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https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#1
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28430929/promoter-polymorphism-rs886205-genotype-interacts-with-dna-methylation-of-the-aldh2-regulatory-region-in-alcohol-dependence
#2
Hansi Pathak, Helge Frieling, Stefan Bleich, Alexander Glahn, Annemarie Heberlein, Mani Haschemi Nassab, Thomas Hillemacher, Alexandra Burkert, Mathias Rhein
Aims: Aldehyde dehydrogenase 2 (ALDH2) protects cells from ethanol toxicity by metabolizing acetaldehyde. We studied the single nucleotide polymorphism (SNP) rs886205s located between a negative and a positive regulating promoter element in the ALDH2 gene. The negative regulatory region was already associated with differential DNA methylation in the two allele variations of rs886205 SNP. Another CpG island, in the positive regulatory region of the ALDH2 promoter, extends through the SNP rs886205 and a nuclear receptor response element...
May 1, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28428825/comprehensive-evaluation-of-genome-wide-5-hydroxymethylcytosine-profiling-approaches-in-human-dna
#3
Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M Gould, Shalima S Nair, Susan J Clark, Clare Stirzaker
BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28428040/design-synthesis-and-docking-studies-of-quinazoline-analogues-bearing-aryl-semicarbazone-scaffolds-as-potent-egfr-inhibitors
#4
Yuanbiao Tu, Caolin Wang, Shan Xu, Zhou Lan, Wei Li, Jiaqian Han, Yuanzhang Zhou, Pengwu Zheng, Wufu Zhu
Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a-o and 10a-o) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o was further evaluated for the inhibitory activity against EGFR kinases. Four of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM to nanomole range. Two of them are equal to more active than positive control afatinib against one or more cell lines...
April 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28427185/transcriptional-landscape-of-human-cancers
#5
Mengyuan Li, Qingrong Sun, Xiaosheng Wang
The homogeneity and heterogeneity in somatic mutations, copy number alterations and methylation across different cancer types have been extensively explored. However, the related exploration based on transcriptome data is lacking. In this study we explored gene expression profiles across 33 human cancer types using The Cancer Genome Atlas (TCGA) data. We identified consistently upregulated genes (such as E2F1, EZH2, FOXM1, MYBL2, PLK1, TTK, AURKA/B and BUB1) and consistently downregulated genes (such as SCARA5, MYOM1, NKAPL, PEG3, USP2, SLC5A7 and HMGCLL1) across various cancers...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424740/essential-role-of-long-non-coding-rnas-in-de-novo-chromatin-modifications-the-genomic-address-code-hypothesis
#6
Ken Nishikawa, Akira R Kinjo
The epigenome, i.e., the whole of chromatin modifications, is transferred from mother to daughter cells during cell differentiation. When de novo chromatin modifications (establishment or erasure of, respectively, new or pre-existing DNA methylations and/or histone modifications) are made in a daughter cell, however, it has a different epigenome than its mother cell. Although de novo chromatin modification is an important event that comprises elementary processes of cell differentiation, its molecular mechanism remains poorly understood...
April 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28416484/ssrp1-cooperates-with-parp-and-xrcc1-to-facilitate-single-strand-dna-break-repair-by-chromatin-priming
#7
Ying Gao, Changling Li, Leizhen Wei, Yaqun Teng, Satoshi Nakajima, Xiukai Chen, Jianquan Xu, Brittany Leger, Hongqiang Ma, Stephen Spagnol, Yong Wan, Kris Dahl, Yang Liu, Arthur Levine, Li Lan
DNA single strand breaks (SSB) are the most common form of DNA damage, requiring repair processes that to initiate must overcome chromatin barriers. The FACT complex comprised of the SSRP1 and SPT16 proteins are important for maintaining chromatin integrity, with SSRP1 acting as an histone H2A/H2B chaperone in chromatin disassembly during DNA transcription, replication and repair. In this study, we show that SSRP1 but not SPT16 is critical for cell survival after ionizing radiation or methyl methanesulfonate-induced single-strand DNA damage...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28412323/single-cpg-site-methylation-controls-estrogen-receptor-gene-transcription-and-correlates-with-hormone-therapy-resistance
#8
Kouki Tsuboi, Takamasa Nagatomo, Tatsuyuki Gohno, Toru Higuchi, Shunta Sasaki, Natsu Fujiki, Masafumi Kurosumi, Hiroyuki Takei, Yuri Yamaguchi, Toshifumi Niwa, Shin-Ichi Hayashi
Hormone therapy is the most effective treatment for patients with estrogen receptor α-positive breast cancers. However, although resistance occurs during treatment in some cases and often reflects changed estrogen receptor α status, the relationship between changes in estrogen receptor α expression and resistance to therapy are poorly understood. In this study, we identified a mechanism for altered estrogen receptor α expression during disease progression and acquired hormone therapy resistance in aromatase inhibitor-resistant breast cancer cell lines...
April 12, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#9
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28401060/therapeutic-targeting-of-histone-modifications-in-adult-and-pediatric-high-grade-glioma
#10
REVIEW
Maria J Williams, Will G B Singleton, Stephen P Lowis, Karim Malik, Kathreena M Kurian
Recent exciting work partly through The Cancer Genome Atlas has implicated epigenetic mechanisms including histone modifications in the development of both pediatric and adult high-grade glioma (HGG). Histone lysine methylation has emerged as an important player in regulating gene expression and chromatin function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3 variants and the subject of posttranslational histone modifications, as it can be both methylated and acetylated. In pediatric HGG, two critical single-point mutations occur in the H3F3A gene encoding the regulatory histone variant H3...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28400196/association-of-rnaset2-gene-polymorphisms-with-decreased-expression-and-clinical-characteristics-of-severity-in-crohn-s-disease
#11
Rivkah Gonsky, Phillip Fleshner, Richard L Deem, Eva Biener-Ramanujan, Dalin Li, Alka A Potdar, Janine Bilsborough, Shaohong Yang, Dermot P B McGovern, Stephan R Targan
BACKGROUND & AIMS: Variants in the tumor necrosis factor superfamily member 15 gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory bowel diseases (IBD). TL1A affects expression of multiple cytokines to promote mucosal inflammation. Little is known about the TL1A-response pathways that regulate cytokine expression. We investigated T-cell gene expression patterns to determine the mechanisms by which TL1A regulates cytokine production, and whether these associate with outcomes of patients with Crohn's disease (CD)...
April 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28398335/high-coverage-methylation-data-of-a-gene-model-before-and-after-dna-damage-and-homologous-repair
#12
Antonio Pezone, Giusi Russo, Alfonso Tramontano, Ermanno Florio, Giovanni Scala, Rosaria Landi, Candida Zuchegna, Antonella Romano, Lorenzo Chiariotti, Mark T Muller, Max E Gottesman, Antonio Porcellini, Enrico V Avvedimento
Genome-wide methylation analysis is limited by its low coverage and the inability to detect single variants below 10%. Quantitative analysis provides accurate information on the extent of methylation of single CpG dinucleotide, but it does not measure the actual polymorphism of the methylation profiles of single molecules. To understand the polymorphism of DNA methylation and to decode the methylation signatures before and after DNA damage and repair, we have deep sequenced in bisulfite-treated DNA a reporter gene undergoing site-specific DNA damage and homologous repair...
April 11, 2017: Scientific Data
https://www.readbyqxmd.com/read/28395661/deepcpg-accurate-prediction-of-single-cell-dna-methylation-states-using-deep-learning
#13
Christof Angermueller, Heather J Lee, Wolf Reik, Oliver Stegle
Recent technological advances have enabled DNA methylation to be assayed at single-cell resolution. However, current protocols are limited by incomplete CpG coverage and hence methods to predict missing methylation states are critical to enable genome-wide analyses. We report DeepCpG, a computational approach based on deep neural networks to predict methylation states in single cells. We evaluate DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols. DeepCpG yields substantially more accurate predictions than previous methods...
April 11, 2017: Genome Biology
https://www.readbyqxmd.com/read/28395470/-an-investigation-of-trichloroethylene-induced-effects-on-histone-methylation-in-l-02-hepatic-cells
#14
R X Deng, X H Ren, J W Ruan, J Zheng, J C Zhong, W X Lu, X Q Zou, J J Liu
Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis...
April 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28391361/ultrastructural-localization-of-5-methylcytosine-on-dna-and-rna
#15
Irene Masiello, Marco Biggiogera
DNA methylation is the major epigenetic modification and it is involved in the negative regulation of gene expression. Its alteration can lead to neoplastic transformation. Several biomolecular approaches are nowadays used to study this modification on DNA, but also on RNA molecules, which are known to play a role in different biological processes. RNA methylation is one of the most common RNA modifications and 5-methylcytosine presence has recently been suggested in mRNA. However, an analysis of nucleic acid methylation at electron microscope is still lacking...
April 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28389961/chemotactic-behaviors-of-vibrio-cholerae-cells
#16
Ikuro Kawagishi, So-Ichiro Nishiyama
Vibrio cholerae, the causative agent of cholera, swims in aqueous environments with a single polar flagellum. In a spatial gradient of a chemical, the bacterium can migrate in "favorable" directions, a property that is termed chemotaxis. The chemotaxis of V. cholerae is not only critical for survival in various environments and but also is implicated in pathogenicity. In this chapter, we describe how to characterize the chemotactic behaviors of V. cholerae: these methods include swarm assay, temporal stimulation assay, capillary assay, and receptor methylation assay...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28388012/methylation-profiling-of-paediatric-pilocytic-astrocytoma-reveals-variants-specifically-associated-with-tumour-location-and-predictive-of-recurrence
#17
Alexandra Sexton-Oates, Andrew Dodgshun, Volker Hovestadt, David T W Jones, David M Ashley, Michael Sullivan, Duncan MacGregor, Richard Saffery
Childhood pilocytic astrocytomas (PA) are low grade tumours with an excellent prognosis. However, a minority, particularly those in surgically inaccessible locations, have poorer long term outcome. At present it is unclear whether anatomical location in isolation, or in combination with underlying biological variation, determines clinical behaviour. Here we have tested the utility of DNA methylation profiling to inform tumour biology and to predict behaviour in paediatric PA. Genome-wide DNA methylation profiles were generated for 117 paediatric PAs...
April 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28387156/mpk9-and-mpk12-function-in-sa-induced-stomatal-closure-in-arabidopsis-thaliana
#18
Md Atiqur Rahman Khokon, Mohammad Abdus Salam, Fabien Jammes, Wenxiu Ye, Mohammad Anowar Hossain, Eiji Okuma, Yoshimasa Nakamura, Izumi C Mori, June M Kwak, Yoshiyuki Murata
Salicylic acid (SA) induces stomatal closure sharing several components with abscisic acid (ABA) and methyl jasmonate (MeJA) signaling. We have previously shown that two guard cell-preferential mitogen-activated protein kinases (MAPKs), MPK9 and MPK12, positively regulate ABA signaling and MeJA signaling in Arabidopsis thaliana. In this study, we examined whether these two MAPKs are involved in SA-induced stomatal closure using genetic mutants and a pharmacological, MAPKK inhibitor. Salicylic acid induced stomatal closure in mpk9 and mpk12 single mutants but not in mpk9 mpk12 double mutants...
April 7, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28386905/butyrophilin-3a-btn3a-cd277-specific-antibody-20-1-differentially-activates-v%C3%AE-9v%C3%AE-2-tcr-clonotypes-and-interferes-with-phosphoantigen-activation
#19
Lisa Starick, Felipe Riano, Mohindar M Karunakaran, Volker Kunzmann, Jianqiang Li, Matthias Kreiss, Sabine Amslinger, Emmanuel Scotet, Daniel Olive, Gennaro De Libero, Thomas Herrmann
Phosphoantigens (PAg) like HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)-specific monoclonal antibody (mAb) 20.1 induce TCR-mediated activation of Vγ9Vδ2 T cells. Here, we compared murine reporter cells transduced with Vγ9Vδ2 TCRs G115, D1C55 and MOP for the activation in culture with human RAJI cells and PAgs or mAb 20.1 and its single chain derivative (sc). All transductants responded readily to PAg but only TCR MOP γ-chain-expressing cells responded to mAb/sc 20...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383772/aberrant-expression-of-mico1-and-mico1os-in-deceased-somatic-cell-nuclear-transfer-calves
#20
Guan-Nan Wang, Wen-Zhi Yang, Da Xu, Dong-Jie Li, Cui Zhang, Wei-Na Chen, Shi-Jie Li
Incomplete reprogramming of a donor nucleus following somatic cell nuclear transfer (SCNT) results in aberrant expression of developmentally important genes, and is the primary source of the phenotypic abnormalities observed in cloned animals. Expression of non-coding RNAs in the murine Dlk1-Dio3 imprinted domain was previously shown to correlate with the pluripotency of mouse induced pluripotent stem cells. In this study, we examined the transcription of the bovine orthologs from this locus, MICO1 (Maternal intergenic circadian oscillating 1) and MICO1OS (MICO1 opposite strand), in tissues from artificially inseminated and SCNT calves that died during the perinatal period...
April 6, 2017: Molecular Reproduction and Development
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