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Pathology methylation

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https://www.readbyqxmd.com/read/28719605/extracellular-phosphorylation-of-a-receptor-tyrosine-kinase-controls-synaptic-localization-of-nmda-receptors-and-regulates-pathological-pain
#1
Kenji Hanamura, Halley R Washburn, Sean I Sheffler-Collins, Nan L Xia, Nathan Henderson, Dipti V Tillu, Shayne Hassler, Daniel S Spellman, Guoan Zhang, Thomas A Neubert, Theodore J Price, Matthew B Dalva
Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28715960/histone-methylation-by-set-domain-proteins-in-fungi
#2
Michael Freitag
Histone-modifying enzymes are responsible for regulating transcription, recombination, DNA repair, DNA replication, chromatid cohesion, and chromosome segregation. Fungi are ideally suited for comparative chromatin biology because sequencing of numerous genomes from many clades is coupled to existing rich methodology that allows truly holistic approaches, integrating evolutionary biology with mechanistic molecular biology and ecology, promising applications in medicine or plant pathology. While genome information is rich, mechanistic studies on histone modifications are largely restricted to two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and one filamentous fungus, Neurospora crassa-three species that arguably are not representative of this diverse kingdom...
July 17, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28714863/dna-methylation-based-immune-response-signature-improves-patient-diagnosis-in-multiple-cancers
#3
Jana Jeschke, Martin Bizet, Christine Desmedt, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Alexander Koch, Denis Larsimont, Roberto Salgado, Gert Van den Eynden, Karen Willard Gallo, Gianluca Bontempi, Matthieu Defrance, Christos Sotiriou, François Fuks
BACKGROUND: The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS: MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713383/the-toxicological-mechanisms-of-environmental-soot-black-carbon-and-carbon-black-focus-on-oxidative-stress-and-inflammatory-pathways
#4
REVIEW
Rituraj Niranjan, Ashwani Kumar Thakur
The environmental soot and carbon blacks (CBs) cause many diseases in humans, but their underlying mechanisms of toxicity are still poorly understood. Both are formed after the incomplete combustion of hydrocarbons but differ in their constituents and percent carbon contents. For the first time, "Sir Percival Pott" described soot as a carcinogen, which was subsequently confirmed by many others. The existing data suggest three main types of diseases due to soot and CB exposures: cancer, respiratory diseases, and cardiovascular dysfunctions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28712640/resident-calmodulin-primes-nmda-receptors-for-ca-2-dependent-inactivation
#5
Gary J Iacobucci, Gabriela K Popescu
N-methyl-d-aspartate (NMDA) receptors are glutamate- and glycine-gated channels that flux Na(+) and Ca(2+) into postsynaptic neurons during synaptic transmission. The resulting intracellular Ca(2+) transient is essential to physiological and pathological processes related to synaptic development, plasticity, and apoptosis. It also engages calmodulin (CaM) to reduce subsequent NMDA receptor activity in a process known as Ca(2+)-dependent inactivation (CDI). Here, we used whole-cell electrophysiology to measure CDI and computational modeling to dissect the sequence of events that underlies it...
July 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28710355/high-resolution-imaging-of-dna-methylation-dynamics-using-a-zebrafish-reporter
#6
Ranran Zhang, Lian Liu, Yuxiao Yao, Fei Fei, Feng Wang, Qian Yang, Yonghao Gui, Xu Wang
As one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709638/dna-methylation-protects-against-cisplatin-induced-kidney-injury-by-regulating-specific-genes-including-interferon-regulatory-factor-8
#7
Chunyuan Guo, Lirong Pei, Xiao Xiao, Qingqing Wei, Jian-Kang Chen, Han-Fei Ding, Shuang Huang, Guoping Fan, Huidong Shi, Zheng Dong
DNA methylation is an epigenetic mechanism that regulates gene transcription without changing primary nucleotide sequences. In mammals, DNA methylation involves the covalent addition of a methyl group to the 5-carbon position of cytosine by DNA methyltransferases (DNMTs). The change of DNA methylation and its pathological role in acute kidney injury (AKI) remain largely unknown. Here, we analyzed genome-wide DNA methylation during cisplatin-induced AKI by reduced representation bisulfite sequencing. This technique identified 215 differentially methylated regions between the kidneys of control and cisplatin-treated animals...
July 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28706445/histone-demethylase-kdm2b-upregulates-histone-methyltransferase-ezh2-expression-and-contributes-to-the-progression-of-ovarian-cancer-in-vitro-and-in-vivo
#8
Yan Kuang, Fangfang Lu, Jianfeng Guo, Hong Xu, Qi Wang, Chaohuan Xu, Longjia Zeng, Suyi Yi
Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28705657/role-of-glutathione-in-the-regulation-of-epigenetic-mechanisms-in-disease
#9
REVIEW
José Luis García-Giménez, Carlos Romá-Mateo, Gisselle Pérez-Machado, Lorena Peiró-Chova, Federico V Pallardó
Epigenetics is a rapidly growing field that studies gene expression modifications not involving changes in the DNA sequence. Histone H3, one of the basic proteins in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH), a physiological antioxidant and second messenger in cells, a new post-translational modifier of the histone code that alters the structure of the nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes beyond a mere structural function...
July 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28704208/hgnet-bcor-tumors-of-the-cerebellum-clinicopathologic-and-molecular-characterization-of-3-cases
#10
Romain Appay, Nicolas Macagno, Laetitia Padovani, Andrey Korshunov, Marcel Kool, Nicolas André, Didier Scavarda, Torsten Pietsch, Dominique Figarella-Branger
The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors...
July 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28698146/epigenetic-regulation-of-epithelial-mesenchymal-transition-by-kdm6a-histone-demethylase-in-lung-cancer-cells
#11
Minoru Terashima, Akihiko Ishimura, Sasithorn Wanna-Udom, Takeshi Suzuki
Histone methylation is associated with various biological and pathological processes including cancer development. KDM6A is a candidate tumor suppressor gene that encodes a histone H3 lysine 27 (H3K27) demethylase. In this study, we discovered that ectopic expression of KDM6A antagonized TGF-β-induced epithelial-mesenchymal transition (EMT) and cell migration of lung cancer cell lines through its demethylase activity. KDM6A counteracted TGF-β-dependent changes in the expression of EMT-related genes such as CDH1/E-cadherin, FN1/Fibronectin, ZEB family and microRNA-200 family...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#12
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
July 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28688796/fatty-acid-based-lipidomics-and-membrane-remodeling-induced-by-apoe3-and-apoe4-in-human-neuroblastoma-cells
#13
Paraskevi Prasinou, Ioannis Dafnis, Giorgia Giacometti, Carla Ferreri, Angeliki Chroni, Chryssostomos Chatgilialoglu
Apolipoprotein E (apoE) is a major lipid carrier of the lipoprotein transport system that plays critical roles in various pathologies. Human apoE has three common isoforms, the apoE4 being associated with Alzheimer's disease. This is the first study in the literature investigating the effects of apoE (apoE3 and apoE4 isoforms) on membrane fatty acid profile in neuroblastoma SK-N-SH cells. Fatty acid analyses were carried out by gas chromatography of the corresponding methyl esters (FAME). We observed the occurrence of membrane fatty acid remodeling in the presence of each of the two apoE isoforms...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28684555/statistically-robust-methylation-calling-for-whole-transcriptome-bisulfite-sequencing-reveals-distinct-methylation-patterns-for-mouse-rnas
#14
Carine Legrand, Francesca Tuorto, Mark Hartmann, Reinhard Liebers, Dominik Jacob, Mark Helm, Frank Lyko
(Cytosine-5) RNA methylation plays an important role in several biologically and pathologically relevant processes. However, owing to methodological limitations, the transcriptome-wide distribution of this mark has remained largely unknown. We previously established RNA bisulfite sequencing as a method for the analysis of RNA (cytosine-5) methylation patterns at single-base resolution. More recently, next-generation sequencing has provided opportunities to establish transcriptome-wide maps of this modification...
July 6, 2017: Genome Research
https://www.readbyqxmd.com/read/28682231/g%C3%A3-n%C3%A3-tique-et-%C3%A3-pig%C3%A3-n%C3%A3-tique-des-troubles-des-conduites-alimentaires
#15
Nicolas Ramoz, Julia Clarke, Philip Gorwood
Eating disorders (EDs) are complex and multifactorial psychiatric illnesses that induce significant and sustained pathological disruption of food intake. The Diagnostic and Statistical Manual of Mental Illnesses (DSM-5) describes the clinical criteria of major disorders including anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). The neurobiological basis of food intake is well characterized. Epidemiological studies reported a heritability about 70% in AN and 60% in BN, suggesting that genetic factors are involved in the vulnerability to EDs...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28676344/crispr-epigenome-editing-of-akap150-in-drg-neurons-abolishes-degenerative-ivd-induced-neuronal-activation
#16
Joshua D Stover, Niloofar Farhang, Kristofer C Berrett, Jason Gertz, Brandon Lawrence, Robby D Bowles
Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28673833/the-glutamate-receptor-antagonists-cnqx-and-mpep-decrease-fast-ripple-events-in-rats-treated-with-kainic-acid
#17
Laura Medina-Ceja, Carla García-Barba
Fast ripples (FR) are high frequency oscillations (250-600Hz) that have been associated with epilepsy. FR are assumed to be generated in small areas of the hippocampus (1mm(3)) that contain pathologically interconnected glutamate pyramidal cell clusters. Additionally, a relation between glutamate neurotransmission and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainite (AMPA/KA) and metabotropic mGluR5 receptors is well established. Therefore, we hypothesized that antagonism of these glutamate receptors would decrease FR activity...
June 30, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28672915/induction-of-reprogramming-of-human-amniotic-epithelial-cells-into-ips-cells-by-overexpression-of-yap-oct4-and-sox2-through-the-activation-of-the-hippo-yap-pathway
#18
Yanhui Zhao, Xinfeng Fei, Jianming Guo, Gang Zou, Weidong Pan, Jingju Zhang, Yongyi Huang, Te Liu, Weiwei Cheng
The present study has reported a novel method for producing induced pluripotent stem (iPS) cells. Primary human amniotic epithelial cells (HuAECs) were isolated from the amniotic membranes of pregnant women who received Cesarean sections. These cells were infected with retroviruses carrying octamer-binding transcription factor 4 (Oct4), (sex determining region Y)-box 2 (Sox2) and Yes-associated protein (Yap) (OSY). Following in vitro culture for ~14 days, epithelial-like HuAECs exhibited several iPS clone-like cell colonies (OSY-iPS)...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28671923/lncrnas-dna-methylation-and-the-pathobiology-of-exfoliation-glaucoma
#19
William M Johnson, Laura K Finnegan, Michael A Hauser, W Daniel Stamer
Exfoliation glaucoma (XFG) is a clinically aggressive and genetically distinct form of glaucoma that results in neuronal death and irreversible blindness. Gene variants associate with many neurodegenerative diseases including XFG, Parkinson's disease (PD) and Alzheimer's disease (AD). Intriguingly, variants found within the same gene can either confer risk for or provide protection against all 3 of these diseases, complicating the genetic component of pathology. Unfortunately, studies that examine proteins encoded by genes having relevant variants have failed to produce therapeutic interventions that slow or stop the progression of XFG, PD, or AD in patients...
June 30, 2017: Journal of Glaucoma
https://www.readbyqxmd.com/read/28670441/znf300-tight-self-regulation-and-functioning-through-dna-methylation-and-histone-acetylation
#20
Feng-Juan Yan, Jingyi Fan, Zan Huang, Jun-Jian Zhang
BACKGROUND: Accumulating evidence demonstrates that the KRAB-ZNFs involve in various biological processes. As a typical member of KRAB-ZNFs, dysregulation of ZNF300 contributes to multiple pathologies such as leukemia and cancer. However, mechanisms underlying ZNF300 tight regulation and its pathophysiological function remain largely unknown. METHODS: The effect of ZNF300ZFR on gene transcriptional activity was measured by Dual luciferase reporter system. ChIP-PCR assay were performed to detect the enrichment of ZNF300 protein and H3K9Ac in the ZNF300 gene...
2017: Cell & Bioscience
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