the positions of that base. We describe reactions that cleave DNA preferentially at guanines, at adenines, at cytosines and thymines equally, and at cytosines alone. When the products of these four reactions are resolved by size, by electrophoresis on a polyacrylamide gel, the DNA sequence can be read from the pattern of radioactive bands. The technique will permit sequencing of at least 100 bases from the point of labeling.
Topics: Adenine; Base Sequence; Biochemical Phenomena; Biochemistry; Cytosine; DNA; DNA Restriction Enzymes; Guanine; Hydrazines; Methods; Nucleic Acid Hybridization; Thymine
PubMed: 265521
DOI: 10.1073/pnas.74.2.560 -
Nature Chemical Biology Aug 20235-methylcytosine (5mC) is the most important DNA modification in mammalian genomes. The ideal method for 5mC localization would be both nondestructive of DNA and direct,...
5-methylcytosine (5mC) is the most important DNA modification in mammalian genomes. The ideal method for 5mC localization would be both nondestructive of DNA and direct, without requiring inference based on detection of unmodified cytosines. Here we present direct methylation sequencing (DM-Seq), a bisulfite-free method for profiling 5mC at single-base resolution using nanogram quantities of DNA. DM-Seq employs two key DNA-modifying enzymes: a neomorphic DNA methyltransferase and a DNA deaminase capable of precise discrimination between cytosine modification states. Coupling these activities with deaminase-resistant adapters enables accurate detection of only 5mC via a C-to-T transition in sequencing. By comparison, we uncover a PCR-related underdetection bias with the hybrid enzymatic-chemical TET-assisted pyridine borane sequencing approach. Importantly, we show that DM-Seq, unlike bisulfite sequencing, unmasks prognostically important CpGs in a clinical tumor sample by not confounding 5mC with 5-hydroxymethylcytosine. DM-Seq thus offers an all-enzymatic, nondestructive, faithful and direct method for the reading of 5mC alone.
Topics: Animals; 5-Methylcytosine; DNA Methylation; Cytosine; DNA; Sequence Analysis, DNA; Mammals
PubMed: 37322153
DOI: 10.1038/s41589-023-01318-1 -
Proceedings of the National Academy of... Mar 1992The modulation of DNA-protein interactions by methylation of protein-binding sites in DNA and the occurrence in genomic imprinting, X chromosome inactivation, and...
The modulation of DNA-protein interactions by methylation of protein-binding sites in DNA and the occurrence in genomic imprinting, X chromosome inactivation, and fragile X syndrome of different methylation patterns in DNA of different chromosomal origin have underlined the need to establish methylation patterns in individual strands of particular genomic sequences. We report a genomic sequencing method that provides positive identification of 5-methylcytosine residues and yields strand-specific sequences of individual molecules in genomic DNA. The method utilizes bisulfite-induced modification of genomic DNA, under conditions whereby cytosine is converted to uracil, but 5-methylcytosine remains nonreactive. The sequence under investigation is then amplified by PCR with two sets of strand-specific primers to yield a pair of fragments, one from each strand, in which all uracil and thymine residues have been amplified as thymine and only 5-methylcytosine residues have been amplified as cytosine. The PCR products can be sequenced directly to provide a strand-specific average sequence for the population of molecules or can be cloned and sequenced to provide methylation maps of single DNA molecules. We tested the method by defining the methylation status within single DNA strands of two closely spaced CpG dinucleotides in the promoter of the human kininogen gene. During the analysis, we encountered in sperm DNA an unusual methylation pattern, which suggests that the high methylation level of single-copy sequences in sperm may be locally modulated by binding of protein factors in germ-line cells.
Topics: 5-Methylcytosine; Base Sequence; Cytosine; DNA; Humans; Kininogens; Methylation; Molecular Sequence Data; Oligodeoxyribonucleotides; Polymerase Chain Reaction; Promoter Regions, Genetic; Sulfites
PubMed: 1542678
DOI: 10.1073/pnas.89.5.1827 -
Cellular and Molecular Life Sciences :... Feb 2014DNA methylation has been studied comprehensively and linked to both normal neurodevelopment and neurological diseases. The recent identification of several new DNA... (Review)
Review
DNA methylation has been studied comprehensively and linked to both normal neurodevelopment and neurological diseases. The recent identification of several new DNA modifications, including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, has given us a new perspective on the previously observed plasticity in 5mC-dependent regulatory processes. Here, we review the latest research into these cytosine modifications, focusing mainly on their roles in neurodevelopment and diseases.
Topics: 5-Methylcytosine; Cytosine; DNA Methylation; DNA-Cytosine Methylases; Humans; Models, Molecular; Nervous System Diseases; Neurogenesis
PubMed: 23912899
DOI: 10.1007/s00018-013-1433-y -
Epigenomics 2014
Topics: 5-Methylcytosine; Animals; Cytosine; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Humans; Promoter Regions, Genetic
PubMed: 25531248
DOI: 10.2217/epi.14.48 -
Biomolecular Concepts Jun 2016Chemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of... (Review)
Review
Chemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of 5-methylcytosine (5-mC) has been extensively studied, little is known about the function(s) of relatively rarer and underappreciated cytosine modifications including 5-hydroxymethylcytosine (5-hmC). The discovery that ten-eleven translocation (Tet) proteins mediate conversion of 5-mC to 5-hmC, and other oxidation derivatives, sparked renewed interest to understand the biological role of 5-hmC. Studies examining total 5-hmC levels revealed the highly dynamic yet tissue-specific nature of this modification, implicating a role in epigenetic regulation and development. Intriguingly, 5-hmC levels are highest during early development and in the brain where abnormal patterns of 5-hmC have been observed in disease conditions. Thus, 5-hmC adds to the growing list of epigenetic modifications with potential utility in clinical applications and warrants further investigation. This review discusses the emerging functional roles of 5-hmC in normal and disease states, focusing primarily on insights provided by recent studies exploring the genome-wide distribution of this modification in mammals.
Topics: 5-Methylcytosine; Animals; Cytosine; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans; Organ Specificity
PubMed: 27356236
DOI: 10.1515/bmc-2016-0011 -
Bulletin Du Cancer Mar 2004Nucleoside analogues are commonly used in the treatment of hematological malignancies and solid tumors. As antimetabolites, these drugs act by disrupting DNA synthesis... (Review)
Review
Nucleoside analogues are commonly used in the treatment of hematological malignancies and solid tumors. As antimetabolites, these drugs act by disrupting DNA synthesis and inducing apoptosis following their incorporation into DNA. Troxacitabine (Troxatyl) is the first nucleoside analogue with anticancer activity that has an unnatural stereochemical configuration. Its broad preclinical antineoplastic spectrum led to its clinical development. Summaries of the preclinical data and of the initial phase I and II clinical trials are presented.
Topics: Acute Disease; Animals; Antineoplastic Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cytosine; Dioxolanes; Drug Screening Assays, Antitumor; Humans; Leukemia; Neoplasms
PubMed: 15171046
DOI: No ID Found -
Genomics Nov 2014
Topics: 5-Methylcytosine; Animals; Cytosine; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 25449535
DOI: 10.1016/j.ygeno.2014.10.007