Metals from Cell to Environment: Connecting Metallomics with Other Omics
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Research Article Effects of Trace Metal Profiles Characteristic for Autism on Synapses in Cultured Neurons
Hindawi Publishing Corporation Neural Plasticity Volume 2015, Article ID 985083, 16 pages http://dx.doi.org/10.1155/2015/985083 Research Article Effects of Trace Metal Profiles Characteristic for Autism on Synapses in Cultured Neurons Simone Hagmeyer,1 Katharina Mangus,1 Tobias M. Boeckers,2 and Andreas M. Grabrucker1,2 1 WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, 89081 Ulm, Germany 2Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany Correspondence should be addressed to Andreas M. Grabrucker; [email protected] Received 9 December 2014; Revised 19 January 2015; Accepted 19 January 2015 Academic Editor: Lucas Pozzo-Miller Copyright © 2015 Simone Hagmeyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Various recent studies revealed that biometal dyshomeostasis plays a crucial role in the pathogenesis of neurological disorders such as autism spectrum disorders (ASD). Substantial evidence indicates that disrupted neuronal homeostasis of different metal ions such as Fe, Cu, Pb, Hg, Se, and Zn may mediate synaptic dysfunction and impair synapse formation and maturation. Here, we performed in vitro studies investigating the consequences of an imbalance of transition metals on glutamatergic synapses of hippocampal neurons. We analyzed whether an imbalance of any one metal ion alters cell health and synapse numbers. Moreover, we evaluated whether a biometal profile characteristic for ASD patients influences synapse formation, maturation, and composition regarding NMDA receptor subunits and Shank proteins. Our results show that an ASD like biometal profile leads to a reduction of NMDAR (NR/Grin/GluN) subunit 1 and 2a, as well as Shank gene expression along with a reduction of synapse density. -
Characterization of Biometal Profiles in Neurological Disorders
Metallomics Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/metallomics Page 1 of 15 Metallomics 1 2 3 Table of contents entry 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 This review summarizes findings of dysregulations of metal-ions in neurological diseases and 19 tries to develop and predict specific biometal profiles. 20 21 22 23 24 25 Manuscript 26 27 28 29 30 31 32 33 34 35 Accepted 36 37 38 39 40 41 42 43 44 45 46 47 Metallomics 48 49 50 51 52 53 54 55 56 57 58 59 60 Metallomics Page 2 of 15 1 2 Metallomics RSC Publishing 3 4 5 Critical Review 6 7 8 9 Characterization of biometal - profiles in neurological 10 disorders 11 Cite this: DOI: 10.1039/x0xx00000x 12 a a,b# 13 Stefanie Pfaender and Andreas M. -
Canonical Biochemistry and Molecular Biology of Petrobactin from Bacillus Anthracis
Molecular Microbiology (2016) 102(2), 196–206 doi:10.1111/mmi.13465 First published online 9 August 2016 MicroReview Flying under the radar: The non-canonical biochemistry and molecular biology of petrobactin from Bacillus anthracis A.K. Hagan,1 P.E. Carlson Jr2 and P.C. Hanna1* major gaps in our understanding of the petrobactin 1Department of Microbiology and Immunology, iron acquisition system, some projected means for University of Michigan Medical School, 1150 W. exploiting current knowledge, and potential future Medical Center Drive, 6703 Medical Science Building research directions. II, Ann Arbor, MI 48109. 2Laboratory of Mucosal Pathogens and Cellular Immunity, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Introduction Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 52/72; Rm 3306, Iron is the fourth most abundant element on earth and Silver Spring, MD 20993. almost all living organisms require iron’s redox proper- ties for life. However, these same properties can be toxic for cells, necessitating biological solutions to bal- ance acquisition with stringent regulation (Wandersman Summary and Delepelaire, 2004; Miethke and Marahiel, 2007). The dramatic, rapid growth of Bacillus anthracis that The roles of iron as an enzyme cofactor and in electron occurs during systemic anthrax implies a crucial transfer are a double-edged sword. High, unregulated requirement for the efficient acquisition of iron. While quantities of iron in the cell are toxic due to the Fenton recent advances in our understanding of B. anthracis reaction in which oxidation of ferrous iron generates iron acquisition systems indicate the use of strat- superoxide radicals resulting in DNA damage (Wanders- egies similar to other pathogens, this review focuses man and Delepelaire, 2004; Miethke and Marahiel, on unique features of the major siderophore system, 2007). -
Metatranscriptomic Analysis of Community Structure And
School of Environmental Sciences Metatranscriptomic analysis of community structure and metabolism of the rhizosphere microbiome by Thomas Richard Turner Submitted in partial fulfilment of the requirement for the degree of Doctor of Philosophy, September 2013 This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that use of any information derived there from must be in accordance with current UK Copyright Law. In addition, any quotation or extract must include full attribution. i Declaration I declare that this is an account of my own research and has not been submitted for a degree at any other university. The use of material from other sources has been properly and fully acknowledged, where appropriate. Thomas Richard Turner ii Acknowledgements I would like to thank my supervisors, Phil Poole and Alastair Grant, for their continued support and guidance over the past four years. I’m grateful to all members of my lab, both past and present, for advice and friendship. Graham Hood, I don’t know how we put up with each other, but I don’t think I could have done this without you. Cheers Salt! KK, thank you for all your help in the lab, and for Uma’s biryanis! Andrzej Tkatcz, thanks for the useful discussions about our projects. Alison East, thank you for all your support, particularly ensuring Graham and I did not kill each other. I’m grateful to Allan Downie and Colin Murrell for advice. For sequencing support, I’d like to thank TGAC, particularly Darren Heavens, Sophie Janacek, Kirsten McKlay and Melanie Febrer, as well as John Walshaw, Mark Alston and David Swarbreck for bioinformatic support. -
Advances in Enzyme Biotechnology Advances in Enzyme Biotechnology
Pratyoosh Shukla Brett I. Pletschke Editors Advances in Enzyme Biotechnology Advances in Enzyme Biotechnology Pratyoosh Shukla • Brett I. Pletschke Editors Advances in Enzyme Biotechnology Editors Pratyoosh Shukla Brett I. Pletschke Department of Microbiology Department of Biochemistry, Maharshi Dayanand University Microbiology and Biotechnology Rohtak, Haryana , India Rhodes University Grahamstown, South Africa ISBN 978-81-322-1093-1 ISBN 978-81-322-1094-8 (eBook) DOI 10.1007/978-81-322-1094-8 Springer New Delhi Heidelberg New York Dordrecht London Library of Congress Control Number: 2013945175 © Springer India 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. -
The Metallome As a Link Between the ``Omes'' in Autism Spectrum
fnmol-14-695873 June 29, 2021 Time: 18:33 # 1 MINI REVIEW published: 05 July 2021 doi: 10.3389/fnmol.2021.695873 The Metallome as a Link Between the “Omes” in Autism Spectrum Disorders Janelle E. Stanton1,2, Sigita Malijauskaite2,3, Kieran McGourty2,3,4 and Andreas M. Grabrucker1,2,4* 1 Department of Biological Sciences, University of Limerick, Limerick, Ireland, 2 Bernal Institute, University of Limerick, Limerick, Ireland, 3 Department of Chemical Sciences, University of Limerick, Limerick, Ireland, 4 Health Research Institute, University of Limerick, Limerick, Ireland Metal dyshomeostasis plays a significant role in various neurological diseases such as Alzheimer’s disease, Parkinson’s disease, Autism Spectrum Disorders (ASD), and many more. Like studies investigating the proteome, transcriptome, epigenome, microbiome, etc., for years, metallomics studies have focused on data from their domain, i.e., trace metal composition, only. Still, few have considered the links between other “omes,” which may together result in an individual’s specific pathologies. In particular, ASD have been reported to have multitudes of possible causal effects. Metallomics Edited by: data focusing on metal deficiencies and dyshomeostasis can be linked to functions David Blum, INSERM U1172 Centre de Recherche of metalloenzymes, metal transporters, and transcription factors, thus affecting the Jean Pierre Aubert, France proteome and transcriptome. Furthermore, recent studies in ASD have emphasized Reviewed by: the gut-brain axis, with alterations in the microbiome being linked to changes in the Arnaud B. Nicot, metabolome and inflammatory processes. However, the microbiome and other “omes” INSERM U1064 Centre de Recherche en Transplantation et Immunologie, are heavily influenced by the metallome. -
UNIVERSITY of CALIFORNIA Los Angeles Cloud-Based Analysis And
UNIVERSITY OF CALIFORNIA Los Angeles Cloud-based Analysis and Integration of Proteomics and Metabolomics Datasets A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics by Jeong Ho (Howard) Choi 2019 © Copyright by Jeong Ho (Howard) Choi 2019 ABSTRACT OF THE DISSERTATION Cloud-based Analysis and Integration of Proteomics and Metabolomics Datasets by Jeong Ho (Howard) Choi Doctor of Philosophy in Bioinformatics University of California, Los Angeles, 2019 Professor Peipei Ping, Chair Our capabilities to define cardiovascular health and disease using highly multivariate “omics” datasets have substantially increased in recent years. Advances in acquisition technologies as well as bioinformatics methods have paved the way for ultimately resolving every biomolecule comprising various human “omes”. Understanding how different “omes” change and interact with one another temporally will ultimately unveil multi-omic molecular signatures that inform pathologic mechanisms, indicate disease phenotypes, and identify new therapeutic targets. Herein we describe a thesis project that creates novel, contemporary data science methods and workflows to extract temporal molecular signatures of disease from multi-omics analyses, and develops integrated omics knowledgebases for the cardiovascular community at-large. Chapter 1 provides an overview of cardiac physiology and pathophysiology involved in cardiac remodeling and heart failure (HF). A description of the systematic characterization of cardiac proteomes and metabolomes is included, including methodologies for multi-omics phenotyping. Finally, an overview of bioinformatics methods for driver molecule discovery is provided, discussing strategies for characterizing temporal patterns and conducting functional enrichment. ii Chapter 2 describes computational approaches to discern the oxidative posttranslational modification (O-PTM) proteome, an important factor in cardiac remodeling. -
(12) United States Patent (10) Patent No.: US 9,689,046 B2 Mayall Et Al
USOO9689046B2 (12) United States Patent (10) Patent No.: US 9,689,046 B2 Mayall et al. (45) Date of Patent: Jun. 27, 2017 (54) SYSTEM AND METHODS FOR THE FOREIGN PATENT DOCUMENTS DETECTION OF MULTIPLE CHEMICAL WO O125472 A1 4/2001 COMPOUNDS WO O169245 A2 9, 2001 (71) Applicants: Robert Matthew Mayall, Calgary (CA); Emily Candice Hicks, Calgary OTHER PUBLICATIONS (CA); Margaret Mary-Flora Bebeselea, A. et al., “Electrochemical Degradation and Determina Renaud-Young, Calgary (CA); David tion of 4-Nitrophenol Using Multiple Pulsed Amperometry at Christopher Lloyd, Calgary (CA); Lisa Graphite Based Electrodes', Chem. Bull. “Politehnica” Univ. Kara Oberding, Calgary (CA); Iain (Timisoara), vol. 53(67), 1-2, 2008. Fraser Scotney George, Calgary (CA) Ben-Yoav. H. et al., “A whole cell electrochemical biosensor for water genotoxicity bio-detection”. Electrochimica Acta, 2009, 54(25), 6113-6118. (72) Inventors: Robert Matthew Mayall, Calgary Biran, I. et al., “On-line monitoring of gene expression'. Microbi (CA); Emily Candice Hicks, Calgary ology (Reading, England), 1999, 145 (Pt 8), 2129-2133. (CA); Margaret Mary-Flora Da Silva, P.S. et al., “Electrochemical Behavior of Hydroquinone Renaud-Young, Calgary (CA); David and Catechol at a Silsesquioxane-Modified Carbon Paste Elec trode'. J. Braz. Chem. Soc., vol. 24, No. 4, 695-699, 2013. Christopher Lloyd, Calgary (CA); Lisa Enache, T. A. & Oliveira-Brett, A. M., "Phenol and Para-Substituted Kara Oberding, Calgary (CA); Iain Phenols Electrochemical Oxidation Pathways”, Journal of Fraser Scotney George, Calgary (CA) Electroanalytical Chemistry, 2011, 1-35. Etesami, M. et al., “Electrooxidation of hydroquinone on simply prepared Au-Pt bimetallic nanoparticles'. Science China, Chem (73) Assignee: FREDSENSE TECHNOLOGIES istry, vol. -
Zinc Complexes with Nitrogen Donor Ligands As Anticancer Agents
molecules Review Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents Marina Porchia 1,* , Maura Pellei 2,* , Fabio Del Bello 3 and Carlo Santini 2 1 ICMATE-C.N.R., Corso Stati Uniti 4, 35127 Padova, Italy 2 Chemistry Division, School of Science and Technology, University of Camerino, via S. Agostino 1, 62032 Camerino, Italy; [email protected] 3 Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy; [email protected] * Correspondence: [email protected] (M.P.); [email protected] (M.P.) Academic Editor: Kogularamanan Suntharalingam Received: 7 November 2020; Accepted: 7 December 2020; Published: 9 December 2020 Abstract: The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. -
The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders
Hindawi Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 8210734, 18 pages https://doi.org/10.1155/2017/8210734 Review Article The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders 1,2 1,2 Michal Pokusa and Alžbeta Kráľová Trančíková 1Jessenius Faculty of Medicine in Martin, Biomedical Center Martin JFM CU, Comenius University in Bratislava, Bratislava, Slovakia 2Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Bratislava, Slovakia Correspondence should be addressed to Alžbeta Kráľová Trančíková; [email protected] Received 24 February 2017; Revised 19 May 2017; Accepted 28 May 2017; Published 2 July 2017 Academic Editor: Rhian Touyz Copyright © 2017 Michal Pokusa and Alžbeta Kráľová Trančíková. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Traditionally, oxidative stress as a biological aspect is defined as an imbalance between the free radical generation and antioxidant capacity of living systems. The intracellular imbalance of ions, disturbance in membrane dynamics, hypoxic conditions, and dysregulation of gene expression are all molecular pathogenic mechanisms closely associated with oxidative stress and underpin systemic changes in the body. These also include aspects such as chronic immune system activation, the impairment of cellular structure renewal, and alterations in the character of the endocrine secretion of diverse tissues. All of these mentioned features are crucial for the correct function of the various tissue types in the body. In the present review, we summarize current knowledge about the common roots of metabolic and neurodegenerative disorders induced by oxidative stress. -
How Do Bacterial Cells Ensure That Metalloproteins Get the Correct Metal?
REVIEWS How do bacterial cells ensure that metalloproteins get the correct metal? Kevin J. Waldron and Nigel J. Robinson Abstract | Protein metal-coordination sites are richly varied and exquisitely attuned to their inorganic partners, yet many metalloproteins still select the wrong metals when presented with mixtures of elements. Cells have evolved elaborate mechanisms to scavenge for sufficient metal atoms to meet their needs and to adjust their needs to match supply. Metal sensors, transporters and stores have often been discovered as metal-resistance determinants, but it is emerging that they perform a broader role in microbial physiology: they allow cells to overcome inadequate protein metal affinities to populate large numbers of metalloproteins with the right metals. It has been estimated that one-quarter to one-third of all Both monovalent (cuprous) copper, which is expected proteins require metals, although the exploitation of ele- to predominate in a reducing cytosol, and trivalent ments varies from cell to cell and has probably altered over (ferric) iron, which is expected to predominate in an the aeons to match geochemistry1–3 (BOX 1). The propor- oxidizing periplasm, are also highly competitive, as are tions have been inferred from the numbers of homologues several non-essential metals, such as cadmium, mercury of known metalloproteins, and other deduced metal- and silver6 (BOX 2). How can a cell simultaneously contain binding motifs, encoded within sequenced genomes. A some proteins that require copper or zinc and others that large experimental estimate was generated using native require uncompetitive metals, such as magnesium or polyacrylamide-gel electrophoresis of extracts from iron- manganese? In a most simplistic model in which pro- rich Ferroplasma acidiphilum followed by the detection of teins pick elements from a cytosol in which all divalent metal in protein spots using inductively coupled plasma metals are present and abundant, all proteins would bind mass spectrometry4. -
Biochemical Studies on Redox Regulation in Different Dormancy Models of Mycobacteria
Biochemical Studies on Redox Regulation in Different Dormancy Models of Mycobacteria Thesis Submitted to Savitribai Phule Pune University For The Degree Of DOCTOR OF PHILOSOPHY IN BIOTECHNOLOGY By Ketaki Dilip Shurpali Research Supervisor Dr. Dhiman Sarkar Combichem Bioresource Center Organic Chemistry Division CSIR-National Chemical Laboratory Pune-411008 India October 2014 Certificate This is to certify that the work incorporated in the thesis entitled “ Biochemical Studies on Redox Regulation in Different Dormancy Models of Mycobacteria ” submitted by Ketaki Dilip Shurpali was carried out under my supervision at Combichem Bioresource Center, Organic Chemistry Division, National Chemical Laboratory, Pune-411008, Maharashtra, India. Materials obtained from other sources have been duly acknowledged in the thesis. Dr. Dhiman Sarkar (Research Guide) I Declaration by Research Scholar I hereby declare that the thesis entitled " Biochemical Studies on Redox Regulation in Different Dormancy Models of Mycobacteria ", submitted for the Degree of Doctor of Philosophy to the Savitribai Phule Pune University, has been carried out by me at Combichem Bioresource Center, Organic Chemistry Division, CSIR-National Chemical Laboratory, Pune-411008, Maharashtra, India, under the supervision of Dr. Dhiman Sarkar (Research supervisor). The work is original and has not been submitted in part or full by me for any other degree or diploma to any other University. Ketaki Dilip Shurpali (Research Scholar) II Dedications This thesis is dedicated to all those people who were always besides me in my good and bad times. First dedication goes to my father Mr. Dilip Shurpali and mother Mrs. Devyani Shurpali who instilled in me the desire to learn new things and confidence to achieve my dreams.