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Yan Zhao, Pengcheng Liu, Junyong Wang, Xirong Xiao, Xiangzhou Meng, Yunhui Zhang
BACKGROUND: In utero polybrominated diphenyl ethers (PBDEs) exposure has been associated with adverse fetal growth. Alterations in placental DNA methylation might mediate those adverse effects. OBJECTIVES: To examine the associations between in utero PBDEs exposure and DNA methylation in human placenta. METHODS: Eighty apparently healthy mother-newborn pairs delivering at the Second Affiliated Hospital of Wenzhou Medical College were enrolled in this study...
October 18, 2016: Environment International
Hiromi Shiratori, Carmen Feinweber, Claudia Knothe, Jörn Lötsch, Dominique Thomas, Gerd Geisslinger, Michael J Parnham, Eduard Resch
DNA methylation is a major regulatory process of gene transcription, and aberrant DNA methylation is associated with various diseases including cancer. Many compounds have been reported to modify DNA methylation states. Despite increasing interest in the clinical application of drugs with epigenetic effects, and the use of diagnostic markers for genome-wide hypomethylation in cancer, large-scale screening systems to measure the effects of drugs on DNA methylation are limited. In this study, we improved the previously established fluorescence polarization-based global DNA methylation assay so that it is more suitable for application to human genomic DNA...
2016: PloS One
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
Isaac Zilinsky, Detlev Erdmann, Oren Weissman, Niels Hammer, Mircea-Constantin Sora, Thilo L Schenck, Sebastian Cotofana
The anatomical basis for auricular flaps used in multiple aesthetic and reconstructive procedures is currently based on a random distribution of the underlying arterial network. However, recent findings reveal a systematic pattern as opposed to the present concepts. Therefore, we designed this study to assess the arterial vascular pattern of the auricle in order to provide reliable data about the vascular map required for surgical interventions. Sixteen human auricles from eight body donors (five females/three males, 84...
October 11, 2016: Journal of Anatomy
Atma M Ivancevic, R Daniel Kortschak, Terry Bertozzi, David L Adelson
LINE-1 (L1) retrotransposons are dynamic elements. They have the potential to cause great genomic change because of their ability to 'jump' around the genome and amplify themselves, resulting in the duplication and rearrangement of regulatory DNA. Active L1, in particular, are often thought of as tightly constrained, homologous and ubiquitous elements with well-characterised domain organisation. For the past 30 years, model organisms have been used to define L1s as 6-8kb sequences containing a 5'-UTR, two open reading frames working harmoniously in cis, and a 3'-UTR with a polyA tail...
October 3, 2016: Genome Biology and Evolution
Luna Gargani, Rosa Sicari, Mauro Raciti, Luca Serasini, Mirko Passera, Claudia Torino, Krzysztof Letachowicz, Robert Ekart, Danilo Fliser, Adrian Covic, Olga Balafa, Aristeidis Stavroulopoulos, Ziad A Massy, Enrico Fiaccadori, Alberto Caiazza, Thomas Bachelet, Itzchak Slotki, Linda Shavit, Alberto Martinez-Castelao, Marie-Jeanne Coudert-Krier, Patrick Rossignol, Thomas Daniel Kraemer, Thierry Hannedouche, Vincenzo Panichi, Andrzej Wiecek, Giuseppe Pontoriero, Pantelis Sarafidis, Marian Klinger, Radovan Hojs, Sarah Seiler-Mußler, Fabio Lizzi, Mihai Onofriescu, Fotis Zarzoulas, Rocco Tripepi, Francesca Mallamaci, Giovanni Tripepi, Eugenio Picano, Gérard Michel London, Carmine Zoccali
Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme...
September 26, 2016: Nephrology, Dialysis, Transplantation
Stefanie Atsem, Juliane Reichenbach, Ramya Potabattula, Marcus Dittrich, Caroline Nava, Christel Depienne, Lena Böhm, Simone Rost, Thomas Hahn, Martin Schorsch, Thomas Haaf, Nady El Hajj
Children of older fathers carry an increased risk for developing autism and other disorders. To elucidate the underlying mechanisms, we investigated the correlation of sperm DNA methylation with paternal age and its impact on the epigenome of the offspring. Methylation levels of 9 candidate genes and LINE-1 repeats were quantified by bisulfite pyrosequencing in sperm of 162 donors and 191 cord blood of resulting children (conceived by IVF/ICSI with the same sperm samples). Four genes showed a significant negative correlation between sperm methylation and paternal age...
September 23, 2016: Human Molecular Genetics
Elisa Orecchini, Margherita Doria, Ambra Antonioni, Silvia Galardi, Silvia Anna Ciafrè, Loredana Frassinelli, Carmine Mancone, Claudia Montaldo, Marco Tripodi, Alessandro Michienzi
Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosines to inosines in double-stranded RNAs. ADAR1 was demonstrated to be functional on different viruses exerting either antiviral or proviral effects. Concerning HIV-1, several studies showed that ADAR1 favors viral replication. The aim of this study was to investigate the composition of the ADAR1 ribonucleoprotein complex during HIV-1 expression. By using a dual-tag affinity purification procedure in cells expressing HIV-1 followed by mass spectrometry analysis, we identified 14 non-ribosomal ADAR1-interacting proteins, most of which are novel...
September 21, 2016: Nucleic Acids Research
Hiroaki Kijima, Shin Yamada, Natsuo Konishi, Hitoshi Kubota, Hiroshi Tazawa, Takayuki Tani, Norio Suzuki, Keiji Kamo, Yoshihiko Okudera, Ken Sasaki, Tetsuya Kawano, Naohisa Miyakoshi, Yoichi Shimada
PURPOSE: In femoral trochanteric fractures, fractures whose fracture lines extend to the basal neck or to the subtrochanteric part have high instability. Area classification can identify such instable fractures. The best choices of internal fixators for femoral trochanteric fractures were investigated according to area classification. METHODS: Femoral trochanteric fractures were investigated with respect to area classification. In area classification, the proximal femur is divided into 4 areas with 3 boundary lines: Line-1 is the center of the neck; Line-2 is the border between the neck and the trochanteric zone; and Line-3 links the inferior borders of the greater and lesser trochanters...
2016: SpringerPlus
Simone Jueliger, John Lyons, Sara Cannito, Illar Pata, Pille Pata, Marianna Shkolnaya, Oriana Lo Re, Marion Peyrou, Francesc Villarroya, Valerio Pazienza, Francesca Rappa, Francesco Cappello, Mohammad Azab, Pietro Taverna, Manlio Vinciguerra
Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine...
August 11, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Saichon Chaiwongwatanakul, Pattamawadee Yanatatsaneejit, Sissades Tongsima, Apiwat Mutirangura, Viroj Boonyaratanakornkit
Long interspersed elements-1s (LINE-1s) are dispersed all over the human genome. There is evidence that hypomethylation of LINE-1s and levels of sex steroids regulate gene expression leading to cancer development. Here, we compared mRNA levels of genes containing an intragenic LINE-1 in breast cancer cells treated with various sex steroids from Gene Expression Omnibus (GEO), with the gene expression database using chi-square analysis ( We evaluated whether sex steroids influence expression of genes containing an intragenic LINE-1...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Liang Liu, Qi-Meng Yin, Xian-Wen Zhang, Wei Wang, Xiao-Yun Dong, Xin Yan, Rong Hu
Three new biphenanthrenes, Liparisphenanthrenes A-C (1-3), along with three known ones were obtained from the ethanolic extract of Liparis nervosa (Orchidaceae) by bioactivity-guided fractionation. Their structures were elucidated on the basis of extensive spectroscopic analysis. All the compounds obtained were tested in vitro for cytotoxic activities against stomach (HGC-27) and colon (HT-29) cancer cell lines. 1, 4 and 5 showed potent cytotoxicities to HGC-27 cell line with IC50 values of 8.21-9.95μmol/L, and 1 and 5 also exhibited potent cytotoxic activities to HT-29 cell line with IC50 values of 8...
September 15, 2016: Fitoterapia
Thomas J Meyer, Ulrike Held, Kimberly A Nevonen, Sabine Klawitter, Thomas Pirzer, Lucia Carbone, Gerald G Schumann
LAVA ( L: INE- A: lu- V: NTR- A: lu-like) elements comprise a family of non-autonomous, composite, non-LTR retrotransposons specific to gibbons and may have played a role in the evolution of this lineage. A full-length LAVA element consists of portions of repeats found in most primate genomes: CT-rich, Alu-like, and VNTR regions from the SVA retrotransposon, and portions of the AluSz and L1ME5 elements. To evaluate whether the gibbon genome currently harbors functional LAVA elements capable of mobilization by the endogenous LINE-1 (L1) protein machinery and which LAVA components are important for retrotransposition, we established a trans-mobilization assay in HeLa cells...
September 15, 2016: Genome Biology and Evolution
Kanako Kojima-Kita, Satomi Kuramochi-Miyagawa, Ippei Nagamori, Narumi Ogonuki, Atsuo Ogura, Hidetoshi Hasuwa, Takashi Akazawa, Norimitsu Inoue, Toru Nakano
During the development of mammalian embryonic germ cells, global demethylation and de novo DNA methylation take place. In mouse embryonic germ cells, two PIWI family proteins, MILI and MIWI2, are essential for the de novo DNA methylation of retrotransposons, presumably through PIWI-interacting RNAs (piRNAs). Although piRNA-associated MIWI2 has been reported to play critical roles in the process, its molecular mechanisms have remained unclear. To identify the mechanism, transgenic mice were produced; they contained a fusion protein of MIWI2 and a zinc finger (ZF) that recognized the promoter region of a type A LINE-1 gene...
September 13, 2016: Cell Reports
Jennifer A Erwin, Apuã C M Paquola, Tatjana Singer, Iryna Gallina, Mark Novotny, Carolina Quayle, Tracy A Bedrosian, Francisco I A Alves, Cheyenne R Butcher, Joseph R Herdy, Anindita Sarkar, Roger S Lasken, Alysson R Muotri, Fred H Gage
The healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associated variants (SLAVs) are composed of two classes: L1 retrotransposition insertions and retrotransposition-independent L1-associated variants. We demonstrate that a subset of SLAVs comprises somatic deletions generated by L1 endonuclease cutting activity...
September 12, 2016: Nature Neuroscience
Weilong Guo, Michael Q Zhang, Hong Wu
Although non-CG methylations are abundant in several mammalian cell types, their biological significance is sparsely characterized. We gathered 51 human and mouse DNA methylomes from brain neurons, embryonic stem cells and induced pluripotent stem cells, primordial germ cells and oocytes. We utilized an unbiased sub-motif prediction method and reported CW as the representative non-CG methylation context, which is distinct from CC methylation in terms of sequence context and genomic distribution. A two-dimensional comparison of non-CG methylations across cell types and species was performed...
2016: Scientific Reports
Joyce F Liu, Sangeetha Palakurthi, Qing Zeng, Shan Zhou, Elena Ivanova, Wei Huang, Ioannis K Zervantonakis, Laura M Selfors, Yiping Shen, Colin C Pritchard, Mei Zheng, Vilmos Adleff, Eniko Papp, Huiying Piao, Marian Novak, Susan Fotheringham, Gerburg Wulf, Jessie English, Paul T Kirschmeier, Victor E Velculescu, Cloud P Paweletz, Gordon B Mills, David M Livingston, Joan S Brugge, Ursula A Matulonis, Ronny Drapkin
PURPOSE: Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with high rates of recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate and reproducible target discovery and validation are needed to support further drug development in this disease. EXPERIMENTAL DESIGN: Clinically-annotated patient-derived xenograft (PDX) models were generated from tumor cells isolated from the ascites or pleural fluid of patients undergoing clinical procedures...
August 29, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ildar V Gainetdinov, Kristina Yu Kapitskaya, Elena Yu Rykova, Anastasia A Ponomaryova, Nadezda V Cherdyntseva, Valentin V Vlassov, Pavel P Laktionov, Tatyana L Azhikina
Circulating DNA has recently gained attention as a fast and non-invasive way to assess tumor biomarkers. Since hypomethylation of LINE-1 repetitive elements was described as one of the key hallmarks of tumorigenesis, we aimed to establish whether the methylation level of LINE-1 retrotransposons changes in cell-surface-bound fraction of circulating DNA (csbDNA) of lung cancer patients. Methylated CpG Island Recovery Assay (MIRA) coupled to qPCR-based quantitation was performed to assess integral methylation level of LINE-1 promoters in csbDNA of non-small cell lung cancer patients (n=56) and healthy controls (n=44)...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
B Smolkova, S Miklikova, V Horvathova Kajabova, A Babelova, N El Yamani, M Zduriencikova, I Fridrichova, I Zmetakova, T Krivulcik, L Kalinkova, M Matuskova, L Kucerova, M Dusinska
Epithelial-to-mesenchymal transition (EMT) significantly affects the risk of metastasising in breast cancer. Plasticity and reversibility of EMT suggest that epigenetic mechanisms could be the key drivers of these processes, but little is known about the dynamics of EMT-related epigenetic alterations. We hypothesised that EMT, mediated by autocrine and paracrine signals, will be accompanied by changes in DNA methylation profiles. Therefore, conditioned medium from adipose tissue-derived mesenchymal stromal cells was used for induction of EMT in human breast cancer SK-BR-3 cell line...
August 27, 2016: Neoplasma
Hiroyuki Yamaba, Manami Haba, Mayumi Kunita, Tsutomu Sakaida, Hiroshi Tanaka, Youichi Yashiro, Satoru Nakata
Human dermal fibroblasts (HDFs) are typically flattened or extensible shaped and play a critical role in the metabolism of extracellular matrix components. As the properties of fibroblasts in the dermis are considered to be influenced by their morphology, we investigated the morphological changes induced in fibroblasts by ultraviolet (UV) irradiation as well as the relationship between these changes and collagen metabolism. In this study, we showed that UVA exposure induced morphological changes and reduced collagen contents in HDFs...
August 2016: Experimental Dermatology
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