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https://www.readbyqxmd.com/read/29225167/adenovirus-infection-induces-hur-relocalization-to-facilitate-virus-replication
#1
Jumond P Jehung, Tetsuya Kitamura, Aya Yanagawa-Matsuda, Takeshi Kuroshima, Alam Towfik, Motoaki Yasuda, Hidehiko Sano, Yoshimasa Kitagawa, Kazuyuki Minowa, Masanobu Shindoh, Fumihiro Higashino
HuR is an RNA-binding protein of the embryonic lethal abnormal vision (ELAV) family, which binds to the AU-rich element (ARE) in the 3'-untranslated region (UTR) of certain mRNAs and is involved in the nucleo-cytoplasmic export and stabilization of ARE-mRNAs. The cytoplasmic relocalization of ARE-mRNAs with several proteins such as HuR and pp32 increases in cells transformed by the adenovirus oncogene product E4orf6. Additionally, these ARE-mRNAs were stabilized and acquired the potential to transform cells...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29224168/tet-assisted-bisulfite-sequencing-tab-seq
#2
Miao Yu, Dali Han, Gary C Hon, Chuan He
5-Hydroxymethylcytosine (5hmC) is a modified form of cytosine, which has recently been found in mammalian cells and tissues. 5hmC is derived from 5-methylcytosine (5mC) by Ten-eleven translocation (TET) family protein-mediated oxidation and may regulate gene expression. Numerous affinity-based profiling methods have been developed to help understand the exact function of 5hmC in the genome. However, these methods have a relatively low resolution (~100 bp) without quantitative information of the modification percentage on each site...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29210342/antibiotics-potentiating-potential-of-catharanthine-against-superbug-pseudomonas-aeruginosa
#3
Gaurav Raj Dwivedi, Rekha Tyagi, Sanchita Gupta, Shubhandra Tripathi, Sanghamitra Pati, Santosh K Srivastava, Mahendra P Darokar, Ashok Sharma
Multidrug resistance (MDR) put an alarming situation like preantibiotic era which compels us to invigorate the basic science of anti-infective chemotherapy. Hence the drug resistant genes/proteins were explored as promising drug targets. Keeping this thing in mind, proteome of Pseudomonas aeruginosa PA01 was explored, which resulted in the identification of tripartite protein complexes (MexA, MexB and OprM) as promising drug target for the screening of natural and synthetic inhibitors. The purpose of present investigation was to explore the drug resistance reversal potential mechanism of catharanthine isolated from the leaves of Catharanthus roseous...
December 6, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29207640/accurate-quantification-of-5-methylcytosine-5-hydroxymethylcytosine-5-formylcytosine-and-5-carboxylcytosine-in-genomic-dna-from-breast-cancer-by-chemical-derivatization-coupled-with-ultra-performance-liquid-chromatography-electrospray-quadrupole-time-of-flight
#4
Mengzhe Guo, Xiao Li, Liyan Zhang, Dantong Liu, Wencheng Du, Dengyang Yin, Nan Lyu, Guangyu Zhao, Cheng Guo, Daoquan Tang
The DNA demethylation pathway has been discovered to play a significant role in DNA epigenetics. This pathway removes the methyl group from cytosine, which is involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) proteins. Then, 5-hmC can be iteratively oxidized to generate 5-formylcytosine (5-foC) and 5-carboxylcytosine (5-caC). However, 5-hmC, 5-foC, and 5-caC are hardly detected due to their low content. In this study, we have developed a LC-HRMS method coupled with derivatization to accurately and simultaneously quantify 5-mC levels, along with its oxidation products in genomic DNA...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203910/tet-proteins-safeguard-bivalent-promoters-from-de-novo-methylation-in-human-embryonic-stem-cells
#5
Nipun Verma, Heng Pan, Louis C Doré, Abhijit Shukla, Qing V Li, Bobbie Pelham-Webb, Virginia Teijeiro, Federico González, Andrei Krivtsov, Chan-Jung Chang, Eirini P Papapetrou, Chuan He, Olivier Elemento, Danwei Huangfu
TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish owing to challenges in distinguishing global versus locus-specific effects. Here we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall corresponding decrease in gene expression in the undifferentiated state...
December 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29190698/profiles-of-a-broad-spectrum-of-epigenetic-dna-modifications-in-normal-and-malignant-human-cell-lines-proliferation-rate-is-not-the-major-factor-responsible-for-the-5-hydroxymethyl-2-deoxycytidine-level-in-cultured-cancerous-cell-lines
#6
Marek Foksinski, Ewelina Zarakowska, Daniel Gackowski, Magdalena Skonieczna, Karolina Gajda, Dorota Hudy, Anna Szpila, Karol Bialkowski, Marta Starczak, Anna Labejszo, Jaroslaw Czyz, Joanna Rzeszowska-Wolny, Ryszard Olinski
Active demethylation of 5-methylcytosine moiety in DNA occurs by its sequential oxidation to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, catalysed by enzymes of the Ten-Eleven Translocation family proteins (TETs 1, 2 and 3). Here we analyzed for the first time all the intermediate products of DNA demethylation pathway in the form of deoxynucleosides (5-methyl-2'-deoxycytidine, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine as well as 5-(hydroxymethyl)-2'-deoxyuridine) using automated isotope-dilution online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry...
2017: PloS One
https://www.readbyqxmd.com/read/29180630/atf4-overexpression-induces-early-onset-of-hyperlipidaemia-and-hepatic-steatosis-and-enhances-adipogenesis-in-zebrafish
#7
Kun-Yun Yeh, Chi-Yu Lai, Chiu-Ya Lin, Chia-Chun Hsu, Chung-Ping Lo, Guor Mour Her
Activating transcription factor 4 (ATF4) is constitutively expressed in a variety of tissues, and regulates several pathological features associated with metabolic diseases such as non-alcoholic fatty liver diseases (NAFLD) and obesity. However, the role of ATF4 in animal model systems is poorly understood. To investigate ATF4 functions in zebrafish, we conditionally expressed ATF4 proteins, using a Tet-off transgenic system. We observed early-onset hyperlipidaemia and liver steatosis in ATF4 transgenic zebrafish (ATs) without doxycycline treatment (ATs - Dox)...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180474/vitamin-c-sensitizes-melanoma-to-bet-inhibitors
#8
Gaofeng Wang, Sushmita Mustafi, Vladimir Camarena, Claude-Henry Volmar, Tyler C Huff, David W Sant, Shaun P Brothers, Zhao-Jun Liu, Claes Wahlestedt
Bromodomain and extra-terminal inhibitors (BETi) are promising cancer therapies, yet prominent side effects of BETi at effective doses have been reported in Phase I clinical trials. Here we screened a panel of small molecules targeting epigenetic modulators against human metastatic melanoma cells. Cells were pretreated with or without ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity to drugs. Top hits were structurally unrelated BETi including JQ1, I-BET151, CPI-203, and BI-2536...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#9
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#10
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#11
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29134746/fenofibrate-induced-ppar-alpha-expression-was-attenuated-by-oestrogen-receptor-alpha-overexpression-in-hep3b-cells
#12
Long-Bin Jeng, Bharath Kumar Velmurugan, Hsi-Hsien Hsu, Su-Ying Wen, Chia-Yao Shen, Chih-Hao Lin, Yueh-Min Lin, Ray-Jade Chen, Wei-Wen Kuo, Chih-Yang Huang
The physiological regulation of Oestrogen receptor α (ERα) and peroxisome proliferator-activated receptor alpha (PPARα) in Hepatocellular carcinoma (HCC) remains unknown. The present study we first treat the cells with fenofibrate and further investigated the possible mechanisms of 17β-estradiol (E2 ) and/or ERα on regulating PPARα expression. We also found higher PPARα expression in the tumor area than adjacent areas and subsequently compared PPARα expression in four different hepatic cancer cell lines...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29134547/detection-of-virulence-related-genes-in-lactococcus-garvieae-and-their-expression-in-response-to-different-conditions
#13
Giovanni Eraclio, Giovanni Ricci, Mattia Quattrini, Paolo Moroni, Maria Grazia Fortina
Lactococcus garvieae has emerged as an important zoonotic pathogen. However, information regarding mechanisms and factors related to its pathogenicity is lacking. In the present study, we investigated the distribution and functionality of genes related to virulence factors in L. garvieae strains isolated from different niches (diseased fish, humans, meat and dairy products, vegetables), using both post-genomic and genotypic analysis. Putative genes encoding hemolysin, fibronectin-binding protein, and penicillin acylase were detected in all analyzed genomes/strains...
November 13, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/29127112/reduced-expression-of-glutathione-s-transferase-%C3%AE-4-promotes-vascular-neointimal-hyperplasia-in-ckd
#14
Jinlong Luo, Guang Chen, Ming Liang, Aini Xie, Qingtian Li, Qunying Guo, Rajendra Sharma, Jizhong Cheng
Neointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)-mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs...
November 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29116071/-crispr-cas9-editing-based-modeling-of-hypoxia-in-renal-cancer-cells
#15
N A Zhigalova, S V Zhenilo, A V Artemov, E B Prokhortchouk
Uncontrolled growth in the cell mass of malignant tumors induces intensive angiogenesis. However, the demands of the cancer cells for nutrients and oxygen remain only partially met. Hypoxia is a process that accompanies malignant transformation and evokes changes in the DNA methylation profile in solid tumors. To a certain extent, these changes, including the hypermethylation of tumor suppressor gene promoters, are related to the decrease in the activity of Tet proteins under the conditions of oxygen and free radical deficit...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29108636/dynamic-expression-of-tet1-tet2-and-tet3-dioxygenases-in-mouse-and-human-placentas-throughout-gestation
#16
Joanna Rakoczy, Nisha Padmanabhan, Ada M Krzak, Jens Kieckbusch, Tereza Cindrova-Davies, Erica D Watson
INTRODUCTION: Throughout pregnancy, the placenta dynamically changes as trophoblast progenitors differentiate into mature trophoblast cell subtypes. This process is in part controlled by epigenetic regulation of DNA methylation leading to the inactivation of 'progenitor cell' genes and the activation of 'differentiation' genes. TET methylcytosine dioxygenases convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) during DNA demethylation events. Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider their role in trophoblast cell differentiation and function...
November 2017: Placenta
https://www.readbyqxmd.com/read/29106571/retrieval-induced-upregulation-of-tet3-in-pyramidal-neurons-of-the-dorsal-hippocampus-mediates-cocaine-associated-memory-reconsolidation
#17
Cao Liu, Xue Sun, Zhilin Wang, Qiumin Le, Peipei Liu, Changyou Jiang, Feifei Wang, Lan Ma
Background: Memory retrieval refers to re-exposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. Methods: We used cocaine-induced conditioned place preference (CPP) to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dHC...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29100757/an-uplc-ms-ms-method-for-quantifying-tetrandrine-and-its-metabolite-berbamine-in-human-blood-application-to-a-human-pharmacokinetic-study
#18
Guangyi Yang, Chenning Zhang, Pei Hu, Meiling Zhu, Ming Hu, Song Gao
Tetrandrine (TET) was approved by the China Food and Drug Administration (CFDA) for the treatment of silicosis. However, patients can't use this effective drug chronically due to side effects such as hypersomnia, asthenia, etc. The purpose of this study is to develop an UPLC-MS/MS method to quantify TET and its major metabolite and apply the method in a single dose human pharmacokinetic study. A Restek UItra BiPh column (100×2.1mm, 5μm) was used with acetonitrile and 0.1% formic acid in water as the mobile phases...
October 26, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29091188/inducibility-of-tn916-conjugative-transfer-in-enterococcus-faecalis-by-subinhibitory-concentrations-of-ribosome-targeting-antibiotics
#19
Hélène Scornec, Xavier Bellanger, Hélène Guilloteau, Guillaume Groshenry, Christophe Merlin
Background: Some antibiotics induce the dissemination of their own resistance genes by interfering with the regulation of specific mobile genetic elements. In Tn916, subinhibitory concentrations of tetracycline activate the transfer of the element through an anti-attenuation mechanism that relies on the Tet(M) resistance protein, itself encoded by the element. Objectives: This work explores the effects of a broad range of antibiotics on the transfer of Tn916 and for which the element does not provide any selective advantage...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#20
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
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