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https://www.readbyqxmd.com/read/27912315/genetics-of-infectious-and-inflammatory-diseases-overlapping-discoveries-from-association-and-exome-sequencing-studies
#1
David Langlais, Nassima Fodil, Philippe Gros
Genome technologies have defined a complex genetic architecture in major infectious, inflammatory, and autoimmune disorders. High density marker arrays and Immunochips have powered genome-wide association studies (GWAS) that have mapped nearly 450 genetic risk loci in 22 major inflammatory diseases, including a core of common genes that play a central role in pathological inflammation. Whole-exome and whole-genome sequencing have identified more than 265 genes in which mutations cause primary immunodeficiencies and rare forms of severe inflammatory bowel disease...
December 1, 2016: Annual Review of Immunology
https://www.readbyqxmd.com/read/27910903/prostate-cancer-patients-negative-biopsy-controls-discrimination-by-untargeted-metabolomics-analysis-of-urine-by-lc-qtof-upstream-information-on-other-omics
#2
M A Fernández-Peralbo, E Gómez-Gómez, M Calderón-Santiago, J Carrasco-Valiente, J Ruiz-García, M J Requena-Tapia, M D Luque de Castro, F Priego-Capote
The existing clinical biomarkers for prostate cancer (PCa) diagnosis are far from ideal (e.g., the prostate specific antigen (PSA) serum level suffers from lack of specificity, providing frequent false positives leading to over-diagnosis). A key step in the search for minimum invasive tests to complement or replace PSA should be supported on the changes experienced by the biochemical pathways in PCa patients as compared to negative biopsy control individuals. In this research a comprehensive global analysis by LC-QTOF was applied to urine from 62 patients with a clinically significant PCa and 42 healthy individuals, both groups confirmed by biopsy...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#3
Tushar D Bhagat, Yiyu Zou, Shizeng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Wejuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, Maria C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27906710/who-s-your-daddy-paternal-inheritance-of-metabolic-disease-risk
#4
Elvira Isganaitis, Harumi Suehiro, Connie Cardona
PURPOSE OF REVIEW: Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. RECENT FINDINGS: The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation...
November 30, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27906075/nuclear-bodies-reorganize-during-myogenesis-in-vitro-and-are-differentially-disrupted-by-expression-of-fshd-associated-dux4
#5
Sachiko Homma, Mary Lou Beermann, Bryant Yu, Frederick M Boyce, Jeffrey Boone Miller
BACKGROUND: Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD)...
December 1, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#6
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27903964/lncrna-h19-inhibits-autophagy-by-epigenetically-silencing-of-diras3-in-diabetic-cardiomyopathy
#7
Chuanjun Zhuo, Ronghuan Jiang, Xiaodong Lin, Mingjing Shao
We previously generated a rat model of diabetic cardiomyopathy and found that the expression of long non-coding RNA H19 was downregulated. The present study was aimed to explore the pathogenic role of H19 in the development of diabetic cardiomyopathy. Overexpression of H19 in diabetic rats attenuated cardiomyocyte autophagy and improved left ventricular function. High glucose was found to reduce H19 expression and increase autophagy in cultured neonatal cardiomyocytes. The results of RNA-binding protein immunoprecipitation showed that H19 could directly bind with EZH2 in cardiomyocytes...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903230/glucocorticoid-receptor-interacting-co-regulators-putative-candidates-for-future-drug-targeting-therapy
#8
Alessia Di Silvestre, Marianna Lucafò, Sara De Iudicibus, Alessandro Ventura, Stefano Martelossi, Gabriele Stocco, Giuliana Decorti
Glucocorticoids (GCs) are largely used in different inflammatory, autoimmune and proliferative diseases. To date their mechanism of action is not completely clear and more studies are necessary, in particular to explain the great interindividual variability in clinical response. In this panorama the glucocorticoid receptor (GR) has an important role: in fact it regulates the pharmacological response thanks to the capability to interact with different molecules (DNA, RNA, ncRNA and proteins) that are known to influence its activity...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27899719/a-novel-hypothesis-for-histone-to-protamine-transition-in-bos-taurus-spermatozoa
#9
Gerly Sillaste, Lauris Kaplinski, Riho Meier, Ülle Jaakma, Elo Eriste, Andres Salumets
DNA compaction with protamines in sperm is essential for successful fertilization. However, a portion of sperm chromatin remains less tightly packed with histones, which genomic location and function remain unclear. We extracted and sequenced histone-associated DNA from sperm of nine ejaculates from three bulls. We found that the fraction of retained histones varied between samples but the variance was similar between samples from the same and different individuals. The most conserved regions showed similar abundance across all samples, while in other regions their presence correlated with the size of histone fraction...
November 29, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27899259/overexpression-of-the-long-non-coding-rna-spry4-it1-promotes-tumor-cell-proliferation-and-invasion-by-activating-ezh2-in-hepatocellular-carcinoma
#10
Meng Zhou, Xiao-Yu Zhang, Xi Yu
BACKGROUND: Increasing evidences have demonstrated that the dysregulation of long non-coding RNAs (lncRNAs) may act as an important role in tumor progression. The long non-coding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) has been reported in some cancer including regulating cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown. METHODS: The lncRNA SPRY4-IT1 was detected by quantitative real time PCR (qRT-PCR) in HCC cell lines, CCK8 cell proliferation and transwell invasion assays were performed to detect the GC cell proliferation and invasion abilities...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27896724/genomic-database-searching
#11
James R A Hutchins
The availability of reference genome sequences for virtually all species under active research has revolutionized biology. Analyses of genomic variations in many organisms have provided insights into phenotypic traits, evolution and disease, and are transforming medicine. All genomic data from publicly funded projects are freely available in Internet-based databases, for download or searching via genome browsers such as Ensembl, Vega, NCBI's Map Viewer, and the UCSC Genome Browser. These online tools generate interactive graphical outputs of relevant chromosomal regions, showing genes, transcripts, and other genomic landmarks, and epigenetic features mapped by projects such as ENCODE...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27895308/epigenetic-inhibition-of-mir-663b-by-long-non-coding-rna-hotair-promotes-pancreatic-cancer-cell-proliferation-via-up-regulation-of-insulin-like-growth-factor-2
#12
Huihua Cai, Yong An, Xuemin Chen, Donglin Sun, Tongbing Chen, Yan Peng, Feng Zhu, Yong Jiang, Xiaozhou He
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Although microRNAs are involving in the carcinogenesis and development of pancreatic cancer, little information is known regarding the role of miR-663b in pancreatic cancer. In this study, the expression of miR-663b in pancreatic cancer cells was down-regulated by hypermethylation in its putative promoter region, and overexpression of miR-663b repressed cell proliferation, invasion and migration, and induced apoptosis in pancreatic cancer cells...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895219/primer-in-genetics-and-genomics-article-1-dna-genes-and-chromosomes
#13
Janice S Dorman, Mandy J Schmella, Susan W Wesmiller
Precision medicine refers to the practice of determining a patient's unique genetic, biomarker, and other characteristics for the purpose of improving his or her clinical outcomes. Not all patients with the same clinical diagnosis respond equally to identical treatment regimens. By examining patients at the molecular level, health-care providers will be better able to apply the most effective therapies that each individual requires. To understand precision medicine, nurses must have a solid understanding of genomics and proteomics...
November 28, 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27893417/genetic-and-epigenetic-silencing-of-mircorna-506-3p-enhances-cotl1-oncogene-expression-to-foster-non-small-lung-cancer-progression
#14
Shanqi Guo, Peiying Yang, Xingkang Jiang, Xiaojiang Li, Yuanyuan Wang, Xin Zhang, Binxu Sun, Yao Zhang, Yingjie Jia
Although previous studies suggested that microRNA-506-3p (miR-506-3p) was frequently downregulated, and functioned as a tumor suppressor in several cancers, the biological role and intrinsic regulatory mechanisms of miR-506-3p in non-small cell lung cancer (NSCLC) remain elusive. The present study found miR-506-3p expression was downregulated in advanced NSCLC tissues and cell lines. The expression of miR-506-3p in NSCLC was inversely correlated with larger tumor size, advanced TNM stage and lymph node metastasis...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892767/epigenetic-modifications-in-multiple-myeloma-recent-advances-on-the-role-of-dna-and-histone-methylation
#15
Nicola Amodio, Patrizia D'Aquila, Giuseppe Passarino, Pierfrancesco Tassone, Dina Bellizzi
Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway...
November 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27882772/mirnas-differentially-expressed-by-next-generation-sequencing-in-cord-blood-buffy-coat-samples-of-boys-and-girls
#16
Daneida Lizarraga, Karen Huen, Mary Combs, Maria Escudero-Fung, Brenda Eskenazi, Nina Holland
AIM: Differences in children's development and susceptibility to diseases and exposures have been observed by sex, yet human studies of sex differences in miRNAs are limited. MATERIALS & METHODS: The genome-wide miRNA expression was characterized by sequencing-based EdgeSeq assay in cord blood buffy coats from 89 newborns, and 564 miRNAs were further analyzed. RESULTS: Differential expression of most miRNAs was higher in boys. Neurodevelopment, RNA metabolism and metabolic ontology terms were enriched among miRNA targets...
November 24, 2016: Epigenomics
https://www.readbyqxmd.com/read/27880937/prognostic-relevance-of-mirna-155-methylation-in-anaplastic-glioma
#17
Maximilian Georg Schliesser, Rainer Claus, Thomas Hielscher, Christiane Grimm, Dieter Weichenhan, Jonas Blaes, Benedikt Wiestler, Peter Hau, Johannes Schramm, Felix Sahm, Elisa K Weiß, Markus Weiler, Constance Baer, Friederike Schmidt-Graf, Gabriele Schackert, Manfred Westphal, Anne Hertenstein, Patrick Roth, Norbert Galldiks, Christian Hartmann, Torsten Pietsch, Joerg Felsberg, Guido Reifenberger, Michael Christoph Sabel, Frank Winkler, Andreas von Deimling, Christoph Meisner, Peter Vajkoczy, Michael Platten, Michael Weller, Christoph Plass, Wolfgang Wick
The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies.To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879268/transcriptional-selectivity-of-epigenetic-therapy-in-cancer
#18
Takahiro Sato, Matteo Cesaroni, Woonbok Chung, Shoghag Panjarian, Anthony Tran, Jozef Madzo, Yasuyuki Okamoto, Hanghang Zhang, Xiaowei Chen, Jaroslav Jelinek, Jean-Pierre J Issa
A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation and ChIP-seq analyses the epigenetic response of a set of colon, breast and leukemia cancer cell lines to small molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343)...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27878142/microrna-biogenesis-epigenetic-modifications-as-another-layer-of-complexity-in-the-microrna-expression-regulation
#19
Susheel Sagar Bhat, Artur Jarmolowski, Zofia Szweykowska-Kulińska
Since their discovery, microRNAs have led to a huge shift in our understanding of the regulation of key biological processes. The discovery of epigenetic modifications that affect microRNA expression has added another layer of complexity to the already tightly controlled regulatory machinery. Modifications like uridylation, adenylation and RNA editing have been shown to have variable effects on miRNA biogenesis and action. Methylation of the N6 adenosine has been studied extensively in mRNA. Presence of the N6-methyl-adenosine (m(6)A) mark and its critical importance in miRNA biogenesis in animals adds to our understanding of the regulatory mechanisms, while its effect on miRNA biogenesis in plants is yet to be understood...
November 22, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27876379/microrna-profiling-of-human-intermediate-monocytes
#20
Adam M Zawada, Lu Zhang, Insa E Emrich, Kyrill S Rogacev, Nicolas Krezdorn, Björn Rotter, Danilo Fliser, Yvan Devaux, Loems Ziegler-Heitbrock, Gunnar H Heine
Among the three human monocyte subsets, intermediate CD14++CD16+ monocytes have been characterized as particularly proinflammatory cells in experimental studies and as potential biomarkers of cardiovascular risk in clinical cohorts. To further substantiate the distinct role of intermediate monocytes within human monocyte heterogeneity, we assessed subset-specific expression of miRNAs as central epigenetic regulators of gene expression. We hypothesized that intermediate monocytes have a distinct miRNA profile compared to classical and non-classical monocytes...
November 13, 2016: Immunobiology
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