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https://www.readbyqxmd.com/read/28439722/dna-methylation-age-acceleration-is-associated-with-disease-duration-and-age-at-onset-in-c9orf72-patients
#1
Ming Zhang, Maria Carmela Tartaglia, Danielle Moreno, Christine Sato, Paul McKeever, Anna Weichert, Julia Keith, Janice Robertson, Lorne Zinman, Ekaterina Rogaeva
The repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. C9orf72 patients present with a wide range in disease duration and age of onset. The strongest risk factor for both syndromes is aging, which was linked to DNA methylation (DNAm) age based on the cumulative assessment of the methylation levels of 353 CpGs included on the genome-wide 450k BeadChip. DNAm age may reflect biological age better than chronological age. We conducted a genome-wide blood DNA methylation study of 46 unrelated C9orf72 patients...
April 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28428831/cord-blood-hematopoietic-cells-from-preterm-infants-display-altered-dna-methylation-patterns
#2
Olivia M de Goede, Pascal M Lavoie, Wendy P Robinson
BACKGROUND: Premature infants are highly vulnerable to infection. This is partly attributable to the preterm immune system, which differs from that of the term neonate in cell composition and function. Multiple studies have found differential DNA methylation (DNAm) between preterm and term infants' cord blood; however, interpretation of these studies is limited by the confounding factor of blood cell composition. This study evaluates the epigenetic impact of preterm birth in isolated hematopoietic cell populations, reducing the concern of cell composition differences...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28405496/il-12-il-15-and-il-18-pre-activated-nk-cells-target-resistant-t-cell-acute-lymphoblastic-leukemia-and-delay-leukemia-development-in-vivo
#3
Margherita Boieri, Aina Ulvmoen, Amanda Sudworth, Clare Lendrem, Matthew Collin, Anne M Dickinson, Lise Kveberg, Marit Inngjerdingen
NK cells have shown promise in therapy of hematological cancers, in particular against acute myeloid leukemia. In contrast, the more NK cell-resistant acute lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, and we hypothesized that pre-activation of NK cells could overcome this resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28394373/structural-and-dynamical-instability-of-dna-caused-by-high-occurrence-of-d5sics-and-dnam-unnatural-nucleotides
#4
Rodrigo Galindo-Murillo, Joaquín Barroso-Flores
In vivo inclusion of unnatural base pairs (UBPs) into functional DNA was recently reported for compounds 2,6-dimethyl-2H-isoquiniline-1-thione (d5SICS, X) and 2-methoxy-3-methylnaphthalene (dNaM, Y) in a modified E. coli strand, for which high-fidelity replication was observed. Yet, little is known about possible genetic consequences they have in largely substituted DNA. Using a converged microsecond long molecular dynamics (MD) simulation of the sequences 5'-GCGCAAXTTGCGC-3' and 5'-GCGCXAXTXGCGC-3', where X represents the UBP, we show that in the system with only a single XY UBP pair present, the global RMS deviation from canonical B-DNA in our control simulations is ∼3 Å and a fully converged ensemble is achieved within 2 µs...
April 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28387568/non-linear-patterns-in-age-related-dna-methylation-may-reflect-cd4-t-cell-differentiation
#5
Nicholas D Johnson, Howard W Wiener, Alicia K Smith, Shota Nishitani, Devin M Absher, Donna K Arnett, Stella Aslibekyan, Karen N Conneely
DNA methylation (DNAm) is an important epigenetic process involved in the regulation of gene expression. While many studies have identified thousands of loci associated with age, few have differentiated between linear and non-linear DNAm trends with age. Non-linear trends could indicate early- or late-life gene regulatory processes. Using data from the Illumina 450K array on 336 human peripheral blood samples, we identified 21 CpG sites that associated with age (P<1.03E-7) and exhibited changing rates of DNAm change with age (P<1...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28364215/dna-methylation-age-is-elevated-in-breast-tissue-of-healthy-women
#6
Mary E Sehl, Jill E Henry, Anna Maria Storniolo, Patricia A Ganz, Steve Horvath
BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference...
March 31, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28337208/natural-killer-cell-development-and-maturation-revisited-possible-implications-of-a-novel-distinct-lin-cd34-dnam-1-bright-cxcr4-cell-progenitor
#7
Federica Bozzano, Francesco Marras, Andrea De Maria
Since the first description of natural killer (NK) cells, the view on their role in innate immunity has evolved considerably. In addition to first-line defense against transformed and pathogen-infected autologous cells, NK cells contribute to modulate adaptive immune responses and in some cases acquire specialized functions, including exhausted, adaptive, and decidual NK cells. NK cells derive from CD34(+) progenitors, in vivo and in vitro; however, it is unclear whether the high phenotype diversity in vivo may be generated from these precursors alone...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28303888/dna-methylation-signatures-in-peripheral-blood-strongly-predict-all-cause-mortality
#8
Yan Zhang, Rory Wilson, Jonathan Heiss, Lutz P Breitling, Kai-Uwe Saum, Ben Schöttker, Bernd Holleczek, Melanie Waldenberger, Annette Peters, Hermann Brenner
DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28292535/maintained-memory-in-aging-is-associated-with-young-epigenetic-age
#9
Sofie Degerman, Maria Josefsson, Annelie Nordin Adolfsson, Sigrid Wennstedt, Mattias Landfors, Zahra Haider, Sara Pudas, Magnus Hultdin, Lars Nyberg, Rolf Adolfsson
Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden...
February 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28284819/associations-between-long-term-exposure-to-pm2-5-component-species-and-blood-dna-methylation-age-in-the-elderly-the-va-normative-aging-study
#10
Jamaji C Nwanaji-Enwerem, Lingzhen Dai, Elena Colicino, Youssef Oulhote, Qian Di, Itai Kloog, Allan C Just, Lifang Hou, Pantel Vokonas, Andrea A Baccarelli, Marc G Weisskopf, Joel D Schwartz
BACKGROUND: Long-term PM2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5 on human health. OBJECTIVE: We assessed the relationship of major PM2.5 component species (ammonium, elemental carbon, organic carbon, nitrate, and sulfate) with Horvath and Hannum DNA methylation (DNAm) age, two DNA methylation-based predictors of chronological age...
May 2017: Environment International
https://www.readbyqxmd.com/read/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#11
Alessandra Soriani, Cristiana Borrelli, Biancamaria Ricci, Rosa Molfetta, Alessandra Zingoni, Cinzia Fionda, Silvia Carnevale, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Giuseppe La Regina, Erica Di Cesare, Patrizia Lavia, Romano Silvestri, Rossella Paolini, Marco Cippitelli, Angela Santoni
The mechanisms that regulate the expression of the NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established that their expression is finely regulated at transcriptional, post-transcriptional and post-translational level, and involve numerous stress pathways depending on the type of ligand, stressor, and cell context. We show that treatment of Multiple Myeloma (MM) cells with sub-lethal doses of Vincristine (VCR), an anticancer drug that inhibits the assembly of microtubules, stimulates the expression of NKG2D and DNAM-1 activating ligands, rendering these cells more susceptible to NK cell-mediated killing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195572/dna-methylation-as-a-putative-mechanism-for-reduced-dendritic-spine-density-in-the-superior-temporal-gyrus-of-subjects-with-schizophrenia
#12
B McKinney, Y Ding, D A Lewis, R A Sweet
Reduced dendritic spine density (DSD) in cortical layer 3 of the superior temporal gyrus (STG), and multiple other brain regions, is consistently observed in postmortem studies of schizophrenia (SZ). Elucidating the molecular mechanisms of this intermediate phenotype holds promise for understanding SZ pathophysiology, identifying SZ treatment targets and developing animal models. DNA methylation (DNAm), the addition of a methyl group to a cytosine nucleotide, regulates gene transcription and is a strong candidate for such a mechanism...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28168006/individual-cpg-sites-that-are-associated-with-age-and-life-expectancy-become-hypomethylated-upon-aging
#13
Yan Zhang, Jan Hapala, Hermann Brenner, Wolfgang Wagner
BACKGROUND: There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age-and the deviation of chronological and predicted age (∆age) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28165855/genome-wide-dna-methylation-associations-with-spontaneous-preterm-birth-in-us-blacks-findings-in-maternal-and-cord-blood-samples
#14
Xiumei Hong, Ben Sherwood, Christine Ladd-Acosta, Shouneng Peng, Hongkai Ji, Ke Hao, Irina Burd, Tami R Bartell, Guoying Wang, Hui-Ju Tsai, Xin Liu, Yuelong Ji, Anastacia Wahl, Deanna Caruso, Aviva Lee-Parritz, Barry Zuckerman, Xiaobin Wang
Preterm birth (PTB) affects one in six U.S. Black babies. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort...
February 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28125511/dna-methylation-patterns-in-cord-blood-of-neonates-across-gestational-age-association-with-cell-type-proportions
#15
Susan M Braid, Kwame Okrah, Amol Shetty, Hector Corrada Bravo
BACKGROUND: A statistical methodology is available to estimate the proportion of cell types (cellular heterogeneity) in adult whole blood specimens used in epigenome-wide association studies (EWAS). However, there is no methodology to estimate the proportion of cell types in umbilical cord blood (also a heterogeneous tissue) used in EWAS. OBJECTIVES: The objectives of this study were to determine whether differences in DNA methylation (DNAm) patterns in umbilical cord blood are the result of blood cell type proportion changes that typically occur across gestational age and to demonstrate the effect of cell type proportion confounding by comparing preterm infants exposed and not exposed to antenatal steroids...
March 2017: Nursing Research
https://www.readbyqxmd.com/read/28115716/a-semisynthetic-organism-engineered-for-the-stable-expansion-of-the-genetic-alphabet
#16
Yorke Zhang, Brian M Lamb, Aaron W Feldman, Anne Xiaozhou Zhou, Thomas Lavergne, Lingjun Li, Floyd E Romesberg
All natural organisms store genetic information in a four-letter, two-base-pair genetic alphabet. The expansion of the genetic alphabet with two synthetic unnatural nucleotides that selectively pair to form an unnatural base pair (UBP) would increase the information storage potential of DNA, and semisynthetic organisms (SSOs) that stably harbor this expanded alphabet would thereby have the potential to store and retrieve increased information. Toward this goal, we previously reported that Escherichia coli grown in the presence of the unnatural nucleoside triphosphates dNaMTP and d5SICSTP, and provided with the means to import them via expression of a plasmid-borne nucleoside triphosphate transporter, replicates DNA containing a single dNaM-d5SICS UBP...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#17
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28073928/evidence-of-epigenetic-admixture-in-the-colombian-population
#18
Konrad Rawlik, Amy Rowlatt, María Carolina Sanabria-Salas, Gustavo Hernández-Suárez, Martha Lucía Serrano López, Jovanny Zabaleta, Albert Tenesa
DNA methylation (DNAm) measured in lymphoblastoid cell lines has been repeatedly demonstrated to differ between various human populations. Due to the role that DNAm plays in controlling gene expression, these differences could significantly contribute to ethnic phenotypic differences. However, because previous studies have compared distinct ethnic groups where genetic and environmental context are confounded, their relative contribution to phenotypic differences between ethnicities remains unclear. Using DNAm assayed in whole blood and colorectal tissue of 132 admixed individuals from Colombia, we identified sites where differential DNAm levels were associated with the local ancestral genetic context...
February 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28035916/the-paired-receptors-tigit-and-dnam-1-as-targets-for-therapeutic-antibodies
#19
Natan Stein, Pinchas Tsukerman, Ofer Mandelboim
One of the most exciting fields in modern medicine is immunotherapy, treatment which looks to harness the power of the immune system to fight disease. A particularly effective strategy uses antibodies designed to influence the activity levels of the immune system. Here we look at two receptors - TIGIT and DNAM-1 - which bind the same ligands but have opposite effects on immune cells, earning them the label `paired receptors'. Importantly, natural killer cells and cytotoxic T cells express both of these receptors, and in certain cases their effector functions are dictated by TIGIT or DNAM-1 signaling...
December 23, 2016: Human Antibodies
https://www.readbyqxmd.com/read/27996157/high-pesticide-exposure-events-and-dna-methylation-among-pesticide-applicators-in-the-agricultural-health-study
#20
Jennifer A Rusiecki, Laura E Beane Freeman, Matthew R Bonner, Melannie Alexander, Ligong Chen, Gabriella Andreotti, Kathryn H Barry, Lee E Moore, Hyang-Min Byun, Freya Kamel, Michael Alavanja, Jane A Hoppin, Andrea Baccarelli
Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime...
December 20, 2016: Environmental and Molecular Mutagenesis
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