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https://www.readbyqxmd.com/read/29236683/effector-cd8-t-cells-dedifferentiate-into-long-lived-memory-cells
#1
Ben Youngblood, J Scott Hale, Haydn T Kissick, Eunseon Ahn, Xiaojin Xu, Andreas Wieland, Koichi Araki, Erin E West, Hazem E Ghoneim, Yiping Fan, Pranay Dogra, Carl W Davis, Bogumila T Konieczny, Rustom Antia, Xiaodong Cheng, Rafi Ahmed
Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29234621/neonatal-exposure-to-6-n-propyl-thiouracil-an-anti-thyroid-drug-alters-expression-of-hepatic-dna-methyltransferases-methyl-cpg-binding-proteins-gadd45a-p53-and-pcna-in-adult-male-rats
#2
Suresh Kumar Bunker, Jagneshwar Dandapat, Gagan B N Chainy, Sunil Kumar Sahoo, Prabhat Kumar Nayak
Background: Neonatal 6-n-propyl-2-thiouracil (PTU) exposure to male rats is reported to impair liver function in adulthood. However, the mechanism by which the drug impairs liver function is not well known. Objectives: The objectives of the study were to investigate the effects of neonatal exposure of PTU on the expression of DNA methyltransferases (DNMTs), methyl-DNA binding proteins (MBDs), Gadd45a, p53, and proliferating cell nuclear antigen (PCNA) in adult rat liver...
November 2017: European Thyroid Journal
https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#3
Wenji Li, Zheng-Yuan Su, Yue Guo, Chengyue Zhang, RenYi Wu, Linbo Gao, Xi Zheng, Zhi-Yun Du, Kun Zhang, Ah-Ng Kong
The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydrothiopyran-4-one (F10) and (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways...
December 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29227812/overexpression-of-arginase-1-is-linked-to-dnmt3a-and-tet2-mutations-in-lower-grade-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia
#4
A H Cull, D Mahendru, B Snetsinger, D Good, K Tyryshkin, A Chesney, Z Ghorab, M Reis, R Buckstein, R A Wells, M J Rauh
Immune dysregulation is a common feature of myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), particularly in early stages. However, the genetic basis remains poorly understood. We recently reported that macrophages from mice deficient in tet methylcytosine dioxygenase 2 (Tet2), a model of MDS/CMML, are hyperinflammatory and have increased expression of arginase 1 (Arg1). In macrophages and myeloid derived suppressor cells (MDSCs) expression of Arg1 contributes to T-cell suppression and immune evasion by L-arginine depletion, in the setting of chronic inflammation and cancer...
December 6, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#5
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29209431/combining-cytogenetic-and-epigenetic-approaches-in-chronic-lymphocytic-leukemia-improves-prognosis-prediction-for-patients-with-isolated-13q-deletion
#6
Cristina Bagacean, Christelle Le Dantec, Christian Berthou, Adrian Tempescul, Hussam Saad, Anne Bordron, Mihnea Zdrenghea, Victor Cristea, Nathalie Douet-Guilbert, Yves Renaudineau
Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints])...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29209239/genetic-biomarkers-on-age-related-cognitive-decline
#7
REVIEW
Chieh-Hsin Lin, Eugene Lin, Hsien-Yuan Lane
With ever-increasing elder populations, age-related cognitive decline, which is characterized as a gradual decline in cognitive capacity in the aging process, has turned out to be a mammoth public health concern. Since genetic information has become increasingly important to explore the biological mechanisms of cognitive decline, the search for genetic biomarkers of cognitive aging has received much attention. There is growing evidence that single-nucleotide polymorphisms (SNPs) within the ADAMTS9, BDNF, CASS4, COMT, CR1, DNMT3A, DTNBP1, REST, SRR, TOMM40, circadian clock, and Alzheimer's diseases-associated genes may contribute to susceptibility to cognitive aging...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29203905/rainbow-trout-exposed-to-benzo-a-pyrene-yields-conserved-microrna-binding-sites-in-dna-methyltransferases-across-500-million-years-of-evolution
#8
Christopher Kuc, Daniel J Richard, Samantha Johnson, Leslie Bragg, Mark R Servos, Andrew C Doxey, Paul M Craig
The objective of this study was to examine the regulation of DNA methylation following acute (24 h) and prolonged (14 d) exposure to low (1 ng/L) and high (10 ng/L) benzo[a]pyrene. However, with the recent release of the rainbow trout genome, we were able to conduct a more detailed analysis regarding the regulation of the enzymes involved in DNA methylation; DNA methyltransferases (DNMTs). Bioinformatic approaches were used to identify candidate microRNA (miRNA) that potentially bind to the DNMT1 and DNMT3a 3'UTR...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29195897/an-inflammatory-environment-containing-tnf%C3%AE-favors-tet2-mutant-clonal-hematopoiesis
#9
Samuel O Abegunde, Rena Buckstein, Richard A Wells, Michael J Rauh
Clonal hematopoiesis of aging and indeterminate potential (ARCH or CHIP), driven mainly by mutations in DNMT3A and TET2, is an emerging public health issue, affecting at least 10-15% of adults older than 65 years. CHIP is associated with increased risks of de novo and therapy-related hematological neoplasms and serves as a reservoir for leukemic relapse. CHIP is also associated with increased all-cause mortality and risk of cardio-metabolic disease. The latter association may be explained, at least in part, by the effects of inactivating mutations in TET2 on progeny macrophages...
November 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29193057/prognostic-utility-of-six-mutated-genes-for-older-patients-with-acute-myeloid-leukemia
#10
Jinghan Wang, Zhixin Ma, Qinrong Wang, Qi Guo, Jiansong Huang, Wenjuan Yu, Huanping Wang, Jingwen Huang, Yang Washington Shao, Suning Chen, Jie Jin
Approximately 50% of older patients with acute myeloid leukemia (AML) do not obtain chromosomal abnormalities as an effective risk-stratification, and present cytogenetically normal AML (CN-AML). In order to develop a reliable prediction model for stratifying the risk of these elderly patients, we conducted a study with a discovery and validation design. As a result, we found the top 6 mutated genes in the discovery cohort of 26 case by the whole exome sequencing, and verified as recurrent mutations in the large cohort of 329 patients by sanger sequencing...
November 29, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29188605/-analysis-of-prognosis-of-acute-myeloid-leukemia-patients-based-on-genetic-mutations
#11
Jinning Shi, Yu Zhu, Ming Hong, Huihui Zhao, Jianping Mao, Hui Jin, Wenjing Zhang, Ting Zhang, Yongchao Ma, Yaoyu Chen, Sixuan Qian, Jianyong Li, Chun Qiao
OBJECTIVE: To correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations. METHODS: Somatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients...
December 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29181075/mgmt-promoter-methylation-as-a-potential-prognostic-marker-for-acute-leukemia
#12
Dominika Sobieszkoda, Joanna Czech, Natalia Gablo, Marta Kopanska, Jacek Tabarkiewicz, Agnieszka Kolacinska, Tadeusz Robak, Izabela Zawlik
Introduction: It has been proved that genetic and epigenetic changes play a significant role in the development and progression of acute leukemia. The aim of our study was to evaluate the frequency and prognostic implications of genetic and epigenetic alterations in p15, MGMT, DNMT3A and TP53 genes in acute leukemias. Material and methods: We included in the study 59 patients with acute leukemia. Evaluation of TP53 and DNMT3A mutations was performed using sequencing analysis and PCR-RFLP, respectively...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29177435/de-novo-mutations-implicate-novel-genes-in-systemic-lupus-erythematosus
#13
Venu Pullabhatla, Amy L Roberts, Myles J Lewis, Daniele Mauro, David L Morris, Christopher A Odhams, Philip Tombleson, Ulrika Liljedahl, Simon Vyse, Michael A Simpson, Sascha Sauer, Emanuele de Rinaldis, Ann-Christine Syvänen, Timothy J Vyse
The omnigenic model of complex disease stipulates that the majority of the heritability will be explained by the effects of common variation on genes in the periphery of core disease pathways. Rare variant associations, expected to explain far less of the heritability, may be enriched in core disease genes and thus will be instrumental in the understanding of complex disease pathogenesis and their potential therapeutic targets. Here, using complementary whole-exome sequencing, high-density imputation, and in vitro cellular assays, we identify candidate core genes in the pathogenesis of Systemic Lupus Erythematosus (SLE)...
November 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29172276/flt3-itd-npm1-and-dnmt3a-gene-mutations-and-risk-factors-in-normal-karyotype-acute-myeloid-leukemia-and-myelodysplastic-syndrome-patients-in-upper-northern-thailand
#14
Piyanan Mevatee, Adisak Tantiworawit, Patrinee Traisathit, Chaniporn Puaninta, Umnat Mevatee, Sirinda Angsuchawan, Kanokkan Bumroongkit
Objective: Approximately 40-45% of AML and MDS patients have a cytogenetically normal karyotype (CN-AML and CN-MDS). The frequency and types of gene mutations in these cases may differ among various populations. The objective of this study was to identify frequencies and types of FLT3-ITD, NPM1, and DNMT3A mutations, and associations of them with clinical data and risk factors in CN-AML and CN-MDS cases in upper Northern Thailand. Methods: Bone marrow samples of 40 CN-AML and 60 CN-MDS patients were analyzed for gene mutations by direct sequencing...
November 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29170626/role-of-microrna-143-in-nerve-injury-induced-upregulation-of-dnmt3a-expression-in-primary-sensory-neurons
#15
Bo Xu, Jing Cao, Jun Zhang, Shushan Jia, Shaogen Wu, Kai Mo, Guihua Wei, Lingli Liang, Xuerong Miao, Alex Bekker, Yuan-Xiang Tao
Peripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated genes (such as Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral nerve injury is still elusive. We reported here that peripheral nerve injury caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143 expression in injured DRG...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29167013/bovine-oviductal-and-uterine-fluid-support-in-vitro-embryo-development
#16
Meriem Hamdi, Ricaurte Lopera-Vasquez, Veronica Maillo, Maria Jesus Sanchez-Calabuig, Carolina Núnez, Alfonso Gutierrez-Adan, Dimitrios Rizos
In order to mimic the maternal oviductal environment, we evaluated the effect of oviductal fluid (OF) and/or uterine fluid (UF) supplementation on in vitro embryo development and quality. In vitro-produced zygotes were cultured with 1.25% OF from Day 1 to Day 4 after insemination (OF group), 1.25% OF from Day 1 to Day 4 followed by 1.25% UF from Day 4 to Day 9 (OF+UF group) or 1.25% UF only from Day 4 to Day 9 (UF group). Control groups were cultured in the presence of synthetic oviduct fluid (SOF) supplemented with 3mgmL-1 bovine serum albumin (BSA) or 5% fetal calf serum (FCS)...
November 23, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29166738/-expression-characteristics-and-prognosis-significance-of-mirna-181a-in-acute-myeloid-leukemia-with-normal-karyotype
#17
X X Zhuang, Q L Ma, H P Wang, M X Yu, X Li, H T Meng, W J Yu, C J Jin, L S You, J Jin
Objective: To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance. Methods: The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29165010/dnmt3a-co-mutation-is-required-for-flt3-itd-as-an-adverse-prognostic-indicator-in-intermediate-risk-cytogenetic-group-aml
#18
Juan Ma, Jennifer Dunlap, Aleksandra Paliga, Elie Traer, Richard Press, Lisong Shen, Guang Fan
This single institution cohort study of 132 AML patients investigated the clinical implications of co-mutations detected with a 42-gene NGS panel. In the intermediate-risk cytogenetic group, FLT3-ITD is an adverse prognostic indicator only in the presence of a DNMT3A co-mutation, regardless of NPM1 mutation status. In the absence of a concomitant DNMT3A mutation, there was no significant difference in overall survival between FLT3-ITD positive and FLT3-ITD negative patients. Furthermore, mutation analysis on post-induction specimens showed that residual FLT3-ITD and/or DNMT3A mutations were associated with a high frequency of therapy resistance or relapse in AML...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29164635/influence-of-genetic-variants-of-idh1-idh2-tet2-and-dnmt3a-on-cytarabine-cytotoxicity-in-different-populations
#19
Y Wang, J K Lamba
WHAT IS KNOWN AND OBJECTIVE: Cytarabine (ara-C) is the mainstay of treatment for acute myeloid leukaemia. Resistance and toxicity are common reasons for its treatment failure. Genetic variants of susceptibility genes may be involved in resistance and toxicity to ara-C. This study is aimed to explore the association between influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in European and/or African populations. METHODS: HapMap cell lines derived from European descent (CEU) and African descent (YRI) were exposed to ara-C at different concentrations (1, 5, 40 and 80 μmol/L)...
November 21, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29164502/superovulation-alters-dna-methyltransferase-protein-expression-in-mouse-oocytes-and-early-embryos
#20
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
PURPOSE: DNA methylation is an epigenetic mechanism that plays critical roles during mammalian oocyte and preimplantation embryo development. It is achieved by adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites using DNA methyltransferase (DNMT) enzymes for de novo and maintenance methylation processes. DNMT1, DNMT3A, and DNMT3B play important roles in establishing methylation of developmentally related genes in oocytes and early embryos...
November 22, 2017: Journal of Assisted Reproduction and Genetics
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