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https://www.readbyqxmd.com/read/29225347/accelerated-epigenetic-aging-and-mitochondrial-dna-copy-number-in-bipolar-disorder
#1
Gabriel R Fries, Isabelle E Bauer, Giselli Scaini, Mon-Ju Wu, Iram F Kazimi, Samira S Valvassori, Giovana Zunta-Soares, Consuelo Walss-Bass, Jair C Soares, Joao Quevedo
Bipolar disorder (BD) has been previously associated with accelerated aging; yet, the mechanisms underlying this association are largely unknown. The epigenetic clock has been increasingly recognized as a valuable aging marker, although its association with other biological clocks in BD patients and high-risk subjects, such as telomere length and mitochondrial DNA (mtDNA) copy number, has never been investigated. We included 22 patients with BD I, 16 siblings of BD patients, and 20 healthy controls in this analysis...
December 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29202043/epstein-barr-virus-induces-adhesion-receptor-cd226-dnam-1-expression-during-primary-b-cell-transformation-into-lymphoblastoid-cell-lines
#2
Lisa Grossman, Chris Chang, Joanne Dai, Pavel A Nikitin, Dereje D Jima, Sandeep S Dave, Micah A Luftig
Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that mediate cell-cell adhesion. We report that EBV potently induced expression of the adhesion molecule CD226, which is not normally expressed on B cells. We found that early after infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein expression...
November 2017: MSphere
https://www.readbyqxmd.com/read/29189780/a-semi-synthetic-organism-that-stores-and-retrieves-increased-genetic-information
#3
Yorke Zhang, Jerod L Ptacin, Emil C Fischer, Hans R Aerni, Carolina E Caffaro, Kristine San Jose, Aaron W Feldman, Court R Turner, Floyd E Romesberg
Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is the creation of semi-synthetic organisms whose DNA harbours two additional letters that form a third, unnatural base pair. Previous efforts to generate such semi-synthetic organisms culminated in the creation of a strain of Escherichia coli that, by virtue of a nucleoside triphosphate transporter from Phaeodactylum tricornutum, imports the requisite unnatural triphosphates from its medium and then uses them to replicate a plasmid containing the unnatural base pair dNaM-dTPT3...
November 29, 2017: Nature
https://www.readbyqxmd.com/read/29182664/differential-inhibitory-and-activating-nk-cell-receptor-levels-and-nk-nkt-like-cell-functionality-in-chronic-and-recovered-stages-of-chikungunya
#4
Subrat Thanapati, Mohini A Ganu, Anuradha S Tripathy
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29175600/forensic-dna-methylation-profiling-from-minimal-traces-how-low-can-we-go
#5
Jana Naue, Huub C J Hoefsloot, Ate D Kloosterman, Pernette J Verschure
Analysis of human DNA methylation (DNAm) can provide additional investigative leads in crime cases, e.g. the type of tissue or body fluid, the chronological age of an individual, and differentiation between identical twins. In contrast to the genetic profile, the DNAm level is not the same in every cell. At the single cell level, DNAm represents a binary event at a defined CpG site (methylated versus non-methylated). The DNAm level from a DNA extract however represents the average level of methylation of the CpG of interest of all molecules in the forensic sample...
November 13, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/29162165/epigenetic-correlates-of-neonatal-contact-in-humans
#6
Sarah R Moore, Lisa M McEwen, Jill Quirt, Alex Morin, Sarah M Mah, Ronald G Barr, W Thomas Boyce, Michael S Kobor
Animal models of early postnatal mother-infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4-5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29159506/a-longitudinal-study-of-dna-methylation-as-a-potential-mediator-of-age-related-diabetes-risk
#7
Crystal D Grant, Nadereh Jafari, Lifang Hou, Yun Li, James D Stewart, Guosheng Zhang, Archana Lamichhane, JoAnn E Manson, Andrea A Baccarelli, Eric A Whitsel, Karen N Conneely
DNA methylation (DNAm) has been found to show robust and widespread age-related changes across the genome. DNAm profiles from whole blood can be used to predict human aging rates with great accuracy. We sought to test whether DNAm-based predictions of age are related to phenotypes associated with type 2 diabetes (T2D), with the goal of identifying risk factors potentially mediated by DNAm. Our participants were 43 women enrolled in the Women's Health Initiative. We obtained methylation data via the Illumina 450K Methylation array on whole blood samples from participants at three timepoints, covering on average 16 years per participant...
November 20, 2017: GeroScience
https://www.readbyqxmd.com/read/29154208/characteristics-of-nk-cells-from-leukemic-microenvironment-in-mll-af9-induced-acute-myeloid-leukemia
#8
Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29139595/structure-and-electronic-properties-of-unnatural-base-pairs-role-of-dispersion-interactions
#9
Ayan Datta, Sk Jahiruddin, Nilangshu Mandal
Recent report of the success of unnatural base pairs (UBPs) like d5SICS-dNaM to be incorporated within the gene sequence and get replicated with DNA is an important milestone in synthetic biology. Followed by this, several other UBPs like dTPT3-dNaM, dTPT3-dFIMO, dTPT3-IMO, dTPT3-FEMO, FTPT3-NaM, FTPT3-FIMO, FTPT3-IMO, FTPT3-FEMO, have demonstrated similar or better retention and fidelity inside cell. Among these base pairs, dNaM-dTPT3 has been optimized to be a better fit inside a pAIO plasmid. Based on both implicit and explicit dispersion corrected density functional theory (DFT) calculations, we show that although the set of UBPs are significantly diverse in their elemental and structural configuration they do share a common trait of favoring a slipped parallel stacked dimer arrangement...
November 15, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rgnull-mice
#10
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34+ hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29118064/leukocyte-counts-based-on-dna-methylation-at-individual-cytosines
#11
Joana Frobel, Tanja Božić, Michael Lenz, Peter Uciechowski, Yang Han, Reinhild Herwartz, Klaus Strathmann, Susanne Isfort, Jens Panse, André Esser, Carina Birkhofer, Uwe Gerstenmaier, Thomas Kraus, Lothar Rink, Steffen Koschmieder, Wolfgang Wagner
BACKGROUND: White blood cell counts are routinely measured with automated hematology analyzers, by flow cytometry, or by manual counting. Here, we introduce an alternative approach based on DNA methylation (DNAm) at individual CG dinucleotides (CpGs). METHODS: We identified candidate CpGs that were nonmethylated in specific leukocyte subsets. DNAm levels (ranging from 0% to 100%) were analyzed by pyrosequencing and implemented into deconvolution algorithms to determine the relative composition of leukocytes...
November 8, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29106301/mirna-processing-gene-polymorphisms-blood-dna-methylation-age-and-long-term-ambient-pm2-5-exposure-in-elderly-men
#12
Jamaji C Nwanaji-Enwerem, Elena Colicino, Lingzhen Dai, Qian Di, Allan C Just, Lifang Hou, Pantel Vokonas, Immaculata De Vivo, Bernardo Lemos, Quan Lu, Marc G Weisskopf, Andrea A Baccarelli, Joel D Schwartz
AIM: We tested whether genetic variation in miRNA processing genes modified the association of PM2.5 with DNA methylation (DNAm) age. PATIENTS & METHODS: We conducted a repeated measures study based on 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n = 940 visits). Address-level 1-year PM2.5 exposures were estimated using the GEOS-chem model. DNAm-age and a panel of 14 SNPs in miRNA processing genes were measured from participant blood samples...
November 6, 2017: Epigenomics
https://www.readbyqxmd.com/read/29092053/mining-dna-methylation-alterations-towards-a-classification-of-placental-pathologies
#13
Samantha L Wilson, Katherine Leavey, Brian Cox, Wendy P Robinson
Placental health is a key component to a successful pregnancy. Placental insufficiency (PI), inadequate nutrient delivery to the fetus, is associated with preeclampsia (PE), a maternal hypertensive disorder, and intrauterine growth restriction (IUGR), pathologically poor fetal growth. PI is more common in early-onset PE (EOPE) than late-onset PE (LOPE). However, the relationship between these disorders remains unclear. While DNA methylation (DNAm) alterations have been identified in PE and IUGR, these entities can overlap and few studies have analyzed them separately...
October 30, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29083167/qm-and-qm-mm-studies-on-excited-state-relaxation-mechanisms-of-unnatural-bases-in-vacuo-and-base-pairs-in-dna
#14
Qian Wang, Xiao-Ying Xie, Juan Han, Ganglong Cui
Semisynthetic alphabet can potentially increase the genetic information stored in DNA through the formation of unusual base pairs such as d5SICS:dNaM. However, recent experiments show that near-visible-light irradiation on the d5SICS and dNaM chromophores could lead to genetic mutations and damages. Until now, their photophysical mechanisms remain elusive. Herein, we have employed MS-CASPT2//CASSCF and QM(MS-CASPT2//CASSCF)/MM methods to explore the spectroscopic properties and excited-state relaxation mechanisms of d5SICS, dNaM, and d5SICS:dNaM in DNA...
November 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29082545/testing-for-the-indirect-effect-under-the-null-for-genome-wide-mediation-analyses
#15
Richard Barfield, Jincheng Shen, Allan C Just, Pantel S Vokonas, Joel Schwartz, Andrea A Baccarelli, Tyler J VanderWeele, Xihong Lin
Mediation analysis helps researchers assess whether part or all of an exposure's effect on an outcome is due to an intermediate variable. The indirect effect can help in designing interventions on the mediator as opposed to the exposure and better understanding the outcome's mechanisms. Mediation analysis has seen increased use in genome-wide epidemiological studies to test for an exposure of interest being mediated through a genomic measure such as gene expression or DNA methylation (DNAm). Testing for the indirect effect is challenged by the fact that the null hypothesis is composite...
December 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/29074605/allogeneic-human-double-negative-t-cells-as-a-novel-immunotherapy-for-acute-myeloid-leukemia-and-its-underlying-mechanisms
#16
Jong Bok Lee, Mark D Minden, Weihsu C Chen, Elena Streck, Branson Chen, Hyeonjeong Kang, Andrea Arruda, Dalam Ly, Sandy D Der, Sohyeong Kang, Paulina Achita, Cheryl D'Souza, Yueyang Li, Richard W Childs, John E Dick, Li Zhang
PURPOSE: To explore the potential of ex vivo expanded healthy donor derived allogeneic CD4 and CD8 double negative cells (DNTs) as a novel cellular immunotherapy for leukemia patients. EXPERIMENTAL DESIGN: Clinical grade DNTs from peripheral blood of healthy donors were expanded and their anti-leukemic activity and safety were examined using flow-cytometry based in vitro killing assays and xenograft models against AML patient blasts and healthy donor-derived hematopoietic cells...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29066808/cross-tissue-integration-of-genetic-and-epigenetic-data-offers-insight-into-autism-spectrum-disorder
#17
Shan V Andrews, Shannon E Ellis, Kelly M Bakulski, Brooke Sheppard, Lisa A Croen, Irva Hertz-Picciotto, Craig J Newschaffer, Andrew P Feinberg, Dan E Arking, Christine Ladd-Acosta, M Daniele Fallin
Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29061445/amelioration-of-nk-cell-function-driven-by-v%C3%AE-24-invariant-nkt-cell-activation-in-multiple-myeloma
#18
Tomonori Iyoda, Satoru Yamasaki, Michihiro Hidaka, Fumio Kawano, Yu Abe, Kenshi Suzuki, Norimitsu Kadowaki, Kanako Shimizu, Shin-Ichiro Fujii
NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells...
October 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29028809/nasal-dna-methylation-differentiates-corticosteroid-treatment-response-in-pediatric-asthma-a-pilot-study
#19
Xue Zhang, Jocelyn M Biagini Myers, Veda K Yadagiri, Ashley Ulm, Xiaoting Chen, Matthew T Weirauch, Gurjit K Khurana Hershey, Hong Ji
BACKGROUND: Treatment response to systemic corticosteroid in asthmatic children is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to identify DNA methylation (DNAm) changes responsive to steroid, and DNAm biomarkers that distinguish treatment response. MATERIALS AND METHODS: We followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for asthma exacerbation. Based on whether they met discharge criteria in ≤24 hours, participants were grouped into good and poor responders to steroid treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28988914/dna-methylation-age-is-not-accelerated-in-brain-or-blood-of-subjects-with-schizophrenia
#20
Brandon C McKinney, Huang Lin, Ying Ding, David A Lewis, Robert A Sweet
Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die ~20years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce "DNAm age", an estimate of biological age with advantages over existing measures...
October 5, 2017: Schizophrenia Research
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