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https://www.readbyqxmd.com/read/28636816/impacts-of-the-mitochondrial-genome-on-the-relationship-of-long-term-ambient-fine-particle-exposure-with-blood-dna-methylation-age
#1
Jamaji Nwanaji-Enwerem, Elena Colicino, Lingzhen Dai, Akin Cayir, Marco Sanchez-Guerra, Hannah E Laue, Vy T Nguyen, Qian Di, Allan Just, Lifang Hou, Pantel Vokonas, Brent A Coull, Marc Weisskopf, Andrea Baccarelli, Joel Schwartz
The mitochondrial genome has long been implicated in age-related disease, but no studies have examined its role in the relationship of long-term fine particle (PM2.5) exposure and DNA methylation age (DNAm-age) - a novel measure of biological age. In this analysis based on 940 observations between 2000 and 2011 from 552 Normative Aging Study participants, we determined the roles of mitochondrial DNA haplogroup variation and mitochondrial genome abundance in the relationship of PM2.5 with DNAm-age. We used the GEOS-chem transport model to estimate address-specific, one-year PM2...
June 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28561023/expression-of-cd226-is-associated-to-but-not-required-for-nk-cell-education
#2
Arnika K Wagner, Nadir Kadri, Johanna Snäll, Petter Brodin, Susan Gilfillan, Marco Colonna, Günter Bernhardt, Petter Höglund, Klas Kärre, Benedict J Chambers
DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28558807/genome-wide-dna-methylation-at-birth-in-relation-to-in-utero-arsenic-exposure-and-the-associated-health-in-later-life
#3
Akhilesh Kaushal, Hongmei Zhang, Wilfried J J Karmaus, Todd M Everson, Carmen J Marsit, Margaret R Karagas, Shih-Fen Tsai, Hui-Ju Wen, Shu-Li Wang
BACKGROUND: In utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life. METHODS: Genome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure...
May 30, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28557603/genome-wide-methyl-seq-analysis-of-blood-brain-targets-of-glucocorticoid-exposure
#4
Fayaz Seifuddin, Gary Wand, Olivia Cox, Mehdi Pirooznia, Laura Moody, Xiaoju Yang, Jonathan Tai, Gretha Boersma, Kellie Tamashiro, Peter Zandi, Richard Lee
Chronic exposure to glucocorticoids (GCs) can lead to psychiatric complications through epigenetic mechanisms such as DNA methylation (DNAm). We sought to determine whether epigenetic changes in a peripheral tissue can serve as a surrogate for those in a relatively inaccessible tissue such as the brain. DNA extracted from the hippocampus and blood of mice treated with GCs or vehicle solution was assayed using a genome-wide DNAm platform (Methyl-Seq) to identify differentially methylated regions (DMRs) induced by GC treatment...
May 30, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28556790/dna-methylation-profiling-of-human-prefrontal-cortex-neurons-in-heroin-users-shows-significant-difference-between-genomic-contexts-of-hyper-and-hypomethylation-and-a-younger-epigenetic-age
#5
Alexey Kozlenkov, Andrew E Jaffe, Alisa Timashpolsky, Pasha Apontes, Sergei Rudchenko, Mihaela Barbu, William Byne, Yasmin L Hurd, Steve Horvath, Stella Dracheva
We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28). We identified 1298 differentially methylated CpG sites (DMSs) between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0...
May 30, 2017: Genes
https://www.readbyqxmd.com/read/28556588/effects-of-dna-methylation-on-progression-to-interstitial-fibrosis-and-tubular-atrophy-in-renal-allograft-biopsies-a-multi-omics-approach
#6
Sai Vineela Bontha, Daniel G Maluf, Kellie J Archer, Catherine I Dumur, Mikhail Dozmorov, Anne King, Enver Akalin, Thomas F Mueller, Lorenzo Gallon, Valeria R Mas
Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and non-immunological insults lead to interstitial fibrosis and tubular atrophy (IFTA) and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction...
May 28, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28523541/epigenetics-of-autism-spectrum-disorder
#7
Michelle T Siu, Rosanna Weksberg
Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28517981/a-systematic-review-of-studies-of-dna-methylation-in-the-context-of-a-weight-loss-intervention
#8
Lucia Aronica, A Joan Levine, Kevin Brennan, Jeffrey Mi, Christopher Gardner, Robert W Haile, Megan P Hitchins
AIM: Obesity results from the interaction of genetic and environmental factors, which may involve epigenetic mechanisms such as DNA methylation (DNAm). MATERIALS & METHODS: We have followed the PRISMA protocol to select studies that analyzed DNAm at baseline and end point of a weight loss intervention using either candidate-locus or genome-wide approaches. RESULTS: Six genes displayed weight loss associated DNAm across four out of nine genome-wide studies...
May 2017: Epigenomics
https://www.readbyqxmd.com/read/28515798/epigenome-wide-association-of-myocardial-infarction-with-dna-methylation-sites-at-loci-related-to-cardiovascular-disease
#9
Masahiro Nakatochi, Sahoko Ichihara, Ken Yamamoto, Keiko Naruse, Shigeki Yokota, Hiroyuki Asano, Tatsuaki Matsubara, Mitsuhiro Yokota
BACKGROUND: Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial infarction (MI), we performed an epigenome-wide association study for this condition in elderly Japanese subjects. A total of 192 case subjects with MI and 192 control subjects were recruited from hospital attendees and the general population, respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from whole blood were obtained by analysis with an Infinium HumanMethylation450 BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28503212/associations-between-maternal-risk-factors-of-adverse-pregnancy-and-birth-outcomes-and-the-offspring-epigenetic-clock-of-gestational-age-at-birth
#10
Polina Girchenko, Jari Lahti, Darina Czamara, Anna K Knight, Meaghan J Jones, Anna Suarez, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M Villa, Rebecca M Reynolds, Michael S Kobor, Alicia K Smith, Elisabeth B Binder, Katri Räikkönen
BACKGROUND: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28500316/establishment-of-a-strong-link-between-smoking-and-cancer-pathogenesis-through-dna-methylation-analysis
#11
Yunlong Ma, Ming D Li
Smoking is a well-documented risk factor in various cancers, especially lung cancer. In the current study, we tested the hypothesis that abnormal DNAm loci associated with smoking are enriched in genes and pathways that convey a risk of cancer by determining whether smoking-related methylated genes led to enrichment in cancer-related pathways. We analyzed two sets of smoking-related methylated genes from 28 studies originating from blood and buccal samples. By analyzing 320 methylated genes from 26 studies on blood samples (N = 17,675), we found 57 enriched pathways associated with different types of cancer (FDR < 0...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498033/development-and-characterization-of-novel-monoclonal-antibodies-against-human-dnam-1
#12
Genki Okumura, Fumie Abe, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8(+) T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human...
June 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28488432/photochemical-reactivity-of-dtpt3-a-crucial-nucleobase-derivative-in-the-development-of-semisynthetic-organisms
#13
Brennan Ashwood, Steffen Jockusch, Carlos E Crespo-Hernández
In 2017, the Romesberg group successfully developed the dTPT3·dNaM unnatural base pair to create a semisynthetic organism with enhanced genetic fidelity and the ability to store additional genetic information indefinitely. It is also desirable that the newly developed genetic material remains stable upon exposure to radiation. However, the photochemical properties of dTPT3 are presently unknown. In this contribution, excitation of dTPT3 with near-visible radiation is shown to efficiently populate a reactive triplet state in high yield and on a sub-1 ps time scale; a state that is able to survive for up to a few microseconds in aqueous solution...
May 12, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28486674/modifying-role-of-endothelial-function-gene-variants-on-the-association-of-long-term-pm2-5-exposure-with-blood-dna-methylation-age-the-va-normative-aging-study
#14
Jamaji C Nwanaji-Enwerem, Marie-Abele Bind, Lingzhen Dai, Youssef Oulhote, Elena Colicino, Qian Di, Allan C Just, Lifang Hou, Pantel Vokonas, Brent A Coull, Marc G Weisskopf, Andrea A Baccarelli, Joel D Schwartz
Recent studies have reported robust associations of long-term PM2.5 exposure with DNA methylation-based measures of aging; yet, the molecular implications of these relationships remain poorly understood. We evaluated if genetic variation in three biological pathways implicated in PM2.5-related disease - oxidative stress, endothelial function, and metal processing - could modify the effect of PM2.5 on DNAm-age, one prominent DNA methylation-based measure of biological age. This analysis was based on 552 individuals from the Normative Aging Study with at least one visit between 2000 and 2011 (n = 940 visits)...
May 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28486003/placental-lipoprotein-lipase-dna-methylation-alterations-are-associated-with-gestational-diabetes-and-body-composition-at-5%C3%A2-years-of-age
#15
Valérie Gagné-Ouellet, Andrée-Anne Houde, Simon-Pierre Guay, Patrice Perron, Daniel Gaudet, Renée Guérin, Jean-Patrice Baillargeon, Marie-France Hivert, Diane Brisson, Luigi Bouchard
Gestational diabetes mellitus (GDM) is associated with obesity in childhood. This suggests that consequences of in utero exposure to maternal hyperglycemia extend beyond the fetal development, possibly through epigenetic programming. The aims of this study were to assess whether placental DNA methylation (DNAm) marks were associated with maternal GDM status and to offspring body composition at 5 years old in a prospective birth cohort. DNAm levels were measured in the fetal side of the placenta in 66 samples (24 from GDM mothers) using bisDNA-pyrosequencing...
May 9, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28476540/epigenetic-and-transcriptional-modulation-of-wdr5-a-chromatin-remodeling-protein-in-huntington-s-disease-human-induced-pluripotent-stem-cell-hipsc-model
#16
Simona Baronchelli, Alberto La Spada, Aikaterini Ntai, Andrea Barbieri, Paola Conforti, Gloria Saccani Jotti, Serena Redaelli, Angela Bentivegna, Pasquale De Blasio, Ida Biunno
DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 differentially methylated regions (DMRs) at promoters in fully differentiated HD-hiPSCs. Subsequently, we focused on the methylation differences in a subcluster of genes related to Jumonji Domain Containing 3 (JMJD3), a demethylase that epigenetically regulates neuronal differentiation and activates neuronal progenitor associated genes, which are indispensable for neuronal fate acquisition...
May 2, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28475860/charge-and-kabuki-syndromes-gene-specific-dna-methylation-signatures-identify-epigenetic-mechanisms-linking-these-clinically-overlapping-conditions
#17
Darci T Butcher, Cheryl Cytrynbaum, Andrei L Turinsky, Michelle T Siu, Michal Inbar-Feigenberg, Roberto Mendoza-Londono, David Chitayat, Susan Walker, Jerry Machado, Oana Caluseriu, Lucie Dupuis, Daria Grafodatskaya, William Reardon, Brigitte Gilbert-Dussardier, Alain Verloes, Frederic Bilan, Jeff M Milunsky, Raveen Basran, Blake Papsin, Tracy L Stockley, Stephen W Scherer, Sanaa Choufani, Michael Brudno, Rosanna Weksberg
Epigenetic dysregulation has emerged as a recurring mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein 7 (CHD7(LOF)) and lysine (K) methyltransferase 2D (KMT2D(LOF)), respectively. Although these two syndromes are clinically distinct, there is significant phenotypic overlap. We therefore expected that epigenetically driven developmental pathways regulated by CHD7 and KMT2D would overlap and that DNA methylation (DNAm) alterations downstream of the mutations in these genes would identify common target genes, elucidating a mechanistic link between these two conditions, as well as specific target genes for each disorder...
May 4, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28456791/nk-cells-and-multiple-myeloma-associated-endothelial-cells-molecular-interactions-and-influence-of-il-27
#18
Alessandra Dondero, Beatrice Casu, Francesca Bellora, Angelo Vacca, Annunziata De Luisi, Maria Antonia Frassanito, Claudia Cantoni, Silvia Gaggero, Daniel Olive, Alessandro Moretta, Cristina Bottino, Roberta Castriconi
Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439722/dna-methylation-age-acceleration-is-associated-with-disease-duration-and-age-at-onset-in-c9orf72-patients
#19
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
#20
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
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