Confirmation of Pathogenic Mechanisms by SARS-Cov-2–Host
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Dehydrogenase Gene of Entamoeba Histolytica
Proc. Nad. Acad. Sci. USA Vol. 89, pp. 10188-10192, November 1992 Medical Sciences Cloning and expression of an NADP+-dependent alcohol dehydrogenase gene of Entamoeba histolytica (amebiasis/protozoan parasite/fermentation/inhibitors) AJIT KUMAR*, PEI-SHEN SHENtt, STEVEN DESCOTEAUX*, JAN POHL§, GORDON BAILEYt, AND JOHN SAMUELSON*1II *Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115; tDepartment of Biochemistry, Morehouse School of Medicine, Atlanta, GA 30310; §Microchemical Facility, Emory University, Atlanta, GA 30322; and 'Department of Pathology, New England Deaconess Hospital, Boston, MA 02215 Communicated by Elkan Blout, June 29, 1992 (receivedfor review May 1, 1992) ABSTRACT Ethanol is the major metabolic product of NAD(P)+ so that the reducing equivalents are regenerated glucose fermentation by the protozoan parasite Entmoeba (4-7). Both NADP+-dependent and NAD+-dependent alco- histolytica under the anaerobic conditions found in the lumen hol dehydrogenase (ADH) activities have been identified in of the colon. Here an internal peptide sequence determined E. histolytica trophozoites (4-7). The NADP+-dependent from a major 39-kDa amoeba protein isolated by isoeLtric ADH (EhADHi; EC 1.1.1.2) was found to be composed of focusing followed by SDS/PAGE was used to clone the gene for four -30-kDa subunits, prefer secondary alcohols to primary the E. histolytica NADP+-dependent alcohol dehydrogenase alcohols, and be inhibited by the substrate analogue pyrazole (EhADH1; EC 1.1.1.2). The EhADHi clone had an open (7). The amoeba NAD+-dependent ADH (EC 1.1.1.1) is not reading frame that was 360 amino acids long and encoded a well-characterized (4). -
Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice
Loyola University Chicago Loyola eCommons Biology: Faculty Publications and Other Works Faculty Publications 2013 Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice Mihaela Palicev Gunter P. Wagner James P. Noonan Benedikt Hallgrimsson James M. Cheverud Loyola University Chicago, [email protected] Follow this and additional works at: https://ecommons.luc.edu/biology_facpubs Part of the Biology Commons Recommended Citation Palicev, M, GP Wagner, JP Noonan, B Hallgrimsson, and JM Cheverud. "Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice." Genome Biology and Evolution 5(10), 2013. This Article is brought to you for free and open access by the Faculty Publications at Loyola eCommons. It has been accepted for inclusion in Biology: Faculty Publications and Other Works by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. © Palicev et al., 2013. GBE Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice Mihaela Pavlicev1,2,*, Gu¨ nter P. Wagner3, James P. Noonan4, Benedikt Hallgrı´msson5,and James M. Cheverud6 1Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria 2Department of Pediatrics, Cincinnati Children‘s Hospital Medical Center, Cincinnati, Ohio 3Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University 4Department of Genetics, Yale University School of Medicine 5Department of Cell Biology and Anatomy, The McCaig Institute for Bone and Joint Health and the Alberta Children’s Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Canada 6Department of Anatomy and Neurobiology, Washington University *Corresponding author: E-mail: [email protected]. -
Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins. -
The Failure of Two Major Formaldehyde Catabolism Enzymes (ADH5 and ALDH2) Leads to Partial Synthetic Lethality in C57BL/ 6 Mice Jun Nakamura1,2*, Darcy W
Nakamura et al. Genes and Environment (2020) 42:21 https://doi.org/10.1186/s41021-020-00160-4 SHORT REPORT Open Access The failure of two major formaldehyde catabolism enzymes (ADH5 and ALDH2) leads to partial synthetic lethality in C57BL/ 6 mice Jun Nakamura1,2*, Darcy W. Holley3, Toshihiro Kawamoto4 and Scott J. Bultman3 Abstract Background: Exogenous formaldehyde is classified by the IARC as a Category 1 known human carcinogen. Meanwhile, a significant amount of endogenous formaldehyde is produced in the human body; as such, formaldehyde-derived DNA and protein adducts have been detected in animals and humans in the absence of major exogenous formaldehyde exposure. However, the toxicological effects of endogenous formaldehyde on individuals with normal DNA damage repair functions are not well understood. In this study, we attempted to generate C57BL/6 mice deficient in both Adh5 and Aldh2, which encode two major enzymes that metabolize endogenous formaldehyde, in order to understand the effects of endogenous formaldehyde on mice with normal DNA repair function. Results: Due to deficiencies in both ADH5 and ALDH2, few mice survived past post-natal day 21. In fact, the survival of pups within the first few days after birth was significantly decreased. Remarkably, two Aldh2−/−/Adh5−/− mice survived for 25 days after birth, and we measured their total body weight and organ weights. The body weight of Aldh2−/−/Adh5−/− mice decreased significantly by almost 37% compared to the Aldh2−/−/Adh5+/− and Aldh2−/−/Adh5+/+ mice of the same litter. In addition, the absolute weight of each organ was also significantly reduced. Conclusion: Mice deficient in both formaldehyde-metabolizing enzymes ADH5 and ALDH2 were found to develop partial synthetic lethality and mortality shortly after birth. -
Plasma Kallikrein Activation and Inhibition During Typhoid Fever
Plasma Kallikrein Activation and Inhibition during Typhoid Fever Robert W. Colman, … , Cheryl F. Scott, Robert H. Gilman J Clin Invest. 1978;61(2):287-296. https://doi.org/10.1172/JCI108938. Research Article As an ancillary part of a typhoid fever vaccine study, 10 healthy adult male volunteers (nonimmunized controls) were serially bled 6 days before to 30 days after ingesting 105Salmonella typhi organisms. Five persons developed typhoid fever 6-10 days after challenge, while five remained well. During the febrile illness, significant changes (P < 0.05) in the following hematological parameters were measured: a rise in α1-antitrypsin antigen concentration and high molecular weight kininogen clotting activity; a progressive decrease of platelet count (to 60% of the predisease state), functional prekallikrein (55%) and kallikrein inhibitor (47%) with a nadir reached on day 5 of the fever and a subsequent overshoot during convalescence. Despite the drop in functional prekallikrein and kallikrein inhibitor, there was no change in factor XII clotting activity or antigenic concentrations of prekallikrein and the kallikrein inhibitors, C1 esterase inhibitor (C1-̄ INH) and α2-macroglobulin. Plasma from febrile patients subjected to immunoelectrophoresis and crossed immunoelectrophoresis contained a new complex displaying antigenic characteristics of both prekallikrein and C1-̄ INH; the α2-macroglobulin, antithrombin III, and α1-antitrypsin immunoprecipitates were unchanged. Plasma drawn from infected-well subjects showed no significant change in these components of the kinin generating system. The finding of a reduction in functional prekallikrein and kallikrein inhibitor (C1-̄ INH) and the formation of a kallikrein C1-̄ INH complex is consistent with prekallikrein activation in typhoid fever. -
Hemoglobin Interaction with Gp1ba Induces Platelet Activation And
ARTICLE Platelet Biology & its Disorders Hemoglobin interaction with GP1bα induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis Rashi Singhal,1,2,* Gowtham K. Annarapu,1,2,* Ankita Pandey,1 Sheetal Chawla,1 Amrita Ojha,1 Avinash Gupta,1 Miguel A. Cruz,3 Tulika Seth4 and Prasenjit Guchhait1 1Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region, Biotech Science Cluster, Faridabad, India; 2Biotechnology Department, Manipal University, Manipal, Karnataka, India; 3Thrombosis Research Division, Baylor College of Medicine, Houston, TX, USA, and 4Hematology, All India Institute of Medical Sciences, New Delhi, India *RS and GKA contributed equally to this work. ABSTRACT Intravascular hemolysis increases the risk of hypercoagulation and thrombosis in hemolytic disorders. Our study shows a novel mechanism by which extracellular hemoglobin directly affects platelet activation. The binding of Hb to glycoprotein1bα activates platelets. Lower concentrations of Hb (0.37-3 mM) significantly increase the phos- phorylation of signaling adapter proteins, such as Lyn, PI3K, AKT, and ERK, and promote platelet aggregation in vitro. Higher concentrations of Hb (3-6 mM) activate the pro-apoptotic proteins Bak, Bax, cytochrome c, caspase-9 and caspase-3, and increase platelet clot formation. Increased plasma Hb activates platelets and promotes their apoptosis, and plays a crucial role in the pathogenesis of aggregation and development of the procoagulant state in hemolytic disorders. Furthermore, we show that in patients with paroxysmal nocturnal hemoglobinuria, a chronic hemolytic disease characterized by recurrent events of intravascular thrombosis and thromboembolism, it is the elevated plasma Hb or platelet surface bound Hb that positively correlates with platelet activation. -
New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology
Cancer Research and Treatment 2003;35(4):304-313 New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology Yong-Wan Kim, Ph.D.1, Min-Je Suh, M.S.1, Jin-Sik Bae, M.S.1, Su Mi Bae, M.S.1, Joo Hee Yoon, M.D.2, Soo Young Hur, M.D.2, Jae Hoon Kim, M.D.2, Duck Young Ro, M.D.2, Joon Mo Lee, M.D.2, Sung Eun Namkoong, M.D.2, Chong Kook Kim, Ph.D.3 and Woong Shick Ahn, M.D.2 1Catholic Research Institutes of Medical Science, 2Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul; 3College of Pharmacy, Seoul National University, Seoul, Korea Purpose: This study utilized both mRNA differential significant genes of unknown function affected by the display and the Gene Ontology (GO) analysis to char- HPV-16-derived pathway. The GO analysis suggested that acterize the multiple interactions of a number of genes the cervical cancer cells underwent repression of the with gene expression profiles involved in the HPV-16- cancer-specific cell adhesive properties. Also, genes induced cervical carcinogenesis. belonging to DNA metabolism, such as DNA repair and Materials and Methods: mRNA differential displays, replication, were strongly down-regulated, whereas sig- with HPV-16 positive cervical cancer cell line (SiHa), and nificant increases were shown in the protein degradation normal human keratinocyte cell line (HaCaT) as a con- and synthesis. trol, were used. Each human gene has several biological Conclusion: The GO analysis can overcome the com- functions in the Gene Ontology; therefore, several func- plexity of the gene expression profile of the HPV-16- tions of each gene were chosen to establish a powerful associated pathway, identify several cancer-specific cel- cervical carcinogenesis pathway. -
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. -
Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development
International Journal of Molecular Sciences Review Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development Charles Ducker * and Peter E. Shaw * Queen’s Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK * Correspondence: [email protected] (C.D.); [email protected] (P.E.S.) Abstract: Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers. Keywords: E3 ligase complex; deubiquitinase; gene fusions; mitogens; phosphorylation; DNA damage 1. Introduction Citation: Ducker, C.; Shaw, P.E. Cell growth, proliferation and differentiation are complex, concerted processes that Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer rely on careful regulation of gene expression. Control over gene expression is maintained and Development. Int. J. Mol. Sci. through signalling pathways that respond to external cellular stimuli, such as growth 2021, 22, 5119. https://doi.org/ factors, cytokines and chemokines, that invoke expression profiles commensurate with 10.3390/ijms22105119 diverse cellular outcomes. -
Age-Dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver S
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2017/08/21/dmd.117.076463.DC2 http://dmd.aspetjournals.org/content/suppl/2017/06/12/dmd.117.076463.DC1 1521-009X/45/9/1044–1048$25.00 https://doi.org/10.1124/dmd.117.076463 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 45:1044–1048, September 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics Age-dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver s Deepak Kumar Bhatt, Andrea Gaedigk, Robin E. Pearce, J. Steven Leeder, and Bhagwat Prasad Department of Pharmaceutics, University of Washington, Seattle, Washington (D.K.B., B.P.); Department of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy-Kansas City, Missouri and School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri (A.G., R.E.P., J.S.L.) Received April 21, 2017; accepted June 5, 2017 ABSTRACT Hepatic cytosolic alcohol and aldehyde dehydrogenases (ADHs and the adult levels, respectively. For all proteins, the abundance steeply ALDHs) catalyze the biotransformation of xenobiotics (e.g., cyclo- increased during the first year of life, which mostly reached adult Downloaded from phosphamide and ethanol) and vitamin A. Because age-dependent levels during early childhood (age between 1 and 6 years). Only for hepatic abundance of these proteins is unknown, we quantified ADH1A protein abundance in adults (age > 18 year) was ∼40% lower protein expression of ADHs and ALDH1A1 in a large cohort of pediatric relative to the early childhood group. Abundances of ADHs and and adult human livers by liquid chromatography coupled with tandem ALDH1A1 were not associated with sex in samples with age > 1 year mass spectrometry proteomics. -
Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces Cerevisiae
Metabolites 2013, 3, 1102-1117; doi:10.3390/metabo3041102 OPEN ACCESS metabolites ISSN 2218-1989 www.mdpi.com/journal/metabolites/ Article Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae Stefan Jenkins 1,2,3,*, Steven M. Fischer 2, Lily Chen 3 and Theodore R. Sana 2 1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA 2 Agilent Technologies, Life Sciences, Diagnostics and Applied Markets, Santa Clara, CA 95051, USA; E-Mails: [email protected] (S.M.F.); [email protected] (T.R.S.) 3 Biology Department, San Francisco State University, San Francisco, CA 94132, USA; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-650-922-5046; Fax: +1-510-486-4545. Received: 15 October 2013; in revised form: 20 November 2013 / Accepted: 25 November 2013 / Published: 6 December 2013 Abstract: Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP) and aqueous normal phase (ANP) chromatographic separations, as well as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources for detection in both ion polarities. -
And Macro-Level Network Metrics Unveils Top Communicative Gene Modules in Psoriasis
G C A T T A C G G C A T genes Article Using Micro- and Macro-Level Network Metrics Unveils Top Communicative Gene Modules in Psoriasis 1, 2 3 Reyhaneh Naderi y, Homa Saadati Mollaei , Arne Elofsson 3, , and Saman Hosseini Ashtiani * y 1 Department of Artificial Intelligence and Robotics, Faculty of Computer Engineering, Iran University of Science and Technology, Tehran 1684613114, Iran; [email protected] 2 Department of Advanced Sciences and Technology, Islamic Azad University Tehran Medical Sciences, Tehran 1916893813, Iran; [email protected] 3 Department of Biochemistry and Biophysics and Science for Life Laboratory, Stockholm University, 106 91 Stockholm, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-762623644 These authors contributed equally to this work and should be considered joint first authors. y Received: 9 July 2020; Accepted: 6 August 2020; Published: 10 August 2020 Abstract: (1) Background: Psoriasis is a multifactorial chronic inflammatory disorder of the skin, with significant morbidity, characterized by hyperproliferation of the epidermis. Even though psoriasis’ etiology is not fully understood, it is believed to be multifactorial, with numerous key components. (2) Methods: In order to cast light on the complex molecular interactions in psoriasis vulgaris at both protein–protein interactions and transcriptomics levels, we studied a set of microarray gene expression analyses consisting of 170 paired lesional and non-lesional samples. Afterwards, a network analysis was conducted on the protein–protein interaction network of differentially expressed genes based on micro- and macro-level network metrics at a systemic level standpoint. (3) Results: We found 17 top communicative genes, all of which were experimentally proven to be pivotal in psoriasis, which were identified in two modules, namely the cell cycle and immune system.