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https://www.readbyqxmd.com/read/28796508/in-vivo-structure-activity-relationships-and-optimization-of-an-unnatural-base-pair-for-replication-in-a-semi-synthetic-organism
#1
Aaron W Feldman, Floyd E Romesberg
In an effort to expand the genetic alphabet and create semi-synthetic organisms (SSOs) that store and retrieve increased information, we have developed the unnatural base pairs (UBPs) dNaM and d5SICS or dTPT3 (dNaM-d5SICS and dNaM-dTPT3). The UBPs form based on hydrophobic and packing forces, as opposed to complementary hydrogen bonding, and while they are both retained within the in vivo environment of an Escherichia coli SSO, their development was based on structure-activity relationship (SAR) data generated in vitro...
August 10, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28770015/maternal-blood-contamination-of-collected-cord-blood-can-be-identified-using-dna-methylation-at-three-cpgs
#2
Alexander M Morin, Evan Gatev, Lisa M McEwen, Julia L MacIsaac, David T S Lin, Nastassja Koen, Darina Czamara, Katri Räikkönen, Heather J Zar, Karestan Koenen, Dan J Stein, Michael S Kobor, Meaghan J Jones
BACKGROUND: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28765218/dengue-virus-infected-dendritic-cells-but-not-monocytes-activate-natural-killer-cells-through-a-contact-dependent-mechanism-involving-adhesion-molecules
#3
Vivian Vasconcelos Costa, Weijian Ye, Qingfeng Chen, Mauro Martins Teixeira, Peter Preiser, Eng Eong Ooi, Jianzhu Chen
Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28747766/dna-methylation-signatures-of-chronic-alcohol-dependence-in-purified-cd3-t-cells-of-patients-undergoing-alcohol-treatment
#4
Christof Brückmann, Sumaiya A Islam, Julia L MacIsaac, Alexander M Morin, Kathrin N Karle, Adriana Di Santo, Richard Wüst, Immanuel Lang, Anil Batra, Michael S Kobor, Vanessa Nieratschker
Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play an important role in alcohol dependence. In the present study, we analysed genome-wide DNAm profiles of purified CD3(+) T-cells from pre- and post-treatment alcohol dependent patients, as well as closely matched healthy controls. We identified 59 differentially methylated CpG sites comparing patients prior to treatment with healthy controls and were able to confirm 8 of those sites in additional analyses for differentially methylated regions...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743252/quantification-of-tumour-evolution-and-heterogeneity-via-bayesian-epiallele-detection
#5
James E Barrett, Andrew Feber, Javier Herrero, Miljana Tanic, Gareth A Wilson, Charles Swanton, Stephan Beck
BACKGROUND: Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment. It is increasingly recognised that the study of DNA methylation (DNAm) patterns along the genome - so-called 'epialleles' - offers greater insight into epigenetic dynamics than conventional analyses which examine DNAm marks individually. RESULTS: We have developed a Bayesian model to infer which epialleles are present in multiple regions of the same tumour...
July 25, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28736860/annual-research-review-dna-methylation-as-a-mediator-in-the-association-between-risk-exposure-and-child-and-adolescent-psychopathology
#6
REVIEW
Edward D Barker, Esther Walton, Charlotte A M Cecil
BACKGROUND: DNA methylation (DNAm) is a potential mechanism for propagating the effects of environmental exposures on child and adolescent mental health. In recent years, this field has experienced steady growth. METHODS: We provide a strategic review of the current child and adolescent literature to evaluate evidence for a mediating role of DNAm in the link between environmental risks and psychopathological outcomes, with a focus on internalising and externalising difficulties...
July 24, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28731985/accelerated-dna-methylation-age-associations-with-ptsd-and-mortality
#7
Erika J Wolf, Mark W Logue, Tawni B Stoop, Steven A Schichman, Annjanette Stone, Naomi Sadeh, Jasmeet P Hayes, Mark W Miller
OBJECTIVE: Recently-developed indices of cellular age based on DNA methylation (DNAm) data, referred to as DNAm age, are being used to study factors that influence the rate of aging and the health correlates of these metrics of the epigenetic clock. This study evaluated associations between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and accelerated versus decelerated DNAm age among military veterans. We also examined if accelerated DNAm age predicted mortality over the course of a 6...
July 20, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#8
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28675549/visible-light-mediated-excited-state-relaxation-in-semi-synthetic-genetic-alphabet-d5sics-and-dnam
#9
Kalishankar Bhattacharyya, Ayan Datta
The excited state dynamics of an unnatural base pair (UBP) d5SICS/dNaM were investigated by accurate ab-initio calculations. Time-dependent density functional and high-level multireference calculations (MS-CASPT2) were performed to elucidate the excitation of this UBP and its excited state relaxation mechanism. After excitation to the bright state S2 (ππ*), it decays to the S1 state and then undergoes efficient intersystem crossing to the triplet manifold. The presence of sulfur atom in d5SICS leads to strong spin-orbit coupling (SOC) and a small energy gap that facilitates intersystem crossing from S1 (ns π*) to T2 (ππ*) followed by internal conversion to T1 state...
July 4, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28673994/social-and-physical-environments-early-in-development-predict-dna-methylation-of-inflammatory-genes-in-young-adulthood
#10
Thomas W McDade, Calen Ryan, Meaghan J Jones, Julia L MacIsaac, Alexander M Morin, Jess M Meyer, Judith B Borja, Gregory E Miller, Michael S Kobor, Christopher W Kuzawa
Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28654252/synthetic-biology-parts-for-the-storage-of-increased-genetic-information-in-cells
#11
Sydney E Morris, Aaron W Feldman, Floyd E Romesberg
To bestow cells with novel forms and functions, the goal of synthetic biology, we have developed the unnatural nucleoside triphosphates dNaMTP and dTPT3TP, which form an unnatural base pair (UBP) and expand the genetic alphabet. While the UBP may be retained in the DNA of a living cell, its retention is sequence-dependent. We now report a steady-state kinetic characterization of the rate with which the Klenow fragment of E. coli DNA polymerase I synthesizes the UBP and its mispairs in a variety of sequence contexts...
June 27, 2017: ACS Synthetic Biology
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
#12
Jamaji C Nwanaji-Enwerem, Elena Colicino, Lingzhen Dai, Akin Cayir, Marco Sanchez-Guerra, Hannah E Laue, Vy T Nguyen, Qian Di, Allan C Just, Lifang Hou, Pantel Vokonas, Brent A Coull, Marc G Weisskopf, Andrea A Baccarelli, Joel D 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...
July 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28561023/expression-of-cd226-is-associated-to-but-not-required-for-nk-cell-education
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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