Modifiers of Beta-Amyloid Metabolism and Deposition in Mouse Models of Alzheimer’S Disease
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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). -
Genome-Wide Association Study of Increasing Suicidal Ideation During Antidepressant Treatment in the GENDEP Project
The Pharmacogenomics Journal (2012) 12, 68–77 & 2012 Macmillan Publishers Limited. All rights reserved 1470-269X/12 www.nature.com/tpj ORIGINAL ARTICLE Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project NPerroud1,2,3,RUher1, Suicidal thoughts during antidepressant treatment have been the focus of 1 2,3,4 several candidate gene association studies. The aim of the present genome- MYM Ng , M Guipponi , wide association study was to identify additional genetic variants involved in 5 6 JHauser, N Henigsberg , increasing suicidal ideation during escitalopram and nortriptyline treatment. WMaier7,OMors8, A total of 706 adult participants of European ancestry, treated for major M Gennarelli9, M Rietschel10, depression with escitalopram or nortriptyline over 12 weeks in the Genome- DSouery11, MZ Dernovsek12, Based Therapeutic Drugs for Depression (GENDEP) study were genotyped 13 14 with Illumina Human 610-Quad Beadchips (Illumina, San Diego, CA, USA). AS Stamp ,MLathrop , A total of 244 subjects experienced an increase in suicidal ideation AFarmer1, G Breen1,KJAitchison1, during follow-up. The genetic marker most significantly associated with CM Lewis1,IWCraig1 increasing suicidality (8.28 Â 10À7) was a single-nucleotide polymorphism and P McGuffin1 (SNP; rs11143230) located 30 kb downstream of a gene encoding guanine deaminase (GDA) on chromosome 9q21.13. Two suggestive drug-specific 1MRC Social, Genetic and Developmental Psychiatry associations within KCNIP4 (Kv channel-interacting protein 4; chromosome Centre, Institute of Psychiatry, King’s College 4p15.31) and near ELP3 (elongation protein 3 homolog; chromosome London, London, UK; 2Department of Psychiatry, 8p21.1) were found in subjects treated with escitalopram. -
Identification of the Binding Partners for Hspb2 and Cryab Reveals
Brigham Young University BYU ScholarsArchive Theses and Dissertations 2013-12-12 Identification of the Binding arP tners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non- Redundant Roles for Small Heat Shock Proteins Kelsey Murphey Langston Brigham Young University - Provo Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Microbiology Commons BYU ScholarsArchive Citation Langston, Kelsey Murphey, "Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins" (2013). Theses and Dissertations. 3822. https://scholarsarchive.byu.edu/etd/3822 This Thesis is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston A thesis submitted to the faculty of Brigham Young University in partial fulfillment of the requirements for the degree of Master of Science Julianne H. Grose, Chair William R. McCleary Brian Poole Department of Microbiology and Molecular Biology Brigham Young University December 2013 Copyright © 2013 Kelsey Langston All Rights Reserved ABSTRACT Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactors and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston Department of Microbiology and Molecular Biology, BYU Master of Science Small Heat Shock Proteins (sHSP) are molecular chaperones that play protective roles in cell survival and have been shown to possess chaperone activity. -
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. -
AKAP8L Rabbit Polyclonal Antibody – TA329433 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA329433 AKAP8L Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: WB Recommended Dilution: WB Reactivity: Human Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: The immunogen for Anti-AKAP8L antibody is: synthetic peptide directed towards the C- terminal region of Human AKAP8L. Synthetic peptide located within the following region: NNKLISKKLERYLKGENPFTDSPEEEKEQEEAEGGALDEGAQGEAAGISE Formulation: Liquid. Purified antibody supplied in 1x PBS buffer with 0.09% (w/v) sodium azide and 2% sucrose. Note that this product is shipped as lyophilized powder to China customers. Purification: Affinity Purified Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 64 kDa Gene Name: A-kinase anchoring protein 8 like Database Link: NP_055186 Entrez Gene 26993 Human Q9ULX6 Background: AKAP8L could play a role in constitutive transport element (CTE)-mediated gene expression. It does not seem to be implicated in the binding of regulatory subunit II of PKA. It may be involved in nuclear envelope breakdown and chromatin condensation. It may regulate the initiation phase of DNA replication when associated with TMPO-beta. Synonyms: HA95; HAP95; NAKAP; NAKAP95 This product is to be used for laboratory only. Not for diagnostic -
Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance Through Cu2+-Binding
Biomolecules 2014, 4, 510-526; doi:10.3390/biom4020510 OPEN ACCESS biomolecules ISSN 2218-273X www.mdpi.com/journal/biomolecules/ Article Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance through Cu2+-Binding Aya Kojima 1,2, Motomi Konishi 1 and Toshifumi Akizawa 1,* 1 Analytical Chemistry, Pharmaceutical Science, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan; E-Mails: [email protected] (A.K.); [email protected] (M.K.) 2 Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 180-8639, Japan * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel./Fax: +81-72-866-3129. Received: 31 January 2014; in revised form: 2 April 2014 / Accepted: 11 April 2014 / Published: 8 May 2014 Abstract: Prions are the cause of neurodegenerative disease in humans and other mammals. The structural conversion of the prion protein (PrP) from a normal cellular protein (PrPC) to a protease-resistant isoform (PrPSc) is thought to relate to Cu2+ binding to histidine residues. In this study, we focused on the membrane-type matrix metalloproteinases (MT-MMPs) such as MT1-MMP and MT3-MMP, which are expressed in the brain as PrPC-degrading proteases. We synthesized 21 prion fragment peptides. Each purified peptide was individually incubated with recombinant MT1-MMP or MT3-MMP in the presence or absence of Cu2+ and the cleavage sites determined by LC-ESI-MS analysis. Recombinant MMP-7 and human serum (HS) were also tested as control. -
Use of Genomic Tools to Discover the Cause of Champagne Dilution Coat Color in Horses and to Map the Genetic Cause of Extreme Lordosis in American Saddlebred Horses
University of Kentucky UKnowledge Theses and Dissertations--Veterinary Science Veterinary Science 2014 USE OF GENOMIC TOOLS TO DISCOVER THE CAUSE OF CHAMPAGNE DILUTION COAT COLOR IN HORSES AND TO MAP THE GENETIC CAUSE OF EXTREME LORDOSIS IN AMERICAN SADDLEBRED HORSES Deborah G. Cook University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cook, Deborah G., "USE OF GENOMIC TOOLS TO DISCOVER THE CAUSE OF CHAMPAGNE DILUTION COAT COLOR IN HORSES AND TO MAP THE GENETIC CAUSE OF EXTREME LORDOSIS IN AMERICAN SADDLEBRED HORSES" (2014). Theses and Dissertations--Veterinary Science. 15. https://uknowledge.uky.edu/gluck_etds/15 This Doctoral Dissertation is brought to you for free and open access by the Veterinary Science at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Veterinary Science by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. -
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. -
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. -
ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease
International Journal of Molecular Sciences Review ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease Francesca Tosetti 1,* , Massimo Alessio 2, Alessandro Poggi 1,† and Maria Raffaella Zocchi 3,† 1 Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico S. Martino Largo R. Benzi 10, 16132 Genoa, Italy; [email protected] 2 Proteome Biochemistry, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; [email protected] 3 Division of Immunology, Transplants and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work as last author. Abstract: Enzymes, once considered static molecular machines acting in defined spatial patterns and sites of action, move to different intra- and extracellular locations, changing their function. This topological regulation revealed a close cross-talk between proteases and signaling events involving post-translational modifications, membrane tyrosine kinase receptors and G-protein coupled recep- tors, motor proteins shuttling cargos in intracellular vesicles, and small-molecule messengers. Here, we highlight recent advances in our knowledge of regulation and function of A Disintegrin And Metalloproteinase (ADAM) endopeptidases at specific subcellular sites, or in multimolecular com- plexes, with a special focus on ADAM10, and tumor necrosis factor-α convertase (TACE/ADAM17), since these two enzymes belong to the same family, share selected substrates and bioactivity. We will discuss some examples of ADAM10 activity modulated by changing partners and subcellular compartmentalization, with the underlying hypothesis that restraining protease activity by spatial Citation: Tosetti, F.; Alessio, M.; segregation is a complex and powerful regulatory tool. -
Using Evolutionary Conserved Modules in Gene Networks As a Strategy to Leverage High Throughput Gene Expression Queries Jeanne M
Ecology, Evolution and Organismal Biology Ecology, Evolution and Organismal Biology Publications 9-2010 Using Evolutionary Conserved Modules in Gene Networks as a Strategy to Leverage High Throughput Gene Expression Queries Jeanne M. Serb Iowa State University, [email protected] Megan C. Orr Iowa State University M. Heather West Greenlee Iowa State University, [email protected] Follow this and additional works at: http://lib.dr.iastate.edu/eeob_ag_pubs Part of the Ecology and Evolutionary Biology Commons, Genetics Commons, and the Systems Biology Commons The ompc lete bibliographic information for this item can be found at http://lib.dr.iastate.edu/ eeob_ag_pubs/19. For information on how to cite this item, please visit http://lib.dr.iastate.edu/ howtocite.html. This Article is brought to you for free and open access by the Ecology, Evolution and Organismal Biology at Iowa State University Digital Repository. It has been accepted for inclusion in Ecology, Evolution and Organismal Biology Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Using Evolutionary Conserved Modules in Gene Networks as a Strategy to Leverage High Throughput Gene Expression Queries Abstract Background: Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seednetwork of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. -
1) (As of December 2018) and the Latest GWAS of AD (2
SUPPLEMENTARY FIGURES downstream intergenic ncRNA_exonic upstream ●936 ●918 group downstream intergenic ncRNA_exonic upstream group exonic exonicintronicintronic ncRNA_intronic ncRNA_intronicUTR3 UTR3 3.8% 1.2%1.5%1.9% 3.8% 5.4%5.4% 750 0.3% 3.8%1.2%1.5%1.9% ●700 5.4% ●670 0.3% 500 45.8% 40.240.2% % 45.8% ●329 ●274 250 ●223 Number (GWAS SNPs/studies) Number (GWAS ●128 ●105 45.8% ●54 ●57 ●58 ●48 ●42 ●46 ●50 ●30 ●3740.2% ● ●17 ●25 ●4 ●6 ●12 0 ● 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Year Supplementary Figure S1. GWAS of AD since 2007. The figure is based on data from the GWAS Catalog (1) (as of December 2018) and the latest GWAS of AD (2). The green area shows the total number of AD-associated SNPs, and the purple area shows the total number of GWAS of AD. The insert chart shows the proportions of different types of all 936 AD-associated SNPs. 1 100 200 RPS27A TGFB2 BIN1 C4BPB MSH2 PROC UGT1A1 RAB1A TTN DISC1 50 PDCL3 COL4A3 CD55 ERCC3 100 USP21 C4BPA ITSN2 PTPRF MPZ FMN2 INPP5D CEP85 FNBP1L CSF1 CD46 ADAMTS4 PRKRA SPRED2 0 CTNNA2 DGKD ADCY10 ZAP70 LIMS2 PDE1A PROX1 0 CHRNB2 CR1 HSPG2 SH3BGRL3 DAB1 CTBS FCER1G MAP3K2 AD risk score or log10(P value) IL6R CDC73 CD34 AD risk score or log10(P value) −50 B4GALT3 IL19 0 50 100 150 200 250 0 50 100 150 200 Chromosome 1 (Mb) Chromosome 2 (Mb) ATP2B2 LTF ARF4 MECOM PAK2 EPHB1 40 VHL PRSS42 ARL6IP5 150 COL25A1 TDGF1 RPSA CCR2 CCR1 IL1RAP IRAK2 20 PTPRG 100 FLNB TF CX3CR1 IL17RD SH3RF1 FGG FANCD2 LIMD1 CCR5 50 0 WDR1 PDGFRA EIF4E FGB AD risk score or log10(P value) AD risk