Detecting Methylation Signatures in Neurodegenerative Disease by Density‑Based Clustering of Applications with Reducing Noise Saurav Mallik1 & Zhongming Zhao1,2,3*
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Epigenetics of the Synapse in Neurodegeneration
Current Neurology and Neuroscience Reports (2019) 19:72 https://doi.org/10.1007/s11910-019-0995-y GENETICS (V. BONIFATI, SECTION EDITOR) Epigenetics of the Synapse in Neurodegeneration Mary Xylaki1 & Benedict Atzler1 & Tiago Fleming Outeiro1,2,3 # The Author(s) 2019 Abstract Purpose of Review In the quest for understanding the pathophysiological processes underlying degeneration of nervous systems, synapses are emerging as sites of great interest as synaptic dysfunction is thought to play a role in the initiation and progression of neuronal loss. In particular, the synapse is an interesting target for the effects of epigenetic mechanisms in neurodegeneration. Here, we review the recent advances on epigenetic mechanisms driving synaptic compromise in major neurodegenerative disorders. Recent Findings Major developments in sequencing technologies enabled the mapping of transcriptomic patterns in human postmortem brain tissues in various neurodegenerative diseases, and also in cell and animal models. These studies helped identify changes in classical neurodegeneration pathways and discover novel targets related to synaptic degeneration. Summary Identifying epigenetic patterns indicative of synaptic defects prior to neuronal degeneration may provide the basis for future breakthroughs in the field of neurodegeneration. Keywords Synapse . Neurodegenerative diseases . DNA methylation . Histone modifications . Noncoding RNAs . Neuroepigenetics Abbreviations CpG Cytosine-phosphate-guanine 3xTg-AD Triple-transgenic AD CpH Non-CpG 5xFAD Five familial -
Neuroepigenetics: Introduction to the Special Issue on Epigenetics in Neurodevelopment and Neurological Diseases
Experimental Neurology 268 (2015) 1–2 Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr Editorial Neuroepigenetics: Introduction to the special issue on epigenetics in neurodevelopment and neurological diseases Gene expression profile represents the molecular state of a cell at a The structural unit of the chromatin is nucleosome, which is com- given time and is dynamically regulated and precisely controlled in re- prised of DNA chains wrapping around histone proteins. Nucleosomes sponse to external stimuli. While the DNA sequences are the ultimate can be either loosely or densely packed, which is associated with active templates for gene transcription, epigenetic features of the genome, in- or suppressed gene transcription, respectively. The chemical modifica- cluding modifications of histones, methylation of cytosine nucleotides tions of the histone tail, most commonly acetylation, methylation and of the genomic DNA, 3-dimensional interaction of genomic regions, phosphorylation, are one of the determinants of the structural status and the expression of various forms of non-coding RNAs, regulate the of the chromatin. Histone acetylation is in general correlates with accessibility and processability of the genomic loci and add another loose chromatin and active gene expression. On the other hand, layer of regulation of gene expression beyond the heritable DNA se- Histone-3 lysine-4 trimethylation (H3K4Me3) plays both positive and quences. For decades, some epigenetic properties of the genome, such negative roles in regulating gene expression, depending on the combi- as DNA methylation, have been considered as stable and inheritable nation of other histone modifications. The article by Shen and col- marks. -
CAMB713: Neuroepigenetics
CAMB713: Neuroepigenetics TIME: Thursdays 1-3pm 8/29 – 12/12 (organizational meeting 8/29, no class on 9/5 and 11/28) LOCATION: BRB 1413 COURSE DIRECTORS: Zhaolan (Joe) Zhou 215.746.5025 [email protected] Elizabeth Heller 215.573.7038 [email protected] Hao Wu 215.573.9360 [email protected] GOALS: This is a course intended to bring students up to date concerning our understanding of Neural Epigenetics. It is based on assigned topics and readings covering a variety of experimental systems and concepts in the field of Neuroepigenetics, formal presentations by individual students, critical evaluation of primary data, and in-depth discussion of potential issues and future directions, with goals to: 1) Review basic concepts of epigenetics in the context of neuroscience 2) Learn to critically evaluate a topic (not a single paper) and rigor of prior research 3) Improve experimental design and enhance rigor and reproducibility 4) Catch up with the most recent development in neuroepigenetics 5) Develop professional presentation skills - be a story teller FORMAT: Each week will focus on a specific topic of Neuroepigenetics via a “seminar” style presentation by a class member with the following expectations: Consultation with preceptor prior to presentation Introduction (~20 min): Context of topic in the field Historic perspectives of the topic Current understandings Primary data (~40 min): Questions of interest Design of experiments Interpretation of data Discussion (~20 min): Issues/challenges Proposed future -
Bayesian GWAS and Network Analysis Revealed New Candidate Genes for Number of Teats in Pigs
J Appl Genetics DOI 10.1007/s13353-014-0240-y ANIMAL GENETICS • ORIGINAL PAPER Bayesian GWAS and network analysis revealed new candidate genes for number of teats in pigs L. L. Verardo & F. F. Silva & L. Varona & M. D. V. Resende & J. W. M. Bastiaansen & P. S. Lopes & S. E. F. Guimarães Received: 7 March 2014 /Revised: 27 May 2014 /Accepted: 23 July 2014 # Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2014 Abstract The genetic improvement of reproductive traits comparisons based on deviance posterior distribution indicat- such as the number of teats is essential to the success of the ed the superiority of Gaussian model. In general, our results pig industry. As opposite to most SNP association studies that suggest the presence of 19 significant SNPs, which mapped consider continuous phenotypes under Gaussian assumptions, 13 genes. Besides, we predicted gene interactions through this trait is characterized as a discrete variable, which could networks that are consistent with the mammals known breast potentially follow other distributions, such as the Poisson. biology (e.g., development of prolactin receptor signaling, and Therefore, in order to access the complexity of a counting cell proliferation), captured known regulation binding sites, random regression considering all SNPs simultaneously as and provided candidate genes for that trait (e.g., TINAGL1 covariate under a GWAS modeling, the Bayesian inference and ICK). tools become necessary. Currently, another point that deserves to be highlighted in GWAS is the genetic dissection of com- Keywords Counting data . Genes . Reproductive traits . SNP plex phenotypes through candidate genes network derived association from significant SNPs. -
Human Lectins, Their Carbohydrate Affinities and Where to Find Them
biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body. -
Contribution of Neuroepigenetics to Huntington's Disease
Francelle L, Lotz C, Outeiro T, Brouillet E, Merienne K. Contribution of Neuroepigenetics to Huntington’s Disease. Frontiers in Human Neuroscience 2017, 11, 17. Copyright: © 2017 Francelle, Lotz, Outeiro, Brouillet and Merienne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. DOI link to article: https://doi.org/10.3389/fnhum.2017.00017 Date deposited: 19/12/2017 This work is licensed under a Creative Commons Attribution 4.0 International License Newcastle University ePrints - eprint.ncl.ac.uk fnhum-11-00017 January 25, 2017 Time: 15:35 # 1 REVIEW published: 30 January 2017 doi: 10.3389/fnhum.2017.00017 Contribution of Neuroepigenetics to Huntington’s Disease Laetitia Francelle1*, Caroline Lotz2, Tiago Outeiro1, Emmanuel Brouillet3 and Karine Merienne2 1 Department of NeuroDegeneration and Restorative Research, University Medical Center Goettingen, Goettingen, Germany, 2 CNRS UMR 7364, Laboratory of Cognitive and Adaptive Neurosciences, University of Strasbourg, Strasbourg, France, 3 Commissariat à l’Energie Atomique et aux Energies Alternatives, Département de Recherche Fondamentale, Institut d’Imagerie Biomédicale, Molecular Imaging Center, Neurodegenerative diseases Laboratory, UMR 9199, CNRS Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington’s disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. -
Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications
Stem Cell Rev and Rep DOI 10.1007/s12015-016-9662-8 Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications Behnam Ahmadian Baghbaderani 1 & Adhikarla Syama2 & Renuka Sivapatham3 & Ying Pei4 & Odity Mukherjee2 & Thomas Fellner1 & Xianmin Zeng3,4 & Mahendra S. Rao5,6 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract We have recently described manufacturing of hu- help determine which set of tests will be most useful in mon- man induced pluripotent stem cells (iPSC) master cell banks itoring the cells and establishing criteria for discarding a line. (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Keywords Induced pluripotent stem cells . Embryonic stem Reports, 5(4), 647–659, 2015). In this manuscript, we de- cells . Manufacturing . cGMP . Consent . Markers scribe the detailed characterization of the two iPSC clones generated using this process, including whole genome se- quencing (WGS), microarray, and comparative genomic hy- Introduction bridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibra- Induced pluripotent stem cells (iPSCs) are akin to embryonic tion material and with a reporter subclone and lines made by a stem cells (ESC) [2] in their developmental potential, but dif- similar process from different donors. We believe that iPSCs fer from ESC in the starting cell used and the requirement of a are likely to be used to make multiple clinical products. We set of proteins to induce pluripotency [3]. Although function- further believe that the lines used as input material will be used ally identical, iPSCs may differ from ESC in subtle ways, at different sites and, given their immortal status, will be used including in their epigenetic profile, exposure to the environ- for many years or even decades. -
About Microneurotrophins
About MicroNeurotrophins UNLOCKING THE PROMISE OF NEUROTROPHINS Most researchers now agree that ALS and other neurodegenerative diseases including Multiple Sclerosis, Parkinson’s and Alzheimer’s are remarkably complex, almost certainly involving a combination of different biological, genetic and external triggers. Yet, time and again, drug development for these multi-faceted diseases has focused almost exclusively on medications that only target one factor likely causing the disease. It’s not surprising that these single-target drugs have uniformly failed in previous clinical trials. With this in mind, esteemed pharmacologist Dr. Achilleas Gravanis and his team of scientists from Bionature, a spin-off of the University of Crete in Greece, began searching for a way to effectively address the multiple triggers contributing to the onset and progression of neurodegenerative diseases. Their investigation led them to study neurotrophins, proteins naturally secreted in the brain that transmit signals between motor neurons by binding to and activating two different types of receptors, TrkA and p75, found on the surface of nerve cells. Twenty years of research have shown that neurotrophins help motor neurons develop, grow, function, signal and even repair themselves. Neurotrophins also appear to protect motor neurons from stress and death. By contrast, ALS causes motor neurons to degenerate and die and ALS patients experience a profound loss of neurotrophins as the disease progresses. However, numerous clinical trials have been unable to prove the efficacy of neurotrophins to treat ALS and other neurodegenerative diseases. TWO STARTLING DISCOVERIES To understand why, Dr. Gravanis and his colleagues carefully examined past studies on neurotrophins, and two astonishing observations became apparent to them. -
Psychotropic Drug-Induced Genetic- Epigenetic Modulation of CRTC1
Delacrétaz et al. Clinical Epigenetics (2019) 11:198 https://doi.org/10.1186/s13148-019-0792-0 RESEARCH Open Access Psychotropic drug-induced genetic- epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients Aurélie Delacrétaz1, Anaïs Glatard1, Céline Dubath1, Mehdi Gholam-Rezaee2, Jose Vicente Sanchez-Mut3, Johannes Gräff3, Armin von Gunten4, Philippe Conus5 and Chin B. Eap1,6* Abstract Background: Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples. Results: Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p =0.03). -
High Resolution Physical Map of Porcine Chromosome 7 QTL Region and Comparative Mapping of This Region Among Vertebrate Genomes
High resolution physical map of porcine chromosome 7 QTL region and comparative mapping of this region among vertebrate genomes Julie Demars, Juliette Riquet, Katia Feve, Mathieu Gautier, Mireille Morisson, Olivier Demeure, Christine Renard, Patrick Chardon, Denis Milan To cite this version: Julie Demars, Juliette Riquet, Katia Feve, Mathieu Gautier, Mireille Morisson, et al.. High resolution physical map of porcine chromosome 7 QTL region and comparative mapping of this region among vertebrate genomes. BMC Genomics, BioMed Central, 2006, 7, pp.13. 10.1186/1471-2164-7-13. hal-02661326 HAL Id: hal-02661326 https://hal.inrae.fr/hal-02661326 Submitted on 30 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. BMC Genomics BioMed Central Research article Open Access High resolution physical map of porcine chromosome 7 QTL region and comparative mapping of this region among vertebrate genomes Julie Demars1, Juliette Riquet1, Katia Feve1, Mathieu Gautier2, Mireille Morisson1, Olivier Demeure3, Christine Renard4, Patrick Chardon4 and Denis Milan*1 Address: -
The Disruption Ofcelf6, a Gene Identified by Translational Profiling
2732 • The Journal of Neuroscience, February 13, 2013 • 33(7):2732–2753 Neurobiology of Disease The Disruption of Celf6, a Gene Identified by Translational Profiling of Serotonergic Neurons, Results in Autism-Related Behaviors Joseph D. Dougherty,1,2 Susan E. Maloney,1,2 David F. Wozniak,2 Michael A. Rieger,1,2 Lisa Sonnenblick,3,4,5 Giovanni Coppola,4 Nathaniel G. Mahieu,1 Juliet Zhang,6 Jinlu Cai,8 Gary J. Patti,1 Brett S. Abrahams,8 Daniel H. Geschwind,3,4,5 and Nathaniel Heintz6,7 Departments of 1Genetics and 2Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, 3UCLA Center for Autism Research and Treatment, Semel Institute for Neuroscience and Behavior, 4Program in Neurogenetics, Department of Neurology, and 5Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, 6Laboratory of Molecular Biology, Howard Hughes Medical Institute, and 7The GENSAT Project, Rockefeller University, New York, New York 10065, and 8Departments of Genetics and Neuroscience, Albert Einstein College of Medicine, New York, New York 10461 The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. -
CLEC2B Recombinant Protein Description Product Info
ABGENEX Pvt. Ltd., E-5, Infocity, KIIT Post Office, Tel : +91-674-2720712, +91-9437550560 Email : [email protected] Bhubaneswar, Odisha - 751024, INDIA 32-3546: CLEC2B Recombinant Protein Alternative C-type lectin domain family 2 member B,Activation-induced C-type lectin,C-type lectin superfamily member Name : 2,IFN-alpha-2b-inducing-related protein 1,CLEC2B,AICL,CLECSF2,IFNRG1,HP10085. Description Source : Escherichia Coli. CLEC2B Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 147 amino acids (26-149 a.a) and having a molecular mass of 16.9kDa.CLEC2B is fused to a 23 amino acid His-tag at N-terminus & purified by proprietary chromatographic techniques. C-type Lectin Domain Family 2, Member B (CLEC2B) belongs to the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of the CTL/CTLD family share a common protein fold and have various functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The CLEC2B gene is closely connected to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. CLEC2B is expressed preferentially in lymphoid tissues, and in most hematopoietic cell types. Product Info Amount : 20 µg Purification : Greater than 90.0% as determined by SDS-PAGE. CLEC2B protein solution (1mg/ml) containing 20mM Tris-HCl buffer (pH 8.0), 2M UREA and 10% Content : glycerol. Store at 4°C if entire vial will be used within 2-4 weeks. Store, frozen at -20°C for longer periods of Storage condition : time.