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Search results for: GENOME-WIDE DNA METHYLATION
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Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis
PublicationMastocytosis is a clinically heterogenous, usually acquired disease of the mast cells with a survival time that depends on the time of onset. It ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The presence of the oncogenic KIT p. D816V gene somatic mutation is a crucial element in the pathogenesis. However, further epigenetic regulation may also affect the expression of genes that...
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Genome-wide DNA methylation profiling of the regenerative MRL/MpJ mouse and two normal strains
PublicationAims We aimed to identify the pivotal differences in the DNA methylation profiles between the regeneration capable MRL/MpJ mouse and reference mouse strains. Materials and Methods Global DNA methylation profiling was performed in ear pinnae, bone marrow, spleen, liver, heart from uninjured adult females of the MRL/MpJ and C57BL/6J and BALB/c. Results and conclusion A number of differentially methylated regions distinguishing between...
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Epigenetic Basis of Regeneration: Analysis of Genomic DNA Methylation Profiles in the MRL/MpJ Mouse
PublicationEpigenetic regulation plays essential role in cell differentiation and dedifferentiation, which are the intrinsic processes involved in regeneration. To investigate the epigenetic basis of regeneration capacity, we choose DNA methylation as one of the most important epigenetic mechanisms and the MRL/MpJ mouse as a model of mammalian regeneration known to exhibit enhanced regeneration response in different organs. We report the...
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Epigenetic regulation and regeneration: the search for differentially methylated genes in the MRL mouse
PublicationThe MRL mouse is an inbred laboratory strain, which was developed in the 60’s of the 20th century and has been extensively used as a model of lupus erythematosus. The regenerative abilities of the strain were discovered in the 90' when the MRL mouse was shown to close 2 mm hole punches made in the ear pinnae four weeks after injury without scarring. The phenomenon has not been observed in other mouse strains, where the holes...
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Beyond Antioxidant Activity: Redox Properties of Catechins May Affect Changes in the DNA Methylation Profile—The Example of SRXN1 Gene
PublicationThe role of catechins in the epigenetic regulation of gene expression has been widely studied; however, if and how this phenomenon relates to the redox properties of these polyphenols remains unknown. Our earlier study demonstrated that exposure of the human colon adenocarcinoma HT29 cell line to these antioxidants affects the expression of redox-related genes. In particular, treatment with (−)-epigallocatechin (EGC) downregulated...
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DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method
PublicationThe impact of catechins on the expression profile of redox-related genes in HT29 cell line has been studied recently by our group using Oxidative Stress RT2 Profiler PCR Array. Within the examined panel of 84 genes, the down-regulation of SRXN1 gene was unique among other up-regulated genes. We hypothesized that the observed down-regulation resulted from DNA methylation and have exploited this observation to choose the proper strategy...
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DNA methylation in cancer development, diagnosis and therapy-multiple opportunities for genotoxic agents to act as methylome disruptors or remediators
PublicationThe role of DNA methylation and recently discovered hydroxymethylation in the function of the human epigenome is currently one of the hottest topics in the life sciences. Progress in this field of research has been further accelerated by the discovery that alterations in the methylome are not only associated with key functions of cells and organisms, such as development, differentiation and gene expression, but may underlie a number...
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Molecular differences in mitochondrial DNA (mtDNA) genomes of dogs with malignant mammary tumours
Open Research DataThe aim of this study was to determine molecular defects in mitochondrial DNA with the use of large-scale genome analysis in malignant canine mammary gland tumours and indicate whether these changes were linked with the carcinogenesis process. With the use of the NGS technology, we sequenced 27 samples of mtDNA isolated from blood and tumours obtained...
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Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups
PublicationMastocytosis is rare disease in which genetic predisposition is not fully understood. The aim of this study was to analyze associations between mastocytosis and single nucleotide polymorphisms (SNPs) by a genome-wide association study (GWAS) approach. A total of 234 patients were enrolled in our study, including 141 with cutaneous mastocytosis (CM; 78 children and 63 adults) and 93 with systemic mastocytosis (SM, all adults)....
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DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
PublicationThe human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization...
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Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential
PublicationBackground The neonatal murine heart is able to regenerate after severe injury; this capacity however, quickly diminishes and it is lost within the first week of life. DNA methylation is an epigenetic mechanism which plays a crucial role in development and gene expression regulation. Under investigation here are the changes in DNA methylation and gene expression patterns which accompany the loss of regenerative potential. Results The...
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The role of epigenetics in regeneration
PublicationComplex changes in chromatin structure and at the transcriptional level occur from the creation of a single parental gamete throughout fertilization, embryo development and the life of an adult organism. Epigenetic changes, such as methylation and hydroxymethylation of DNA or histone methylation and acetylation, are an important part of these processes. Epigenetic regulation has an essential influence on gene expression level. DNA...
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A simple modification to improve the accuracy of methylation-sensitive restriction enzyme quantitative polymerase chain reaction
PublicationDNA digestion with endonucleases sensitive to CpG methylation such as HpaII followed by polymerase chain reaction (PCR) quantitation is commonly used in molecular studies as a simple and inexpensive solution for assessment of region-specific DNA methylation. We observed that the results of such analyses were highly overestimated if mock-digested samples were applied as the reference.We determined DNA methylation levels in several...
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Bortezomib induces methylation changes in neuroblastoma cells that appear to play a significant role in resistance development to this compound
PublicationThe anticancer activity of bortezomib (BTZ) has been increasingly studied in a number of indications and promising results for the use of this treatment have been shown in neuroblastoma. As BTZ treatment is usually administered in cycles, the development of resistance and side effects in patients undergoing therapy with BTZ remains a major challenge for the clinical usage of this compound. Common resistance development also means...
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Catalytic Mechanism of Non-Target DNA Cleavage in CRISPR-Cas9 Revealed by Ab Initio Molecular Dynamics
PublicationCRISPR-Cas9 is a cutting-edge genome editing technology, which uses the endonuclease Cas9 to introduce mutations at desired sites of the genome. This revolutionary tool is promising to treat a myriad of human genetic diseases. Nevertheless, the molecular basis of DNA cleavage, which is a fundamental step for genome editing, has not been established. Here, quantum–classical molecular dynamics (MD) and free energy methods are used...
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Principles of target DNA cleavage and the role of Mg2+ in the catalysis of CRISPR–Cas9
PublicationAt the core of the CRISPR–Cas9 genome-editing technology, the endonuclease Cas9 introduces site-specific breaks in DNA. However, precise mechanistic information to ameliorate Cas9 function is still missing. Here, multimicrosecond molecular dynamics, free energy and multiscale simulations are combined with solution NMR and DNA cleavage experiments to resolve the catalytic mechanism of target DNA cleavage. We show that the conformation...
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Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions
PublicationExperiments on Vicia faba root meristem cells exposed to 150 µM cadmium chloride (CdCl2) were undertaken to analyse epigenetic changes, mainly with respect to DNA replication stress. Histone modifications examined by means of immunofluorescence labeling included: (1) acetylation of histone H3 on lysine 56 (H3K56Ac), involved in transcription, S phase, and response to DNA damage during DNA biosynthesis; (2) dimethylation of histone...
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DDLMS PCR double digestion Ligation Mediated Suppression PCR - a new technique for bacterial specific differentiation
PublicationA new diagnostic kit for K. oxytoca specific differentiation based on ddLMS PCR (ang. double digest ligation Mediated PCR) technique is shown. As a species-specific DNA fragment pehX gene, encoding the enzyme polygalactouronase, was chosen. The genome sequence of K. oxytoca is digested with two endonucleases: AclI and BclI which cut DNA before and after pehX gene. The polymorphic DNA fragments are ligated with AclI-end-specific...
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Molecular Strategy for Survival at a Critical High Temperature in Eschierichia coli
PublicationThe molecular mechanism supporting survival at a critical high temperature (CHT) in Escherichia coli was investigated. Genome-wide screening with a single-gene knockout library provided a list of genes indispensable for growth at 47°C, called thermotolerant genes. Genes for which expression was affected by exposure to CHT were identified by DNA chip analysis. Unexpectedly, the former contents did not overlap with the latter except...
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Novel DNA-binding protein from Nanoarchaeum equitans Kin4-M binds all kinds of nucleic acids
PublicationNanoarchaeum equitans is the only known representative of Archaea phylum Nanoarchaeota and stands out as one of the tiniest known living organism. What is more it has smallest genome, which is only 490.885 base pairs long. It is also one of the most compact genomes. According to predictions about 95% of the DNA encodes proteins or stable RNA. Nanoarchaeum equitans lacks genes for most vital metabolic pathways including lipid, cofactor,...
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Establishing the allosteric mechanism in CRISPR‐Cas9
PublicationAllostery is a fundamental property of proteins, which regulates biochemical information transfer between spatially distant sites. Here, we report on the critical role of molecular dynamics (MD) simulations in discovering the mechanism of allosteric communication within CRISPR‐Cas9, a leading genome editing machinery with enormous promises for medicine and biotechnology. MD revealed how allostery intervenes during at least three...
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Telomere uncapping by common oxidative guanine lesions: Insights from atomistic models
PublicationOxidative damage to DNA is widely known to contribute to aging and disease. This relationship has been extensively studied for telomeres – structures that cap chromosome ends – due to their role in cell proliferation and senescence, and exceptional susceptibility to oxidation. Indeed, the repetitive telomeric DNA sequence contains the 5′-GGG-3′ motif that has the lowest ionization potential of all trinucleotides. Accordingly, experiments...
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Discrimination of hospital isolates of Acinetobacter baumannii using repeated sequences and whole genome alignment differential analysis
PublicationAn optimized method for bacterial strain differentiation, based on combination of Repeated Sequences and Whole Genome Alignment Differential Analysis (RS&WGADA), is presented in this report. In this analysis, 51 Acinetobacter baumannii multidrug-resistance strains from one hospital environment and patients from 14 hospital wards were classified on the basis of polymorphisms of repeated sequences located in CRISPR region, variation...
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Electron-Induced Decomposition of Uracil-5-yl O-(N,N-dimethylsulfamate): Role of Methylation in Molecular Stability
PublicationThe incorporation of modified uracil derivatives into DNA leads to the formation of radical species that induce DNA damage. Molecules of this class have been suggested as radiosensitizers and are still under investigation. In this study, we present the results of dissociative electron attachment to uracil-5-yl O-(N,N-dimethylsulfamate) in the gas phase. We observed the formation of 10 fragment anions in the studied range of electron...
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Molecular identification and genotyping of Staphylococci: genus, species, strains, colnes, lineages, and interspecies exchanges
PublicationStaphylococci are increasingly recognized as etiological agents of many opportunistic human and animal infections, emphasizing the need for a rapid and accurate identification, even to a genotypical level of these bacteria. In the recent years, there has been a significant progress in typing and phylogenetic study of Staphylococcus species. Here, we describe molecular methods used in taxonomy as well as staphylococci characterization....
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The methylome and transcriptome of fetal skin: implications for scarless healing
PublicationAim: Fetal skin is known to heal without scarring. In mice, the phenomenon is observed until the 16–17 day of gestation – the day of transition from scarless to normal healing. The study aims to identify key methylome and transcriptome changes following the transition. Materials & methods: Methylome and transcriptome profiles were analyzed in murine dorsal skin using microarray approach. Results & conclusion: The genes associated...
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Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse
PublicationBackground:Most studies on regenerative medicine focus on cell-based therapies and transplantations.Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensivelyinvestigated in regenerative research. It is known that healing potential decreases with development and devel-opmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerativecapacity.Methods:We...
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Genetic and Epigenetic Aspects of Atopic Dermatitis
PublicationAtopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications...
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Transcriptional activity of epigenetic remodeling genes declines in keratinocytes after in vitro expansion
PublicationPURPOSE: In vitro expansion is an invaluable method to obtain keratinocytes in amounts necessary for effective transplantation therapies. In vitro cell culturing provokes questions concerning potential epigenetic alterations occurring in expanded cells in the context of usefulness for transplantation and safety. The purpose of this study was to investigate as to whether keratinocyte expansion is associated with changes in the activity...
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Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization
PublicationRational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often dicult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing aordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse eects...
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Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures
PublicationFood synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them. However, mechanisms behind this discrepancy were hardly studied. Here, we demonstrate the profound impact of interactions between two common food flavonoids (individual: aglycones quercetin—Q and naringenin—N− or their glycosides rutin—R and naringin—N+ vs. mixed: QN− and RN+) on their electrochemical...
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Extracting functional groups of ALLINI to design derivatives of FDA‐approved drugs: Inhibition of HIV‐1 integrase
PublicationHIV‐1 integrase (IN) is crucial for integration of viral DNA into the host genome and a promising target in development of antiretroviral inhibitors. In this work, six new compounds were designed by linking the structures of two different class of HIV‐1 IN inhibitors (active site binders and allosteric IN inhibitors (ALLINIs)). Among newly designed compounds, INRAT10b was found most potent HIV‐1 IN inhibitor considering different...
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Conservation and diversity of MutS proteins
PublicationThe homologues of MutS, mismatch repair protein, exist in all prokaryotes, with the exception of Actinobacteria, Mollicutes and part of the Archaea. Multiple alignments of 316 MutS amino acid sequences from 169 species revealed conserved residues and sequence motifs distinguishing MutS homologues. All MutS homologues show high conservation within the ATPase domain. MutS1, the homologue responsible for DNA mismatch recognition,...
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Total DNA Methylation Changes Reflect Random Oxidative DNA Damage in Gliomas
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Total DNA methylation as a biomarker of DNA damage and tumor malignancy in intracranial meningiomas
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DNA methylation analysis of benign and atypical meningiomas: correlation between RUNX3 methylation and WHO grade
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Global DNA methylation level in females with idiopathic scoliosis
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Identification of Mitochondrial DNA (NUMTs) in the Nuclear Genome of Daphnia magna
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B13 Can Dna Methylation Be A Factor In The Pathogenesis Of Huntington's Disease?
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Folate/homocysteine metabolism and lung cancer risk among smokers
PublicationBackground: Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis. Objectives: The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers. Study design: The study included 132 lung cancer patients and 396 controls from...
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Genetic and biochemical characterization of yeasts isolated from Antarctic soil samples
PublicationThe Polish Arctowski Station is situated in the maritime Antarctic on the western shore ot' Admiralty Bay and encompasses terrestrial habitats which are not perma-nently covered by ice, in contrast to morę than 90% of the island's surface area. Over the past several decades, stud-ies exploring the soils of those habitats have revealed a considerable diversity of bacteria, filamentous fungi, and, to a lesser extent, yeasts; however,...
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DNA methylation analysis with methylation‐sensitive high‐resolution melting (MS‐HRM) reveals gene panel for glioma characteristics
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Novel Method of Identifying DNA Methylation Fingerprint of Acute Myeloid Leukaemia
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Diagnosis of Brain Tumors Through Global Specific DNA Methylation Analysis
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P04.06 Temozolomide influence on global DNA methylation in glioblastoma cell lines
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Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity
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Mass spectrometry reveals the presence of specific set of epigenetic DNA modifications in the Norway spruce genome
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Bacteriophages as potential tools for use in antimicrobial therapy and vaccine development
PublicationThe constantly growing number of people suffering from bacterial, viral, or fungal infections, parasitic diseases, and cancers prompts the search for innovative methods of disease prevention and treatment, especially based on vaccines and targeted therapy. An additional problem is the global threat to humanity resulting from the increasing resistance of bacteria to commonly used antibiotics. Conventional vaccines based on bacteria...
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Viral infection-oxidative stress/DNA damage-aberrant DNA methylation: separate or interrelated events responsible for genetic instability and childhood ALL development?
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Genome-Wide Identification of Dickeya solani Transcriptional Units Up-Regulated in Response to Plant Tissues From a Crop-Host Solanum tuberosum and a Weed-Host Solanum dulcamara
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