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https://www.readbyqxmd.com/read/28213474/a-bayesian-approach-for-analysis-of-whole-genome-bisulphite-sequencing-data-identifies-disease-associated-changes-in-dna-methylation
#1
Owen J L Rackham, Sarah R Langley, Thomas Oates, Eleni Vradi, Nathan Harmston, Prashant K Srivastava, Jacques Behmoaras, Petros Dellaportas, Leonardo Bottolo, Enrico Petretto
DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate...
February 17, 2017: Genetics
https://www.readbyqxmd.com/read/28212554/afb1-hepatocarcinogenesis-is-via-lipid-peroxidation-that-inhibits-dna-repair-sensitizes-mutation-susceptibility-and-induces-aldehyde-dna-adducts-at-p53-mutational-hotspot-codon-249
#2
Mao-Wen Weng, Hyun-Wook Lee, Bongkun Choi, Hsiang-Tsui Wang, Yu Hu, Manju Mehta, Dhimant Desai, Shantu Amin, Yi Zheng, Moon-Shong Tang
Aflatoxin B1 (AFB1) contamination in the food chain is a major cause of hepatocellular carcinoma (HCC). More than 60% of AFB1 related HCC carry p53 codon 249 mutations but the causal mechanism remains unclear. We found that 1) AFB1 induces two types of DNA adducts in human hepatocytes, AFB1-8,9-epoxide-deoxyguanosine (AFB1-E-dG) induced by AFB1-E and cyclic α-methyl-γ-hydroxy-1,N2-propano-dG (meth-OH-PdG) induced by lipid peroxidation generated acetaldehyde (Acet) and crotonaldehyde (Cro); 2) the level of meth-OH-PdG is >30 fold higher than the level of AFB1-E-dG; 3) AFB1, Acet, and Cro, but not AFB1-E, preferentially induce DNA damage at codon 249; 4) methylation at -CpG- sites enhances meth-OH-PdG formation at codon 249; and 5) repair of meth-OH-PdG at codon 249 is poor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212312/genome-wide-prediction-of-dna-methylation-using-dna-composition-and-sequence-complexity-in-human
#3
Chengchao Wu, Shixin Yao, Xinghao Li, Chujia Chen, Xuehai Hu
DNA methylation plays a significant role in transcriptional regulation by repressing activity. Change of the DNA methylation level is an important factor affecting the expression of target genes and downstream phenotypes. Because current experimental technologies can only assay a small proportion of CpG sites in the human genome, it is urgent to develop reliable computational models for predicting genome-wide DNA methylation. Here, we proposed a novel algorithm that accurately extracted sequence complexity features (seven features) and developed a support-vector-machine-based prediction model with integration of the reported DNA composition features (trinucleotide frequency and GC content, 65 features) by utilizing the methylation profiles of embryonic stem cells in human...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28211912/dna-methylation-map-in-circulating-leukocytes-mirrors-subcutaneous-adipose-tissue-methylation-pattern-a-genome-wide-analysis-from-non-obese-and-obese-patients
#4
A B Crujeiras, A Diaz-Lagares, J Sandoval, F I Milagro, S Navas-Carretero, M C Carreira, A Gomez, D Hervas, M P Monteiro, F F Casanueva, M Esteller, J A Martinez
The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#5
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211355/correction-cpg-blocks-immunosuppression-by-myeloid-derived-suppressor-cells-in-tumor-bearing-mice
#6
(no author information available yet)
No abstract text is available yet for this article.
February 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28209276/the-aahks-clinical-research-award-what-are-the-costs-of-knee-osteoarthritis-in-the-year-prior-to-total-knee-arthroplasty
#7
Nicholas A Bedard, Spencer B Dowdle, Christopher A Anthony, David E DeMik, Michael A McHugh, Kevin J Bozic, John J Callaghan
BACKGROUND: Despite American Academy of Orthopaedic Surgeons Clinical Practice Guidelines (CPGs) related to the non-arthroplasty management of osteoarthritis (OA) of the knee, non-recommended treatments remain in common use. We sought to determine the costs associated with non-arthroplasty management of knee OA in the year prior to total knee arthroplasty (TKA) and stratify them by CPG recommendation status. METHODS: The Humana database was reviewed from 2007 to 2015 for primary TKA patients...
January 18, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28208084/hypomethylation-of-tissue-factor-pathway-inhibitor-2-in-human-placenta-of-preeclampsia
#8
Xirong Xiao, Xiang Tao, Yongxiang Wang, Lisha Zhu, Yunzhen Ye, Haiyan Liu, Qiongjie Zhou, Xiaotian Li, Yu Xiong
OBJECTIVES: To investigate the expression, DNA methylation status and its regulatory mechanism of tissue factor pathway inhibitor 2 (TFPI-2) in human placenta tissues of preeclampsia (PE). MATERIAL AND METHODS: We studied the mRNA and protein expression and the promoter methylation levels of TFPI-2 in the PE placentas compared with those in the normal pregnant (NP) women. Quantitative real-time polymerase chain reaction, immunohistochemistry, western blot, and Sequenom MassARRAY were used for placenta tissue detection...
February 8, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#9
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28207251/cross-linked-micellar-spherical-nucleic-acids-from-thermoresponsive-templates
#10
Resham J Banga, Brian Meckes, Suguna P Narayan, Anthony J Sprangers, SonBinh T Nguyen, Chad A Mirkin
A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles followed by chemical cross-linking and subsequent removal of non-crosslinked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization making them effective TLR-9 immunomodulatory agents...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28205556/hrgfish-a-database-of-hypoxia-responsive-genes-in-fishes
#11
Iliyas Rashid, Naresh Sahebrao Nagpure, Prachi Srivastava, Ravindra Kumar, Ajey Kumar Pathak, Mahender Singh, Basdeo Kushwaha
Several studies have highlighted the changes in the gene expression due to the hypoxia response in fishes, but the systematic organization of the information and the analytical platform for such genes are lacking. In the present study, an attempt was made to develop a database of hypoxia responsive genes in fishes (HRGFish), integrated with analytical tools, using LAMPP technology. Genes reported in hypoxia response for fishes were compiled through literature survey and the database presently covers 818 gene sequences and 35 gene types from 38 fishes...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203120/international-lessons-in-new-methods-for-grading-and-integrating-cost-effectiveness-evidence-into-clinical-practice-guidelines
#12
REVIEW
Kathryn M Antioch, Michael F Drummond, Louis W Niessen, Hindrik Vondeling
Economic evidence is influential in health technology assessment world-wide. Clinical Practice Guidelines (CPG) can enable economists to include economic information on health care provision. Application of economic evidence in CPGs, and its integration into clinical practice and national decision making is hampered by objections from professions, paucity of economic evidence or lack of policy commitment. The use of state-of-art economic methodologies will improve this. Economic evidence can be graded by 'checklists' to establish the best evidence for decision making given methodological rigor...
2017: Cost Effectiveness and Resource Allocation: C/E
https://www.readbyqxmd.com/read/28202002/viral-e6-is-overexpressed-via-high-viral-load-in-invasive-cervical-cancer-with-episomal-hpv16
#13
Die Hong, Jia Liu, Ying Hu, Xiaonan Lu, Baohua Li, Yang Li, Dongxiao Hu, Weiguo Lu, Xing Xie, Xiaodong Cheng
BACKGROUND: The integration of HR-HPV genome into host DNA is regarded as a key step for the development of cervical cancer. However, HR-HPV genome indeed exists as episome except for integrant. It may be alternative mechanisms in episome-associated carcinogenesis, although, by which HPV 16 episome induces cervical carcinogenesis is unclear now. METHODS: Ninety-three invasive cervical cancer tissues with HPV16 positive were collected. Viral physical status was calculated from comparing E2 to E6-copies and detection of viral load was made with realtime-PCR using copy numbers of E6...
February 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28198981/toll-like-receptor-agonists-porphyromonas-gingivalis-lps-and-cpg-differentially-regulate-il-10-competency-and-frequencies-of-mouse-b10-cells
#14
Zhiqiang Liu, Yang Hu, Pei Yu, Mei Lin, Grace Huang, Toshihisa Kawai, Martin Taubman, Zuomin Wang, Han Xiaozhe
Objective: This study is to determine the effects of P. gingivalis LPS and CpG on B10 cell expansion and IL-10 competency in vitro. Material and Methods: Spleen B cells were isolated from C57BL/6J mice with or without formalin-fixed P. gingivalis immunization. B cells were cultured for 48 hours under the following conditions: CD40L, CD40L+LPS, CD40L+CpG, and CD40L+LPS+CpG in the presence or absence of fixed P. gingivalis. Percentages of CD1dhiCD5+ B cells were measured by flow cytometry...
January 2017: Journal of Applied Oral Science: Revista FOB
https://www.readbyqxmd.com/read/28198392/coffee-consumption-is-associated-with-dna-methylation-levels-of-human-blood
#15
Yu-Hsuan Chuang, Austin Quach, Devin Absher, Themistocles Assimes, Steve Horvath, Beate Ritz
Beneficial health effects have been attributed to coffee consumption, but it is not yet known whether epigenetics may have a role in this process. Here we associate epigenome-wide DNA methylation levels to habitual coffee consumption from two studies with blood (2100 and 215 participants), and one with saliva samples (256 participants). Adjusting for age, gender, and blood cell composition, one CpG (cg21566642 near ALPPL2) surpassed genome-wide significance (P=3.7 × 10(-10)) and from among 10 additional CpGs significant at P≤5...
February 15, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28196748/up-regulation-of-cx3cr1-on-tonsillar-cd8-positive-cells-in-patients-with-iga-nephropathy
#16
Ryuki Otaka, Miki Takahara, Seigo Ueda, Toshihiro Nagato, Kan Kishibe, Kenichiro Nomura, Akihiro Katada, Tatsuya Hayashi, Yasuaki Harabuchi
Although tonsillectomy are used as therapeutic options to prevent chronic renal failure in IgA nephropathy (IgAN) patients, the relationship between IgAN and tonsils is not fully proved by basic research. Recently, circulating CX3CR1-positive cells were reportedly involved in promoting hematuria in patients with IgAN. In this study, we focused on the expression of CX3CR1 in tonsillar mononuclear cells in IgAN patients. Immunohistological analysis revealed greater distribution of CX3CR1-positive cells in the inter-follicular area of tonsils in IgAN patients than in non-IgAN patients...
February 11, 2017: Human Immunology
https://www.readbyqxmd.com/read/28194813/microrna-191-acts-as-a-tumor-promoter-by-modulating-the-tet1-p53-pathway-in-intrahepatic-cholangiocarcinoma
#17
Hao Li, Zun-Qiang Zhou, Zhang-Ru Yang, Da-Nian Tong, Jiao Guan, Bao-Jie Shi, Jia Nie, Xian-Ting Ding, Bin Li, Guang-Wen Zhou, Zheng-Yun Zhang
: Current treatment of intrahepatic cholangiocarcinoma (ICC) remains ineffective because knowledge of ICC carcinogenesis is unclear. Increasing evidence suggests that microRNAs (miRNAs), including miRNA-191, play an important role in tumorigenesis, but expression and biological functions of miRNA-191 in ICC remain to be established. This study aimed to investigate the functions and underlying mechanisms of miRNA-191 in ICC. ICC miRNA profiles were generated in 5 pairs of ICC and matched to normal bile duct tissues by next-generation sequencing technology; ICC miRNA profiles were verified in 18 pairs of ICC tissues and normal bile duct tissues by quantitative reverse transcription PCR (qRT-PCR)...
February 14, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194238/epigenome-wide-association-study-ewas-on-lipids-the-rotterdam-study
#18
Kim V E Braun, Klodian Dhana, Paul S de Vries, Trudy Voortman, Joyce B J van Meurs, Andre G Uitterlinden, Albert Hofman, Frank B Hu, Oscar H Franco, Abbas Dehghan
BACKGROUND: DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28193856/contribution-of-epigenetic-mechanisms-to-variation-in-cancer-risk-among-tissues
#19
Michael Klutstein, Joshua Moss, Tommy Kaplan, Howard Cedar
Recently, it was suggested that tissue variation in cancer risk originates from differences in the number of stem-cell divisions underlying each tissue, leading to different mutation loads. We show that this variation is also correlated with the degree of aberrant CpG island DNA methylation in normal cells. Methylation accumulates during aging in a subset of molecules, suggesting that the epigenetic landscape within a founder-cell population may contribute to tumor formation.
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193703/methylation-in-the-matrix-metalloproteinase-2-gene-is-associated-with-cerebral-ischemic-stroke
#20
Hsiu-Fen Lin, Edward Hsi, Ling-Chun Huang, Yi-Chu Liao, Suh-Hang H Juo, Ruey-Tay Lin
Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites...
February 13, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
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