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1. Case Report: Pediatric Patient with COVID-19 and Multisystem Inflammatory Syndrome in Children

Author

MacKenzie W. Burger, Marcus A. Moore, and John M. Wilburn

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Introduction: Coronavirus disease 2019 (COVID-19) rarely manifests with severe complications in pediatric patients. An association between COVID-19 and a Kawasaki-like inflammatory syndrome has recently presented in pediatric patients. Case Report: We report a unique case of multisystem inflammatory syndrome in children presenting with characteristic findings in a child who later developed cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. Conclusion: Recognition of these early signs and symptoms facilitates screening and risk stratification of pediatric COVID-19 cases associated with increased morbidity.

Published
2020
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2. Comparative Genomics and Metabolomics Analyses of Clavulanic Acid-Producing Streptomyces Species Provides Insight Into Specialized Metabolism

Author

Nader F. AbuSara, Brandon M. Piercey, Marcus A. Moore, Arshad Ali Shaikh, Louis-Félix Nothias, Santosh K. Srivastava, Pablo Cruz-Morales, Pieter C. Dorrestein, Francisco Barona-Gómez, and Kapil Tahlan

Subjects
Streptomyces, specialized metabolism, metabolomics, genomics, gene clusters, β-lactams, Microbiology, QR1-502
Abstract

Clavulanic acid is a bacterial specialized metabolite, which inhibits certain serine β-lactamases, enzymes that inactivate β-lactam antibiotics to confer resistance. Due to this activity, clavulanic acid is widely used in combination with penicillin and cephalosporin (β-lactam) antibiotics to treat infections caused by β-lactamase-producing bacteria. Clavulanic acid is industrially produced by fermenting Streptomyces clavuligerus, as large-scale chemical synthesis is not commercially feasible. Other than S. clavuligerus, Streptomyces jumonjinensis and Streptomyces katsurahamanus also produce clavulanic acid along with cephamycin C, but information regarding their genome sequences is not available. In addition, the Streptomyces contain many biosynthetic gene clusters thought to be “cryptic,” as the specialized metabolites produced by them are not known. Therefore, we sequenced the genomes of S. jumonjinensis and S. katsurahamanus, and examined their metabolomes using untargeted mass spectrometry along with S. clavuligerus for comparison. We analyzed the biosynthetic gene cluster content of the three species to correlate their biosynthetic capacities, by matching them with the specialized metabolites detected in the current study. It was recently reported that S. clavuligerus can produce the plant-associated metabolite naringenin, and we describe more examples of such specialized metabolites in extracts from the three Streptomyces species. Detailed comparisons of the biosynthetic gene clusters involved in clavulanic acid (and cephamycin C) production were also performed, and based on our analyses, we propose the core set of genes responsible for producing this medicinally important metabolite.

Published
2019
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3. Effects of the energy balance transition on bone mass and strength

Author

Ian J. Wallace, Christopher Toya, Mario Antonio Peña Muñoz, Jana Valesca Meyer, Taylor Busby, Adam Z. Reynolds, Jordan Martinez, Travis Torres Thompson, Marcus Miller-Moore, Alexandra R. Harris, Roberto Rios, Alexis Martinez, Tea Jashashvili, and Christopher B. Ruff

Subjects
Medicine, Science
Abstract

Abstract Chronic positive energy balance has surged among societies worldwide due to increasing dietary energy intake and decreasing physical activity, a phenomenon called the energy balance transition. Here, we investigate the effects of this transition on bone mass and strength. We focus on the Indigenous peoples of New Mexico in the United States, a rare case of a group for which data can be compared between individuals living before and after the start of the transition. We show that since the transition began, bone strength in the leg has markedly decreased, even though bone mass has apparently increased. Decreased bone strength, coupled with a high prevalence of obesity, has resulted in many people today having weaker bones that must sustain excessively heavy loads, potentially heightening their risk of a bone fracture. These findings may provide insight into more widespread upward trends in bone fragility and fracture risk among societies undergoing the energy balance transition.

Published
2023
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4. A brief history of Canadian freeze-dried blood products: Ingenuity, collaboration, and leadership

Author

Marcus A. Moore and Andrew Beckett

Subjects
General Medicine
Abstract

LAY SUMMARY During the Second World War, Canada became a leader in the development and production of products used to treat shock, particularly shock caused by massive bleeds. Canada started the first blood service in response to the need for blood products overseas. This was done in the form of freeze-dried serum, which is made up of fluid-based proteins extracted from blood. Freeze-dried serum could be stored indefinitely and was lightweight, hardy, and easy to deliver both to the battlefield and to the patient. Freeze-dried serum could be provided to patients in shock as a result of losing a large volume of blood. Unfortunately, after the war, freeze-dried blood products fell out of favour over concerns about viral hepatitis. Recently, freeze-dried blood products have enjoyed a renaissance, and Canada is currently developing a new product to meet the challenges of remote resuscitation.

Published
2022
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5. δ-(<scp>l</scp>-α-aminoadipyl)-<scp>l</scp>-cysteinyl-<scp>d</scp>-valine synthetase (ACVS): discovery and perspectives

Author

Kapil Tahlan, Marcus A. Moore, and Susan E. Jensen

Subjects
0301 basic medicine, Stereochemistry, viruses, ACV synthetase, Genes, Fungal, Bioengineering, Tripeptide, Penicillium chrysogenum, Biology, Applied Microbiology and Biotechnology, Streptomyces, 03 medical and health sciences, Bacterial Proteins, Valine, β lactams, Protein purification, Peptide Synthases, skin and connective tissue diseases, chemistry.chemical_classification, 030102 biochemistry & molecular biology, virus diseases, biology.organism_classification, 030104 developmental biology, Enzyme, Biochemistry, chemistry, Genes, Bacterial, biology.protein, Oligopeptides, Large size, Biotechnology
Abstract

The δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine (ACV) tripeptide is the first dedicated intermediate in the biosynthetic pathway leading to the penicillin and cephalosporin classes of β-lactam natural products in bacteria and fungi. It is synthesized nonribosomally by the ACV synthetase (ACVS) enzyme, which has been purified and partially characterized from many sources. Due to its large size and instability, many details regarding the reaction mechanism of ACVS are still not fully understood. In this review we discuss the chronology and associated methodology that led to the discovery of ACVS, some of the main findings regarding its activities, and some recent/current studies being conducted on the enzyme. In addition, we conclude with perspectives on what can be done to increase our understating of this very important protein in the future.

Published
2017
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6. Comparative Genomics and Metabolomics Analyses of Clavulanic Acid-Producing Streptomyces Species Provides Insight Into Specialized Metabolism

Author

Marcus A. Moore, Santosh Kumar Srivastava, Pieter C. Dorrestein, Francisco Barona-Gómez, Pablo Cruz-Morales, Brandon M. Piercey, Louis-Félix Nothias, Kapil Tahlan, Nader F. AbuSara, and Arshad Ali Shaikh

Subjects
Microbiology (medical), gene clusters, Metabolite, lcsh:QR1-502, Streptomyces clavuligerus, Microbiology, Streptomyces, lcsh:Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, Clavulanic acid, Gene cluster, specialized metabolism, genomics, medicine, 030304 developmental biology, Comparative genomics, 0303 health sciences, biology, 030306 microbiology, Chemistry, β-lactams, biology.organism_classification, metabolomics, Biochemistry, Bacteria, medicine.drug
Abstract

Clavulanic acid is a bacterial specialized metabolite, which inhibits certain serine β-lactamases, enzymes that inactivate β-lactam antibiotics to confer resistance. Due to this activity, clavulanic acid is widely used in combination with penicillin and cephalosporin (β-lactam) antibiotics to treat infections caused by β-lactamase-producing bacteria. Clavulanic acid is industrially produced by fermenting Streptomyces clavuligerus, as large-scale chemical synthesis is not commercially feasible. Other than S. clavuligerus, Streptomyces jumonjinensis and Streptomyces katsurahamanus also produce clavulanic acid along with cephamycin C, but information regarding their genome sequences is not available. In addition, the Streptomyces contain many biosynthetic gene clusters thought to be “cryptic,” as the specialized metabolites produced by them are not known. Therefore, we sequenced the genomes of S. jumonjinensis and S. katsurahamanus, and examined their metabolomes using untargeted mass spectrometry along with S. clavuligerus for comparison. We analyzed the biosynthetic gene cluster content of the three species to correlate their biosynthetic capacities, by matching them with the specialized metabolites detected in the current study. It was recently reported that S. clavuligerus can produce the plant-associated metabolite naringenin, and we describe more examples of such specialized metabolites in extracts from the three Streptomyces species. Detailed comparisons of the biosynthetic gene clusters involved in clavulanic acid (and cephamycin C) production were also performed, and based on our analyses, we propose the core set of genes responsible for producing this medicinally important metabolite.

Published
2019
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7. Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus

Author

Kapil Tahlan, Nicole L Ferguson, Dawn R. D. Bignell, Marcus A. Moore, and Lourdes Peña-Castillo

Subjects
Proteomics, 0301 basic medicine, Proteome, 030106 microbiology, Streptomyces clavuligerus, Bioengineering, Applied Microbiology and Biotechnology, Streptomyces, 03 medical and health sciences, Bacterial Proteins, Clavulanic acid, medicine, Codon, Secondary metabolism, Gene, Beta-Lactamase Inhibitors, Clavulanic Acid, biology, Translation (biology), Gene Expression Regulation, Bacterial, biology.organism_classification, 3. Good health, Biochemistry, beta-Lactamase Inhibitors, Biotechnology, medicine.drug
Abstract

The genus Streptomyces comprises bacteria that undergo a complex developmental life cycle and produce many metabolites of importance to industry and medicine. Streptomyces clavuligerus produces the β-lactamase inhibitor clavulanic acid, which is used in combination with β-lactam antibiotics to treat certain β-lactam resistant bacterial infections. Many aspects of how clavulanic acid production is globally regulated in S. clavuligerus still remains unknown. We conducted comparative proteomics analysis using the wild type strain of S. clavuligerus and two mutants (ΔbldA and ΔbldG), which are defective in global regulators and vary in their ability to produce clavulanic acid. Approximately 33.5 % of the predicted S. clavuligerus proteome was detected and 192 known or putative regulatory proteins showed statistically differential expression levels in pairwise comparisons. Interestingly, the expression of many proteins whose corresponding genes contain TTA codons (predicted to require the bldA tRNA for translation) was unaffected in the bldA mutant.

Published
2016
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8. Minimum Information about a Biosynthetic Gene cluster

Author

Patrick Caffrey, Renzo Kottmann, Eriko Takano, Sean Doyle, Axel A. Brakhage, Matthew Cummings, Juan Pablo Gomez-Escribano, Yvonne Mast, Ryan F. Seipke, Rob Lavigne, Markus Nett, Hans-Wilhelm Nützmann, Jan Claesen, David H. Sherman, Daniel Petras, Pablo Cruz-Morales, Carl J. Balibar, Anne Osbourn, Oscar P. Kuipers, Leonilde M. Moreira, Xinyu Liu, Marcia S. Osburne, Bohdan Ostash, David P. Fewer, Changsheng Zhang, Pelin Yilmaz, Mohamed S. Donia, Anja Greule, Hyun Uk Kim, Nicholas J. Tobias, Frank Oliver Glöckner, Christoph Geiger, Chia Y. Lee, William H. Gerwick, Philipp Wiemann, Bertolt Gust, Susan E. Jensen, Wilfred A. van der Donk, Jan Kormanec, Ben Shen, Christopher M. Thomas, Jason Micklefield, Srikanth Duddela, R. Cameron Coates, René De Mot, Anthony S. Haines, Neha Garg, Guohui Pan, Roderich D. Süssmuth, Hyung Jin Kwon, Jonathan D. Walton, Lena Gerwick, Jörn Piel, Monika Ehling-Schulz, Zhenhua Tian, Jonathan L. Klassen, Xiaohui Yan, Emily A. Monroe, Yunchang Xie, Russell J. Cox, Keishi Ishida, Grace Yim, Stefano Donadio, Nadine Ziemert, Yuta Tsunematsu, Matthew L. Hillwig, Miroslav Petricek, Sylvie Lautru, Tilmann Weber, Andrew W. Truman, Rainer Breitling, Peter Kötter, Nikos C. Kyrpides, Stephanie Düsterhus, Christian Hertweck, Hideaki Oikawa, Sean F. Brady, Christopher T. Walsh, Adam C. Jones, Marcus A. Moore, Bradley S. Moore, Barrie Wilkinson, Simone M. Mantovani, Nathan A. Moss, Elizabeth E. Wyckoff, Emily P. Balskus, Kapil Tahlan, Fengan Yu, Monica Höfte, Jos M. Raaijmakers, Taifo Mahmud, Yit-Heng Chooi, Yi Tang, Andreas Bechthold, Douglas A. Mitchell, Joanne M. Willey, Helge B. Bode, John B. Biggins, Margherita Sosio, Yi-Qiang Cheng, Carmen Méndez, Leonard Kaysser, Joleen Masschelein, Daniel Krug, Federico Rosconi, Marnix H. Medema, Kaarina Sivonen, Tomohisa Kuzuyama, Mikko Metsä-Ketelä, Esther K. Schmitt, Carsten Kegler, Andriy Luzhetskyy, Gilles P. van Wezel, Bai Linquan, Kai Blin, Jens Nielsen, Bertrand Aigle, Amrita Pati, Harald Gross, Muriel Viaud, Pieter C. Dorrestein, Carla S. Jones, Michael A. Fischbach, Shelley M. Payne, Zhe Rui, Gerard D. Wright, Wen Liu, Alexey V. Melnik, Barry Scott, Brett A. Neilan, Nancy P. Keller, Rainer Borriss, Katrin Jungmann, Michalis Hadjithomas, Evi Stegmann, Daniel J. Edwards, F. Jerry Reen, Alexander Kristian Apel, Wolfgang Wohlleben, Michael J. Smanski, Leonard Katz, Fergal O'Gara, Eric J. N. Helfrich, Sergey B. Zotchev, Olivier Ploux, Arnold J. M. Driessen, Rolf Müller, Jean-Luc Pernodet, K. D. Entian, José A. Salas, Irene de Bruijn, Francisco Barona-Gómez, Jianhua Ju, Jon Clardy, Molecular Microbiology, Molecular Genetics, Jacobs University [Bremen], Microbial genomics and bioinformatics research group, Max Planck Institute for Marine Microbiology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Max-Planck-Gesellschaft, Atmospheric Chemistry Observations and Modeling Laboratory (ACOML), National Center for Atmospheric Research [Boulder] (NCAR), Department of Food and Environmental Sciences, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Collaborative Mass Spectrometry Innovation Center, University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Heilongjiang Institute of Science and Technology, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Merck Stiftungsprofessur fûr Molekulare Biotechnologie Fachbereich Biowissenscharten, Goethe-University Frankfurt am Main, Department of Opto-Mechatronics Engineering and Cogno-Mechatronics Engineering, Pusan National University, University of Liverpool, College of Computer Science and Technology [Zhejiang] (Zhejiang University), University of Florida [Gainesville] (UF), School of Management, University of Science and Technology of China [Hefei] (USTC), State Key Laboratory of Nuclear Physics and Technology (SKL-NPT), Peking University [Beijing], Massachusetts Institute of Technology (MIT), Memorial Sloane Kettering Cancer Center [New York], South China Sea Institute of Oceanology, Chinese Academy of Sciences [Beijing] (CAS), Dynamique des Génomes et Adaptation Microbienne (DynAMic), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Institut für Biologie [Berlin] (IFB), Humboldt University Of Berlin, School of Biomolecular and Biomedical Science and Centre for Synthesis and Chemical Biology, University College Dublin [Dublin] (UCD), Parallélisme, Réseaux, Systèmes, Modélisation (PRISM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pixyl Medical [Grenoble], Integrated Optical MicroSystems (IOMS), University of Twente-MESA+ Institute for Nanotechnology, 7Lehrstuhl für Mikrobielle Ökologie, Department für Grundlagen der Biowissenschaften, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service Néphrologie Pédiatrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Advanced Resources and Risk Technology, Laboratory of Phytopathology (K.C., H.S., B.A., M.H.), Universiteit Gent = Ghent University (UGENT), Trifork Aarhus C, Aalborg University [Denmark] (AAU), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Groupe d'Etude de la Matière Condensée (GEMAC), Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen [Groningen], DOE Joint Genome Institute [Walnut Creek], Microbiologie Moléculaire des Actinomycètes (ACTINO), Département Microbiologie (Dpt Microbio), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Gene Technology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Joint Center for Structural Genomics (JCSG), Stanford University, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches et d'Applications Pédagogiques en Langues (CRAPEL), Université Nancy 2, Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), Polytechnic Institute of Leiria, NMR Laboratory, Université de Mons, Université de Mons (UMons), School of Biomedical Science, Curtin University [Perth], Planning and Transport Research Centre (PATREC)-Planning and Transport Research Centre (PATREC), BIOMERIT Research Centre, School of Microbiology, University College Cork (UCC), Department of Engineering Science, University of Oxford, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Charles Friedel, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Phytopathology, Wageningen University and Research [Wageningen] (WUR), Department of Microbial Ecology, Netherlands Institute of Ecology, Department of Animal Production, Universidad de Córdoba = University of Córdoba [Córdoba], IMV Technologies, Gulliver (UMR 7083), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Institut für Chemie, Technical University of Berlin / Technische Universität Berlin (TU), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), DEPARTMENT OF CHEMISTRY, Durham University, Molekulare Ökologie, Joint Attosecond Science Laboratory, University of Ottawa and National Research Council, Department of Mechanical and Aerospace Engineering [Univ California Davis] (MAE - UC Davis), University of California [Davis] (UC Davis), University of Helsinki, University of California-University of California, Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Humboldt-Universität zu Berlin, University of Twente [Netherlands]-MESA+ Institute for Nanotechnology, Technische Universität München [München] (TUM), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Biosystems, KU Leuven, Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), University of California [Berkeley], NMR and Molecular Imaging Laboratory [Mons], University of Mons [Belgium] (UMONS), University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Universidad de Córdoba [Cordoba], Technische Universität Berlin (TU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Mechanical and Aerospace Engineering [Davis], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), University of Florida [Gainesville], Institut für Biologie, Humboldt Universität zu Berlin, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Ghent University [Belgium] (UGENT), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Stanford University [Stanford], Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), NMR and Molecular Imaging Laboratory, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS), Wageningen University and Research Centre [Wageningen] (WUR), Gulliver, ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Max Planck Society (GERMANY), Max Planck Society (GERMANY)-Max Planck Society (GERMANY), Laboratoire Leprince-Ringuet ( LLR ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Atmospheric Chemistry Observations and Modeling Laboratory ( ACOML ), National Center for Atmospheric Research [Boulder] ( NCAR ), University of California [San Diego] ( UC San Diego ), Eidgenössische Technische Hochschule [Zürich] ( ETH Zürich ), University of Science and Technology of China [Hefei] ( USTC ), State Key Laboratory of Nuclear Physics and Technology ( SKL-NPT ), Massachusetts Institute of Technology ( MIT ), Memorial Sloan Kettering Cancer Center ( MSKCC ), Shanghai Ocean University, Dynamique des Génomes et Adaptation Microbienne ( DynAMic ), Institut National de la Recherche Agronomique ( INRA ) -Université de Lorraine ( UL ), University College Dublin [Dublin] ( UCD ), Parallélisme, Réseaux, Systèmes, Modélisation ( PRISM ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Centre National de la Recherche Scientifique ( CNRS ), Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Integrated Optical MicroSystems ( IOMS ), Technische Universität München [München] ( TUM ), Ghent University [Belgium] ( UGENT ), Aalborg University [Denmark] ( AAU ), Centers for Disease Control and Prevention [Atlanta] ( CDC ), Groupe d'Etude de la Matière Condensée ( GEMAC ), Groningen Biomolecular Sciences and Biotechnology Institute ( GBB ), Microbiologie Moléculaire des Actinomycètes ( ACTINO ), Département Microbiologie ( Dpt Microbio ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique et microbiologie [Orsay] ( IGM ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Joint Center for Structural Genomics ( JCSG ), Centre européen de recherche et d'enseignement de géosciences de l'environnement ( CEREGE ), Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Collège de France ( CdF ) -Institut National de la Recherche Agronomique ( INRA ) -Institut national des sciences de l'Univers ( INSU - CNRS ), Centre de Recherches et d'Applications Pédagogiques en Langues ( CRAPEL ), Space Sciences Laboratory [Berkeley] ( SSL ), Université de Mons ( UMons ), Planning and Transport Research Centre ( PATREC ) -Planning and Transport Research Centre ( PATREC ), University College Cork ( UCC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ), Wageningen University and Research Centre [Wageningen] ( WUR ), ESPCI ParisTech, Technische Universität Berlin ( TUB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre de recherche Paul Pascal, CNRS, Université de Bordeaux ( UPR8641 ), Centre de Recherche Paul Pascal, CNRS, Université de Bordeaux, University Durham, University of California [Davis] ( UC Davis ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), and Saarland University, Building A4.1, 66123 Saarbruecken, Germany.

Subjects
MESH : Protein Biosynthesis, protein synthesis, Operon, MESH : Polysaccharides, International Cooperation, MESH: Plants, plant, Review, MESH: Terpenes, gene cluster, polyketide, data base, genetic database, Gene cluster, acyltransferase, Databases, Genetic, MESH : Metagenome, MESH : Genetic Markers, genetics, terpene, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), ComputingMilieux_MISCELLANEOUS, MESH : Peptides, MESH: Peptides, biology, fungus, nonribosomal peptide synthesis, Plants, bacterium, peptide, priority journal, MESH: Protein Biosynthesis, Multigene Family, MESH : Terpenes, MESH: Computational Biology, Genetic Markers, MESH: Terminology as Topic, Bioinformatics, MESH : Multigene Family, biological activity, Article, metagenome, Alkaloids, Manchester Institute of Biotechnology, Terminology as Topic, Bioinformatica, MESH : Bacteria, Peptide Biosynthesis, MESH : Databases, Genetic, Molecular Biology, MESH : Fungi, MESH: Polyketides, standardization, secondary metabolism, [ SDV ] Life Sciences [q-bio], Bacteria, ta1182, Computational Biology, MESH : Terminology as Topic, operon, Laboratorium voor Phytopathologie, MESH: International Cooperation, gene function, Metagenomics, polysaccharide, Laboratory of Phytopathology, chemical structure, Metagenome, MESH: Multigene Family, EPS, biosynthesis, Peptides, MESH : Computational Biology, MESH : International Cooperation, [SDV]Life Sciences [q-bio], MESH: Genetic Markers, information, MESH : Alkaloids, Synthetic biology, MESH: Peptide Biosynthesis, Nucleic Acid-Independent, database, MESH: Databases, Genetic, Genetics, MESH : Polyketides, MESH : Peptide Biosynthesis, Nucleic Acid-Independent, ddc:540, standards, Peptide Biosynthesis, Nucleic Acid-Independent, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, nomenclature, genetic marker, alkaloid derivative, MESH: Fungi, Biology, MESH : Plants, peptide derivative, Polyketide, MESH: Alkaloids, Polysaccharides, ddc:570, Life Science, 14. Life underwater, Secondary metabolism, enzyme specificity, Gene, nonhuman, Terpenes, Fungi, nucleotide sequence, Cell Biology, MESH: Metagenome, ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology, alkaloid, MESH: Bacteria, MESH: Polysaccharides, 13. Climate action, Polyketides, Protein Biosynthesis, synthetic biology, metabolism
Abstract

M.H.M. was supported by a Rubicon fellowship of the Netherlands Organization for Scientific Research (NWO;Rubicon 825.13.001). The work of R.K. was supported by the European Union’s Seventh Framework Programme(Joint Call OCEAN.2011–2: Marine microbial diversity—new insights into marine ecosystems functioning and its biotechnological potential) under the grant agreement no.287589 (Micro B3). M.C. was supported by a Biotechnology and Biological Sciences Research Council (BBSRC)studentship (BB/J014478/1). The GSC is supported by funding from the Natural Environment Research Council(UK), the National Institute for Energy Ethics and Society(NIEeS; UK), the Gordon and Betty Moore Foundation,the National Science Foundation (NSF; US) and the US Department of Energy. The Manchester Synthetic Biology Research Centre, SYNBIOCHEM, is supported by BBSRC/Engineering and Physical Sciences Research Council(EPSRC) grant BB/M017702/1, Medema, M.H., Kottmann, R., Yilmaz, P., Cummings, M., Biggins, J.B., Blin, K., De Bruijn, I., Chooi, Y.H., Claesen, J., Coates, R.C., Cruz-Morales, P., Duddela, S., Düsterhus, S., Edwards, D.J., Fewer, D.P., Garg, N., Geiger, C., Gomez-Escribano, J.P., Greule, A., Hadjithomas, M., Haines, A.S., Helfrich, E.J.N., Hillwig, M.L., Ishida, K., Jones, A.C., Jones, C.S., Jungmann, K., Kegler, C., Kim, H.U., Kötter, P., Krug, D., Masschelein, J., Melnik, A.V., Mantovani, S.M., Monroe, E.A., Moore, M., Moss, N., Nützmann, H.-W., Pan, G., Pati, A., Petras, D., Reen, F.J., Rosconi, F., Rui, Z., Tian, Z., Tobias, N.J., Tsunematsu, Y., Wiemann, P., Wyckoff, E., Yan, X., Yim, G., Yu, F., Xie, Y., Aigle, B., Apel, A.K., Balibar, C.J., Balskus, E.P., Barona-Gómez, F., Bechthold, A., Bode, H.B., Borriss, R., Brady, S.F., Brakhage, A.A., Caffrey, P., Cheng, Y.Q., Clardy, J., Cox, R.J., De Mot, R., Donadio, S., Donia, M.S., Van Der Donk, W.A., Dorrestein, P.C., Doyle, S., Driessen, A.J.M., Ehling-Schulz, M., Entian, K.-D., Fischbach, M.A., Gerwick, L., Gerwick, W.H., Gross, H., Gust, B., Hertweck, C., Höfte, M., Jensen, S.E., Ju, J., Katz, L., Kaysser, L., Klassen, J.L., Keller, N.P., Kormanec, J., Kuipers, O.P., Kuzuyama, T., Kyrpides, N.C., Kwon, H.-J., Lautru, S., Lavigne, R., Lee, C.Y., Linquan, B., Liu, X., Liu, W., Luzhetskyy, A., Mahmud, T., Mast, Y., Méndez, C., Metsä-Ketelä, M., Micklefield, J., Mitchell, D.A., Moore, B.S., Moreira, L.M., Müller, R., Neilan, B.A., Nett, M., Nielsen, J., O'Gara, F., Oikawa, H., Osbourn, A., Osburne, M.S., Ostash, B., Payne, S.M., Pernodet, J.-L., Petricek, M., Piel, J., Ploux, O., Raaijmakers, J.M., Salas, J.A., Schmitt, E.K., Scott, B., Seipke, R.F., Shen, B., Sherman, D.H., Sivonen, K., Smanski, M.J., Sosio, M., Stegmann, E., Süssmuth, R.D., Tahlan, K., Thomas, C.M., Tang, Y., Truman, A.W., Viaud, M., Walton, J.D., Walsh, C.T., Weber, T., Van Wezel, G.P., Wilkinson, B., Willey, J.M., Wohlleben, W., Wright, G.D., Ziemert, N., Zhang, C., Zotchev, S.B., Breitling, R., Takano, E., Glöckner, F.O.

Published
2015
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9. Implication of the melanocortin-3 receptor in the regulation of food intake

Author

Hossein Yarandi, Amanda M. Shaw, Jerry Ryan Holder, James B. Chambers, Deborah J. Clegg, William J. Millard, Zhimin Xiang, Marcus C. Moore, Carrie Haskell-Luevano, Rayna M. Bauzo, Boman G. Irani, Stephen C. Benoit, and Bettina Proneth

Subjects
medicine.medical_specialty, Molecular Sequence Data, Satiation, Biology, Ligands, Partial agonist, Article, Energy homeostasis, Eating, Gene Knockout Techniques, Mice, Melanocortin receptor, Internal medicine, medicine, Animals, Humans, Amino Acid Sequence, Pharmacology, digestive, oral, and skin physiology, Wild type, Melanocortin 3 receptor, Melanocortin 4 receptor, Endocrinology, alpha-MSH, Taste aversion, Receptor, Melanocortin, Type 4, Melanocortin, Oligopeptides, Receptor, Melanocortin, Type 3
Abstract

The melanocortin system is well recognized to be involved in the regulation of food intake, body weight, and energy homeostasis. To probe the role of the MC 3 in the regulation of food intake, JRH322-18 a mixed MC 3 partial agonist/antagonist and MC 4 agonist tetrapeptide was examined in wild type (WT) and melanocortin 4 receptor (MC 4 ) knockout mice and shown to reduce food intake in both models. In the wild type mice, 2.0 nmol of JRH322-18 statistically reduced food intake 4 h post icv treatment into satiated nocturnally feeding wild type mice. The same dose in the MC 4 KO mice significantly reduced cumulative food intake 24 h post treatment. Conditioned taste aversion as well as activity studies supports that the decreased food intake was not due to visceral illness. Since these studies resulted in loss-of-function results, the SHU9119 and agouti-related protein (AGRP) melanocortin receptor antagonists were administered to wild type as well as the MC 3 and MC 4 knockout mice in anticipation of gain-of-function results. The SHU9119 ligand produced an increase in food intake in the wild type mice as anticipated, however no effect was observed in the MC 3 and MC 4 knockout mice as compared to the saline control. The AGRP ligand however, produced a significant increase in food intake in the wild type as well as the MC 3 and MC 4 knockout mice and it had a prolonged affect for several days. These data support the hypothesis that the MC 3 plays a subtle role in the regulation of food intake, however the mechanism by which this is occurring remains to be determined.

Published
2011
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11. Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin‐4 receptor knockout mouse

Author

Amy Andreasen, Glenn A. Walter, Kim R. Haskell, Lorraine M. Koerper, William J. Millard, Sally A. Litherland, Henry V. Baker, Francois Rouzaud, Marcus C. Moore, Carrie Haskell-Luevano, Jay W. Schaub, and Zhimin Xiang

Subjects
Blood Glucose, Leptin, medicine.medical_specialty, Biochemistry, Research Communications, Mice, Proopiomelanocortin, Physical Conditioning, Animal, Internal medicine, Genetic model, Genetics, medicine, Hyperinsulinemia, Animals, Insulin, Obesity, RNA, Messenger, Pancreas, Molecular Biology, Mice, Knockout, biology, Body Weight, digestive, oral, and skin physiology, Organ Size, medicine.disease, Neuropeptide Y receptor, Magnetic Resonance Imaging, Orexin, Melanocortin 4 receptor, Cholesterol, Phenotype, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, Liver, Knockout mouse, biology.protein, Receptor, Melanocortin, Type 4, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, Biotechnology
Abstract

Exercise is a mechanism for maintenance of body weight in humans. Morbidly obese human patients have been shown to possess single nucleotide polymorphisms in the melanocortin-4 receptor (MC4R). MC4R knockout mice have been well characterized as a genetic model that possesses phenotypic metabolic disorders, including obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia, similar to those observed in humans possessing dysfunctional hMC4Rs. Using this model, we examined the effect of voluntary exercise of MC4R knockout mice that were allowed access to a running wheel for a duration of 8 wk. Physiological parameters that were measured included body weight, body composition of fat and lean mass, food consumption, body length, and blood levels of cholesterol and nonfasted glucose, insulin, and leptin. At the termination of the experiment, hypothalamic mRNA expression levels of neuropeptide Y (NPY), agouti-related protein (AGRP), proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), orexin, brain-derived neurotropic factor (BDNF), phosphatase with tensin homology (Pten), melanocortin-3 receptor (MC3R), and NPY-Y1R were determined. In addition, islet cell distribution and function in the pancreas were examined. In the exercising MC4R knockout mice, the pancreatic islet cell morphology and other physiological parameters resembled those observed in the wild-type littermate controls. Gene expression profiles identified exercise as having a significant effect on hypothalamic POMC, orexin, and MC3R levels. Genotype had a significant effect on AGRP, POMC, CART, and NPY-Y1R, with an exercise and genotype interaction effect on NPY gene expression. These data support the hypothesis that voluntary exercise can prevent the genetic predisposition of melanocortin-4 receptor-associated obesity and diabetes.—Haskell-Luevano, C., Schaub, J. W., Andreasen, A., Haskell, K. R., Moore, M. C., Koerper, L. M., Rouzaud, F., Baker, H. V., Millard, W. J., Walter, G., Litherland, S. A., Xiang, Z. Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin-4 receptor knockout mouse.

Published
2008
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12. Food motivated behavior of melanocortin-4 receptor knockout mice under a progressive ratio schedule

Author

C.H. Vaughan, Neil E. Rowland, Marcus C. Moore, and Carrie Haskell-Luevano

Subjects
Male, Heterozygote, medicine.medical_specialty, Schedule, Reinforcement Schedule, Physiology, Hyperphagia, Biochemistry, Eating, Mice, Cellular and Molecular Neuroscience, Endocrinology, Internal medicine, medicine, Animals, Mice, Knockout, Motivation, Meal, Behavior, Animal, Body Weight, Homozygote, digestive, oral, and skin physiology, Wild type, medicine.disease, Obesity, Circadian Rhythm, Melanocortin 4 receptor, Disease Models, Animal, Knockout mouse, Conditioning, Operant, Receptor, Melanocortin, Type 4, Conditioning, Progressive ratio, Psychology
Abstract

Melanocortin-4 receptor knockout (MC4RKO) mice are hyperphagic and develop obesity under free feeding conditions. We reported previously that MC4RKO mice did not maintain hyperphagia and as a result lost weight when required to press a lever to obtain food on a fixed ratio procurement schedule. To assess the generality of this result, we tested MC4RKO mice and their heterozygous and wild type littermates using progressive ratio (PR) schedules that are believed to be sensitive indicators of motivation. Mice lived in operant chambers and obtained all of their food (20 mg pellets) via lever press responding. Food was available according to a PR schedule so that within a meal, food became progressively more costly, and we expected this would provide a stringent test of mechanisms controlling meal size. The schedule reset after either 3 or 20 min of no responding, so defining meals, and the highest ratio completed before the reset was defined as the breakpoint. The average daily number of meals was lower and mean size of meals was higher at the 20 compared with the 3 min reset condition. Mean daily food intake did not differ between the two reset criteria but did differ as a function of genotype, with MC4RKO mice eating about 25% more than heterozygous or wild type mice. Hyperphagia in the MC4RKO mice was characterized primarily by larger meals (higher breakpoints) and they emitted about twice as many responses as wild type mice. Thus, using a PR schedule, MC4RKO mice exhibit hyperphagia, and show a high level of motivation to support large meal sizes.

Published
2006
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13. Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse

Author

Marcus C. Moore, Carrie Haskell-Luevano, Zhimin Xiang, Boman G. Irani, and Ronald J. Mandel

Subjects
medicine.medical_specialty, Litter Size, Biophysics, Hyperphagia, Biology, Biochemistry, Energy homeostasis, Mice, Physical Conditioning, Animal, Internal medicine, medicine, Animals, Obesity, Receptor, Molecular Biology, Mice, Knockout, Leptin, Age Factors, Cell Biology, medicine.disease, Phenotype, Melanocortin 4 receptor, Endocrinology, Knockout mouse, Receptor, Melanocortin, Type 4, Melanocortin
Abstract

The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight = 31 ± 1.8 g versus conventionally housed body weight = 41 ± 2.3 g, a 25% decrease in body weight p

Published
2005
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15. Tetanus seropositive prevalence and perceived protection from emergency admissions

Author

Todd Britt, Kimberly R. Barber, and Marcus A. Moore

Subjects
Pediatrics, medicine.medical_specialty, emergency department, Epidemiology, Health, Toxicology and Mutagenesis, Single Center, immunization, complex mixtures, 03 medical and health sciences, 0302 clinical medicine, medicine, Medical history, Tetanus, business.industry, Health Policy, Tetanus, immunization, vaccination, patient history, Emergency Department, Public Health, Environmental and Occupational Health, Primary care physician, Antibody titer, 030208 emergency & critical care medicine, General Medicine, Emergency department, medicine.disease, vaccination, Vaccination, Immunization, patient history, Original Article, business
Abstract

Background: Emergency physicians see many people who present to the emergency department stating that they are immunized against tetanus, when in fact, they are not. The patient history is not dependable for determining true tetanus status and simple patient surveys do not provide actual prevalence. The objective of this study was to determine the prevalence of tetanus status by antibody titer seropositivity and quantify such status among patients reporting tetanus protection. Methods: This study is a single center prospective convenience sample of patients presenting to the emergency department 12 years of age or older. Patients deemed study candidates and willing to be in the study filled out an eight-question questionnaire that included the question ‘is your tetanus shot up to date’. A blood sample was then drawn for tetanus antibody titer and quantified according to a pre-determined cutoff for protection. Results: A total of 163 patients were enrolled. Of patients responding yes to the query ‘is your tetanus shot up to date’ 12.8% (N=5) of them were not seropositive. Of the 26 people who were seronegative in the study all had been to a doctor in the past year and 88.5% (N=23) had been to their family physician. Conclusion: The study suggests that it may be difficult to trust the tetanus immunization history given by patients presenting to the emergency room. The study also observed that a large percentage of patients who were serenegative were seen by a primary care physician and not had a necessary tetanus immunization. Keywords: Tetanus; immunization; vaccination; patient history; emergency department (Published: 9 February 2012) Citation: Emerg Health Threats J 2012, 5 : 7718 - DOI: 10.3402/ehtj.v5i0.7718

Published
2012

16. Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice

Author

Boman G. Irani, William J. Millard, Marcus C. Moore, Carrie Haskell-Luevano, and Amanda M. Shaw

Subjects
Male, medicine.medical_specialty, Physiology, Biology, Biochemistry, Cellular and Molecular Neuroscience, Eating, Mice, Endocrinology, Melanocortin receptor, Internal medicine, Orexigenic, medicine, Animals, Humans, Mice, Knockout, digestive, oral, and skin physiology, Neuropeptide Y receptor, Growth hormone secretion, Ghrelin, Rats, Growth Hormone, Knockout mouse, Receptor, Melanocortin, Type 4, Female, Melanocortin, Agouti-related peptide, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Receptor, Melanocortin, Type 3
Abstract

Ghrelin stimulates food intake in part by activating hypothalamic neuropeptide Y (NPY) neurons/agouti related peptide (AGRP) neurons. We investigated the role of AGRP/melanocortin signaling in ghrelin-induced food intake by studying melanocortin 3 and 4 receptor knockout (MC3R KO and MC4R KO) mice. We also determined whether reduced ghrelin levels and/or an altered sensitivity to the GH-stimulating effects of ghrelin accompany the obesity syndromes of MC3R KO and MC4R KO mice. Compared to wild-type (WT) mice, the effects of ghrelin on food intake were reduced in MC3R KO and MC4R KO mice and circulating ghrelin levels were reduced in female MC4R KO mice. Female MC3R KO and MC4R KO mice exhibited a diminished responsiveness to the GH-releasing effects of ghrelin. Thus, deletion of the MC3R or MC4R results in a decreased sensitivity to ghrelin and verifies the involvement in the melanocortin system in ghrelin-induced food intake.

Published
2004

17. Meal patterns and foraging in melanocortin receptor knockout mice

Author

Neil E. Rowland, Marcus C. Moore, Carrie Haskell-Luevano, and C.H. Vaughan

Subjects
Male, medicine.medical_specialty, business.product_category, Reinforcement Schedule, Foraging, Experimental and Cognitive Psychology, Biology, Behavioral Neuroscience, Mice, Melanocortin receptor, Internal medicine, medicine, Animals, Receptor, Mice, Knockout, Lever, Meal, Analysis of Variance, Behavior, Animal, digestive, oral, and skin physiology, Wild type, Feeding Behavior, Endocrinology, Knockout mouse, Conditioning, Operant, Receptor, Melanocortin, Type 4, Melanocortin, business, Receptor, Melanocortin, Type 3
Abstract

We report the meal patterns of mice with the deletion of either the melanocortin type 3 or 4 receptors (MC3RKO or MC4RKO) compared with that of the wild type (WT) under conditions of varying foraging costs. Mice lived in two-lever operant chambers; the completion of a designated number of responses (termed procurement fixed ratio or PFR) on the "foraging" lever activated the other lever. On this second lever, the completion of a designated number of responses (termed consumatory fixed ratio or CFR) caused the delivery of a 20-mg food pellet. Animals could complete as many CFRs as they wished to constitute a meal, but whenever 10 min elapsed without pressing on this second lever, the meal was terminated and pressing on the "foraging" lever was again required to initiate a new meal. At lower PFRs, mice of all three genotypes took 5-7 well-defined meals per day of approximately 35 pellets/meal. At the highest PFR, mice of all three groups took about half this number of meals, with some increase in meal size, and total intake was slightly reduced. MC4RKO mice were obese compared with WT or MC3RKO but failed to eat more food in the operant chambers and, as a consequence, lost weight, regardless of PFR. Thus, changes in meal-taking strategies as a function of imposed foraging cost are not critically dependent on either MC3 or MC4 receptors, but these conditions did not allow us to study meal patterns in MC4RKO mice that are hyperphagic.

Published
2004

18. Familial Ebstein's anomaly of the tricuspid valve

Author

Marcus M. Moore, J. Russell Green, Francisco A. Hernandez, Thomas M. Wiley, Gerold L. Schiebler, and Charles C. Donegan

Subjects
Adult, Male, medicine.medical_specialty, Heart disease, medicine.medical_treatment, Vectorcardiography, Internal medicine, Ebstein's anomaly, medicine, Humans, cardiovascular diseases, Child, Cardiac catheterization, Atrioventricular valve, Tricuspid valve, business.industry, medicine.disease, Ebstein Anomaly, Radiography, medicine.anatomical_structure, Congenitally corrected transposition, Great vessels, cardiovascular system, Cardiology, Maternal Uncle, Cardiology and Cardiovascular Medicine, business
Abstract

Ebstein's anomaly of the tricuspid valve has not been reported previously in two members of the same family. A 6-year-old boy and his 29-year-old maternal uncle are described, both of whom had the Ebstein type of tricuspid valve documented by cardiac catheterization. A review of the literature suggests that when multiple cases of congenital heart disease occur in a family in which one individual has Ebstein's malformation of the tricuspid valve, another member may have the same anomaly; or even more likely, an analagous anomaly of the left-sided atrioventricular valve with or without congenitally corrected transposition of the great vessels.

Published
1968
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