Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression Lauren Edwards, Rohit Gupta, and Fabian Volker Filipp
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EPA's Dsstox Database: History of Development of a Curated Chemistry
EPA Public Access Author manuscript Comput Toxicol. Author manuscript; available in PMC 2021 January 07. About author manuscripts | Submit a manuscript Published in final edited form as: EPA Author Manuscript Author EPA Manuscript Author EPA Comput Toxicol Manuscript Author . EPA 2019 November 1; 12: . doi:10.1016/j.comtox.2019.100096. EPA’s DSSTox database: History of development of a curated chemistry resource supporting computational toxicology research Christopher M. Grulkea, Antony J. Williamsa, Inthirany Thillanadarajahb, Ann M. Richarda,* aNational Center for Computational Toxicology, Office of Research & Development, US Environmental Protection Agency, Mail Drop D143-02, Research Triangle Park, NC 27711, USA bSenior Environmental Employment Program, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA Abstract The US Environmental Protection Agency’s (EPA) Distributed Structure-Searchable Toxicity (DSSTox) database, launched publicly in 2004, currently exceeds 875 K substances spanning hundreds of lists of interest to EPA and environmental researchers. From its inception, DSSTox has focused curation efforts on resolving chemical identifier errors and conflicts in the public domain towards the goal of assigning accurate chemical structures to data and lists of importance to the environmental research and regulatory community. Accurate structure-data associations, in turn, are necessary inputs to structure-based predictive models supporting hazard and risk assessments. In 2014, the legacy, manually curated DSSTox_V1 content was migrated to a MySQL data model, with modern cheminformatics tools supporting both manual and automated curation processes to increase efficiencies. This was followed by sequential auto-loads of filtered portions of three public datasets: EPA’s Substance Registry Services (SRS), the National Library of Medicine’s ChemID, and PubChem. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Lorena Novoa-Aponte
A Strain: fl/fl ∆hep Strain: fl/fl ∆hep AnalysisAAV: ofLuc the ironLuc chaperonePCBP1-WT PCBP1PCBP1-∆Fe interactome:PCBP1-∆RNA PCBP1 variant intersection of DNA repair and iron traffickingAAV: Luc Luc WT ∆Fe ∆RNA PCBP1 −40 Lorena Novoa-Aponte a*, Sarju J. Patel a, Olga Protchenko a, James Wohlschlegel b, Caroline C. Philpott a −40 PCBP1, IHC PCBP1, GAPDH - a Genetics and Metabolism Section,a NIDDK, NIH, Bethesda, MD, USA. b Department of Biological Chemistry, UCLA, Los Angeles, CA, USA C.C. Philpott, et al. *[email protected] 80 B P = 0.0262 60 40 1. Iron is essential but toxic 2. Increased DNA damage in cells lacking PCBP1 ns H&E ? + 20 C.C. Philpott, et al. Iron is used as an essential cofactor by several enzymes involved in DNA ⦿ Increased TUNEL in cells and tissue livers from mice lacking PCBP1. ? replication and repair. However, unchaperoned iron promotes redox ⦿ PCBP1 binds both, iron and single-stranded nucleicTG, nmol/mg protein 0 acids. stress that may affect DNA stability. Strain: Δhep Δhep Δhep ? ⦿ The iron binding activity of PCBP1 controls suppressionAAV: of DNA damage C WT ∆Fe ∆RNA PCBP1 variant ? Iron storage HEK293 cells Mouse Liver ? A 8 siNT+P1var 100 ? A 8 var siPCBP1 2 ? Mammals use the iron siNT+P1 ns var Fe-S cluster assembly 6 siPCBP1+P1siPCBP1 80 ADI1 TUNEL chaperone PCBP1 to var ? 6 siPCBP1+P1 metalate several iron- 60 = 0.0468 = 0.0354 = 0.0465 cell / mm population P P P population + dependent enzymes + 4 + 4 ? 40 Degradation of HIF1α Fig. 3. Iron chaperone-mediated handling of cytosolic labile iron pool. -
1 Effects Ethinyl Estradiol Ethinyl Estradiol & Its Effects On
1 Effects Ethinyl Estradiol Ethinyl Estradiol & Its Effects on Cardiovascular Health Mary Eilert Lourdes University Spring 2019 BIO 490 Section A Dr. Anjali Gray 2 Effects Ethinyl Estradiol ABSTRACT Combined hormonal birth control regulates the menstrual cycle in women by manipulating the hormonal level. Combined hormonal contraception utilizes progestin and Ethinyl estradiol, which are synthetics of progesterone and estrogen. These synthetic hormones help regulate ovulation in women and in turn menstruation. Venous thromboembolism (VTE), stroke, and myocardial infarction are all risk factors when taking combined hormonal contraception due to the chemical composition of Ethinyl estradiol. Ethinyl estradiol’s binding mechanism to an estrogen receptor causes clots and therefore a risk for cardiovascular disease. The dosage of Ethinyl estradiol is related to an increased risk for VTE, stroke, and myocardial infarction. Due to the increased threat to cardiovascular health, physicians should screen patient health history carefully when prescribing combined hormonal birth control. Analyzing the risk Ethinyl estradiol poses to cardiovascular health in women can be used to determine if combined hormonal birth control is the ideal choice for contraception. 3 Effects Ethinyl Estradiol INTRODUCTION Birth control, a contraceptive, is frequently prescribed to women of varying ages throughout the United States. Birth control can be used for its primary use as a contraceptive or prescribed as a means of lessening symptoms of reproductive diseases, such as endometriosis. Birth control comes in various forms and methods. Intrauterine devices (IUDs) and birth control implants are forms which are implanted into the women and rely on the release of hormones to regulate the menstrual cycle (Planned Parenthood). -
Whole Egg Consumption Increases Gene Expression Within the Glutathione Pathway in the Liver of Zucker Diabetic Fatty Rats
Food Science and Human Nutrition Publications Food Science and Human Nutrition 11-3-2020 Whole egg consumption increases gene expression within the glutathione pathway in the liver of Zucker Diabetic Fatty rats Joe L. Webb Iowa State University Amanda E. Bries Iowa State University, [email protected] Brooke Vogel Iowa State University Claudia Carrillo Iowa State University, [email protected] Lily Harvison Iowa State University, [email protected] See next page for additional authors Follow this and additional works at: https://lib.dr.iastate.edu/fshn_hs_pubs Part of the Dietetics and Clinical Nutrition Commons, Endocrinology, Diabetes, and Metabolism Commons, Exercise Science Commons, Food Chemistry Commons, Human and Clinical Nutrition Commons, and the Molecular, Genetic, and Biochemical Nutrition Commons The complete bibliographic information for this item can be found at https://lib.dr.iastate.edu/ fshn_hs_pubs/38. For information on how to cite this item, please visit http://lib.dr.iastate.edu/ howtocite.html. This Article is brought to you for free and open access by the Food Science and Human Nutrition at Iowa State University Digital Repository. It has been accepted for inclusion in Food Science and Human Nutrition Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Whole egg consumption increases gene expression within the glutathione pathway in the liver of Zucker Diabetic Fatty rats Abstract Nutrigenomic evidence supports the idea that Type 2 Diabetes Mellitus (T2DM) arises due to the interactions between the transcriptome, individual genetic profiles, lifestyle, and diet. Since eggs are a nutrient dense food containing bioactive ingredients that modify gene expression, our goal was to examine the role of whole egg consumption on the transcriptome during T2DM. -
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! ""! ACKNOWLEDGEMENTS I dedicate this thesis to my parents who inspired me to become a scientist through invigorating scientific discussions at the dinner table even when I was too young to understand what the hippocampus was. They also prepared me for the ups and downs of science and supported me through all of these experiences. I would like to thank my advisor Dr. Elizabeth Blackburn and my thesis committee members Dr. Eric Verdin, and Dr. Emmanuelle Passegue. Liz created a nurturing and supportive environment for me to explore my own ideas, while at the same time teaching me how to love science, test my questions, and of course provide endless ways to think about telomeres and telomerase. Eric and Emmanuelle both gave specific critical advice about the proper experiments for T cells and both volunteered their lab members for further critical advice. I always felt inspired with a sense of direction after thesis committee meetings. The Blackburn lab is full of smart and dedicated scientists whom I am thankful for their support. Specifically Dr. Shang Li and Dr. Brad Stohr for their stimulating scientific debates and “arguments.” Dr. Jue Lin, Dana Smith, Kyle Lapham, Dr. Tet Matsuguchi, and Kyle Jay for their friendships and discussions about what my data could possibly mean. Dr. Eva Samal for teaching me molecular biology techniques and putting up with my late night lab exercises. Beth Cimini for her expertise with microscopy, FACs, singing, and most of all for being a caring and supportive friend. Finally, I would like to thank Dr. Imke Listerman, my scientific partner for most of the breast cancer experiments. -
The Inverse Agonist DG172 Triggers a Pparβ/Δ-Independent Myeloid Lineage Shift and Promotes GM-CSF/IL-4-Induced Dendritic Cell Differentiation
Downloaded from molpharm.aspetjournals.org at ASPET Journals on September 26, 2021 1 MOL #94672 #94672 MOL -independent myeloid lineage shift and -independent myeloid lineage δ / β nagel, Wolfgang Meissner, Gavin Giehl, Cornelia Giehl, Cornelia Gavin Wolfgang Meissner, nagel, This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. -
Routes of Oxytocin Administration for the Prevention of Postpartum Haemorrhage After Vaginal Birth
WHO recommendation on Routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth WHO recommendation on Routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth WHO recommendation on routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth ISBN 978-92-4-001392-6 (electronic version) ISBN 978-92-4-001393-3 (print version) © World Health Organization 2020 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/ licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/ mediation/rules/). -
Chebi: a Chemistry Ontology and Database
de Matos et al. Journal of Cheminformatics 2010, 2(Suppl 1):P6 http://www.jcheminf.com/content/2/S1/P6 POSTER PRESENTATION Open Access ChEBI: a chemistry ontology and database Paula de Matos*, A Dekker, M Ennis, Janna Hastings, K Haug, S Turner, Christoph Steinbeck From 5th German Conference on Cheminformatics: 23. CIC-Workshop Goslar, Germany. 8-10 November 2009 The bioinformatics community has developed a policy and identifier. A complete version is available with all of open access and open data since its inception. This is the ChEBI data properties such as synonyms, cross- contrary to chemoinformatics which has traditionally references, SMILES and InChI. Furthermore cross-refer- been a closed-access area. In 2004, two complementary ences in ChEBI have been extended to include BRENDA open access databases were initiated by the bioinfor- the enzyme database, NMRShiftDB the database for matics community, ChEBI [1] and PubChem. PubChem organic structures and their nuclear magnetic resonance serves as automated repository on the biological activ- (nmr) spectra, Rhea the biochemical reaction database ities of small molecules and ChEBI (Chemical Entities of and IntEnz the enzyme nomenclature database. Biological Interest) as a manually annotated database of ChEBI is available at http://www.ebi.ac.uk/chebi. molecular entities focused on ‘small’ chemical com- pounds. Although ChEBI is reasonably compact contain- Published: 4 May 2010 ing just over 18,000 entities, it provides a wide range of data items such as chemical nomenclature, an ontology References and chemical structures. The ChEBI database has a 1. Degtyarenko K, de Matos P, Ennis M, Hastings J, Zbinden M, McNaught A, strong focus on quality with exceptional efforts afforded Alcántara R, Darsow M, Guedj M, Ashburner M: ChEBI: a database and ontology for chemical entities of biological interest. -
Inchi in the Wild: an Assessment of Inchikey Searching in Google Christopher Southan
Southan Journal of Cheminformatics 2013, 5:10 http://www.jcheminf.com/content/5/1/10 REVIEW Open Access InChI in the wild: an assessment of InChIKey searching in Google Christopher Southan Abstract While chemical databases can be queried using the InChI string and InChIKey (IK) the latter was designed for open- web searching. It is becoming increasingly effective for this since more sources enhance crawling of their websites by the Googlebot and consequent IK indexing. Searchers who use Google as an adjunct to database access may be less familiar with the advantages of using the IK as explored in this review. As an example, the IK for atorvastatin retrieves ~200 low-redundancy links from a Google search in 0.3 of a second. These include most major databases and a very low false-positive rate. Results encompass less familiar but potentially useful sources and can be extended to isomer capture by using just the skeleton layer of the IK. Google Advanced Search can be used to filter large result sets. Image searching with the IK is also effective and complementary to open-web queries. Results can be particularly useful for less-common structures as exemplified by a major metabolite of atorvastatin giving only three hits. Testing also demonstrated document-to-document and document-to-database joins via structure matching. The necessary generation of an IK from chemical names can be accomplished using open tools and resources for patents, papers, abstracts or other text sources. Active global sharing of local IK-linked information can be accomplished via surfacing in open laboratory notebooks, blogs, Twitter, figshare and other routes. -
The EPA Comptox Dashboard and Underpinning Software Architecture – a Platform for Data Integration for Environmental Chemistry
http://www.orcid.org/0000-0002-2668-4821 The EPA CompTox Chemistry Dashboard and Underpinning Software Architecture – a platform for data integration for environmental chemistry data Antony Williams1, Chris Grulke1, Daniel Chang2, Kristan Markey2 and Jeff Edwards1 1. National Center for Computational Toxicology, U.S. Environmental Protection Agency, RTP, NC 2. Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency, Washington, DC 3. Office of Science Coordination and Policy, U.S. Environmental Protection Agency, Washington, DC The views expressed in this presentation are those of the author and do not necessarily reflect the views or policies of the U.S. EPA August 2017 ACS Fall Meeting, Washington, DC The CompTox Chemistry Dashboard PRIMARY GOALS • Deliver a web-based application serving up the chemistry related data used by our team • Provide public access to the results of over a decade of curation work reviewing environmental chemistry data • Provide access to the results of our QSAR modeling work • Deliver a central hub to link together websites of interest • All data to be available as Open Data for download/reuse SECONDARY GOAL • Develop a cheminformatics architecture to serve as a high quality chemical foundation for all NCCT tools and data The CompTox Chemistry Dashboard: An Overview • A publicly accessible website delivering access: – ~760,000 chemicals and related property data – Links to other agency websites and public data resources – “Literature” searches for chemicals using public resources – Integration -
Investigating the Impact of Telomere Dysfunction on the Chronic Lymphocytic Leukaemia Genome
INVESTIGATING THE IMPACT OF TELOMERE DYSFUNCTION ON THE CHRONIC LYMPHOCYTIC LEUKAEMIA GENOME Laura Escudero-Monreal A thesis submitted for the degree of Doctor of Philosophy September 2017 Institute of Cancer and Genetics School of Medicine Cardiff University Funded by Cancer Research Wales and Cardiff University I dedicate this Ph.D. thesis to everyone who suffers from cancer, for I hope one day, science can fight and win this battle. Laura Escudero-Monreal NOTICE OF SUBMISSION DECLARATION This work has not been submitted in substance for any other degree or award at this or any other university or place of learning, nor is being submitted concurrently in candidature for any degree or other award. Signed: Date: STATEMENT 1 This thesis is being submitted in partial fulfilment of the requirements for the degree of PhD. Signed: Date: STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated, and the thesis has not been edited by a third party beyond what is permitted by Cardiff University’s Policy on the Use of Third Party Editors by Research Degree Students. Other sources are acknowledged by explicit references. The views expressed are my own. Signed: Date: STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loan, and for the title and summary to be made available to outside organisations. Signed: Date: STATEMENT 4: PREVIOUSLY APPROVED BAR ON ACCESS I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loans after expiry of a bar on access previously approved by the Academic Standards & Quality Committee.