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Wyniki wyszukiwania dla: N-METHYLATION
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Convenient and efficient N-methylation of secondary amines under solvent-free ball milling conditions
PublikacjaIn the present work, we report the development of a rapid, efcient, and solvent-free procedure for the N-methylation of secondary amines under mechanochemical conditions. After optimization of the milling parameters, a vibrational ball mill was used to synthesize 26 tertiary N-methylated amine derivatives in a short time of 20 min (30 Hz frequency) and high yields ranging from 78 to 95%. An exception was compounds having a hydroxyl...
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Electron-Induced Decomposition of Uracil-5-yl O-(N,N-dimethylsulfamate): Role of Methylation in Molecular Stability
PublikacjaThe 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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Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures
PublikacjaFood 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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The Reactivity of Phosphanylphosphinidene Complexes of Transition Metals Toward Terminal Dihaloalkanes
PublikacjaThe reactivities of phosphanylphosphinidene complexes [(DippN)2W(Cl)(η2-P−PtBu2)]− (1), [(pTol3P)2Pt(η2- P=PtBu2)] (2), and [(dppe)Pt(η2-P=PtBu2)] (3) toward dihaloalkanes and methyl iodide were investigated. The reactions of the anionic tungsten complex (1) with stochiometric Br(CH2)nBr (n = 3, 4, 6) led to the formation of neutral complexes with a tBu2PP(CH2)3Br ligand or neutral dinuclear complexes with unusual tetradentate...
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Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential
PublikacjaBackground 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
PublikacjaComplex 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
PublikacjaDNA 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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Epigenetic Basis of Regeneration: Analysis of Genomic DNA Methylation Profiles in the MRL/MpJ Mouse
PublikacjaEpigenetic 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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Beyond Antioxidant Activity: Redox Properties of Catechins May Affect Changes in the DNA Methylation Profile—The Example of SRXN1 Gene
PublikacjaThe 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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Paweł Możejko dr hab.
Osoby -
Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis
PublikacjaMastocytosis 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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DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method
PublikacjaThe 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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Propeller-Like Chirality of Methyl-Tris (2,6-diisopropylphenoxy)Silylsulfide
PublikacjaTwo new methylsilylsulfides are synthesized. Propeller-like chirality is described for triaryloxysilanethiol and its methyl derivative. S-methylation of the silanethiol lowers the overall symmetry of the unit cell.
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DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
PublikacjaThe 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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Methylation effect in e−— scattering on methyl-substituted ethylenes
PublikacjaMethylation effect has been observed and studied in electron-scattering from selected hydrocarbon molecules. In measured total cross section (TCS) functions we have noticed energy shifts and changes in the intensity of observed structures.
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Genome-wide DNA methylation profiling of the regenerative MRL/MpJ mouse and two normal strains
PublikacjaAims 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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Novel Resveratrol-Based Substrates for Human Hepatic, Renal, and Intestinal UDP-Glucuronosyltransferases
PublikacjaTrans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anti-carcinogenic, and anti-aging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-Glucuronosyltransferases (UGTs). The aim of the current study was to test the hypothesis that the limited bioavailability of tRes can be improved by modifying its structure to create analogs...
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Bortezomib induces methylation changes in neuroblastoma cells that appear to play a significant role in resistance development to this compound
PublikacjaThe 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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Epigenetic regulation and regeneration: the search for differentially methylated genes in the MRL mouse
PublikacjaThe 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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Role of methylation in electron scattering on X(CH3)4 (X = C, Si, Ge) molecules
PublikacjaTotal cross sections (TCS) for low-energy electron scattering from X(CH3)4 (where X = C, Si, Ge) molecules have been measured using linear transmission method. Present results and those obtained previously for XH4 molecules were used to determine how methylation of the target is reflected in TCS energy dependence.
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Electron Scattering on X(CH3)4 Molecules: Applicability of Simple Additivity Rule and Role of Methylation
PublikacjaTo investigate influence of target methylation (substitution of a hydrogen atom by methyl group) on electron-collision processes we compare absolute total cross sections for XH4 and X(CH3)4 molecules, where X is Si and Ge, respectively. We also compare experimental TCSs energy dependencies with estimated data obtained using simple formula and TCSs for methyl group and those for SiH4 and GeH4. Electron-scattering TCSs for mentioned...
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Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions
PublikacjaExperiments 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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DNA methylation in cancer development, diagnosis and therapy-multiple opportunities for genotoxic agents to act as methylome disruptors or remediators
PublikacjaThe 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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DNA methylation pattern is altered in childhood T-cell acute lymphoblastic leukemia patients as compared with normal thymic subsets: insights into CpG island methylator phenotype in T-ALL
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TOTAL CROSS SECTION MEASUREMENTS FOR ELECTRON SCATTERING ON METHYL FORMATE (HCOOCH3) MOLECULE: METHYLATION EFFECT
PublikacjaWe present the absolute total cross section (TCS) for electron scattering from the methyl formate (HCOOCH3) molecule measured in the 10-300 eV energy range, with electrostatic electron spectrometer working in the linear transmission mode. Comparison of TCS for the HCOOCH3 molecule with that measured earlier for the formic acid (HCOOH) compound manifests the methylation effect i.e. the response of the electron scattering dynamics...
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The methylome and transcriptome of fetal skin: implications for scarless healing
PublikacjaAim: 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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Elimination of excretion of ibuprofen and its metabolites in horses
PublikacjaAnalytical procedure based on application of gas chromatography-mass spectrometry (GC-MS) at the step of detection, identification and quantitation of ibuprofen (IBU) and detection of its metabolites – 1-hydroxyibuprofen (1-OH IBU) and carboxyibuprofen (CBX IBU) in horse urine by selected ion monitoring mode after sample preparation covering extraction at pH 3-4 and methylation has been used. The ions at m/z 161, 220 (methylated...
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Genetic and Epigenetic Aspects of Atopic Dermatitis
PublikacjaAtopic 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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Electron scattering from 2-methyl–1,3-butadiene,C5H8, molecules: Role of methylation
PublikacjaWe report cross-section results from experimental and theoretical investigations into electron collisions with the 2-methyl–1,3-butadiene [C5H8] molecule. The current results are compared with our previous results for the 1,3-butadiene [C4H6] molecule, a structural homologue of 2-methyl–1,3-butadiene, to investigate how the methylation (the substitution of hydrogen atom by a methyl group) affects the shape and/or magnitude of the...
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Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse
PublikacjaBackground: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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Transcriptional activity of epigenetic remodeling genes declines in keratinocytes after in vitro expansion
PublikacjaPURPOSE: 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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Electron collisions with methyl-substituted ethylenes: Cross section measurements and calculations for 2-methyl–2-butene and 2,3-dimethyl–2-butene
PublikacjaWe report electron-scattering cross sections determined for 2-methyl–2-butene [(H3C)HC==C(CH3)2] and 2,3-dimethyl–2-butene [(H3C)2C=C(CH3)2] molecules. Absolute grand-total cross sections (TCSs) were measured for incident electron energies in the 0.5–300 eV range, using a linear electron-transmission technique. The experimental TCS energy dependences for the both targets appear to be very similar with respect to the shape. In each...
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An investigation on the chemistry of the R2P=P ligand: reactions of a phosphanylphosphinidene complex of tungsten(VI) with electrophilic reagents
PublikacjaThe nucleophilic properties of the title compound [(2,6-i-Pr2C6H3N)2(Cl)W(η2-t-Bu2PvP)]Li·3DME (1) were investigated in reactions with selected electrophilic reagents such as MeI, M(CO)5THF (M = Cr, Mo, W), AlCl3, and GaCl3. Methylation of 1 by MeI yields phosphanylphosphido complexes [(2,6-i-Pr2C6H3N)2W(X)(1,2-η-t-Bu2PvP–CH3)] (X = Cl, I) (2-Cl/2-I) with the formation of a new P–C bond. Moreover, 1 reacts with electrophilic compounds...
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Folate/homocysteine metabolism and lung cancer risk among smokers
PublikacjaBackground: 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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Investigation of interaction between xanthene dye rhodamine B and metagenomic-derivated methylthioadenosine phosphorylase RSFP
PublikacjaIn the previous study we found that the expression of the metagenomic - derived methylthioadenosine phosphorylase gene (rsfp) in E. coli cells and the presence of rhodamine B in the growth medium were crucial for the pink fluorescence of one E. coli colony from Antarctic soil metagenomic library (Cieśliński et al., 2009). In this study, rsfp gene expression was induced by an arabinose promoter in an LMG194 E. coli strain and the...
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Effects of beach wrack on the fate of mercury at the land-sea interface – A preliminary study
PublikacjaSince the 1970s, the amount of aquatic plants and algae debris, called beach wrack (BW), has increased along the shores of industrialised regions. The strong ability of primary producers to accumulate pollutants can potentially result in their deposition on the beach along with the BW. Despite that, the fate and impact of such pollutants on sandy beach ecosystems have not been investigated so far. This study examines the fate...
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Determination of the Major By-Products of Citrus hystrix Peel and Their Characteristics in the Context of Utilization in the Industry
PublikacjaKaffir lime (Citrus hystrix) is a popular citrus in Southeast Asia. Despite the growing interest in the peel of the fruit, the leaves are the most frequently used part of the fruit. The aim of the study was to determine the main by-products of the peel, such as pectins, minerals, essential oil, and bioactive compounds, and to evaluate the possibility of using them in various branches of industry. In the study of the essential oil...