Calorie Restriction Prevents Metabolic Ageing Caused by Abnormal SIRT1 Function in Adipose Tissues Cheng Xu , Yu Cai , Pengchen
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1 2 3 4 5 6 7 Supplementary Information for 8 9 Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic 10 retinopathy 11 12 *Samuel A. Mills, *Andrew I. Jobling, *Michael A. Dixon, Bang V. Bui, Kirstan A. Vessey, Joanna A. Phipps, 13 Ursula Greferath, Gene Venables, Vickie H.Y. Wong, Connie H.Y. Wong, Zheng He, Flora Hui, James C. 14 Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher 15 * Joint first authors 16 17 Corresponding author: 18 Prof. Erica L. Fletcher. Department of Anatomy & Neuroscience. The University of Melbourne, Grattan St, 19 Parkville 3010, Victoria, Australia. 20 Email: [email protected] ; Tel: +61-3-8344-3218; Fax: +61-3-9347-5219 21 22 This PDF file includes: 23 24 Supplementary text 25 Figures S1 to S10 26 Tables S1 to S7 27 Legends for Movies S1 to S2 28 SI References 29 30 Other supplementary materials for this manuscript include the following: 31 32 Movies S1 to S2 33 34 35 36 1 1 Supplementary Information Text 2 Materials and Methods 3 Microglial process movement on retinal vessels 4 Dark agouti rats were anaesthetized, injected intraperitoneally with rhodamine B (Sigma-Aldrich) to label blood 5 vessels and retinal explants established as described in the main text. Retinal microglia were labelled with Iba-1 6 and imaging performed on an inverted confocal microscope (Leica SP5). Baseline images were taken for 10 7 minutes, followed by the addition of PBS (10 minutes) and then either fractalkine or fractalkine + candesartan 8 (10 minutes) using concentrations outlined in the main text. -
Discovery of an Alternate Metabolic Pathway for Urea Synthesis in Adult Aedes Aegypti Mosquitoes
Discovery of an alternate metabolic pathway for urea synthesis in adult Aedes aegypti mosquitoes Patricia Y. Scaraffia*†‡, Guanhong Tan§, Jun Isoe*†, Vicki H. Wysocki*§, Michael A. Wells*†, and Roger L. Miesfeld*† Departments of §Chemistry and *Biochemistry and Molecular Biophysics and †Center for Insect Science, University of Arizona, Tucson, AZ 85721-0088 Edited by Anthony A. James, University of California, Irvine, CA, and approved December 4, 2007 (received for review August 27, 2007) We demonstrate the presence of an alternate metabolic pathway We previously reported that mosquitoes dispose of toxic for urea synthesis in Aedes aegypti mosquitoes that converts uric ammonia through glutamine (Gln) and proline (Pro) synthesis, acid to urea via an amphibian-like uricolytic pathway. For these along with excretion of ammonia, uric acid, and urea (20). By studies, female mosquitoes were fed a sucrose solution containing using labeled isotopes and mass spectrometry techniques (21), 15 15 15 15 15 NH4Cl, [5- N]-glutamine, [ N]-proline, allantoin, or allantoic we have recently determined how the N from NH4Cl is acid. At 24 h after feeding, the feces were collected and analyzed incorporated into the amide side chain of Gln, and then into Pro, in a mass spectrometer. Specific enzyme inhibitors confirmed that in Ae. aegypti (22). In the present article we demonstrate that the 15 15 15 mosquitoes incorporate N from NH4Cl into [5- N]-glutamine nitrogen of the amide group of Gln contributes to uric acid and use the 15N of the amide group of glutamine to produce synthesis in mosquitoes and, surprisingly, that uric acid can be 15 labeled uric acid. -
IL21R Expressing CD14+CD16+ Monocytes Expand in Multiple
Plasma Cell Disorders SUPPLEMENTARY APPENDIX IL21R expressing CD14 +CD16 + monocytes expand in multiple myeloma patients leading to increased osteoclasts Marina Bolzoni, 1 Domenica Ronchetti, 2,3 Paola Storti, 1,4 Gaetano Donofrio, 5 Valentina Marchica, 1,4 Federica Costa, 1 Luca Agnelli, 2,3 Denise Toscani, 1 Rosanna Vescovini, 1 Katia Todoerti, 6 Sabrina Bonomini, 7 Gabriella Sammarelli, 1,7 Andrea Vecchi, 8 Daniela Guasco, 1 Fabrizio Accardi, 1,7 Benedetta Dalla Palma, 1,7 Barbara Gamberi, 9 Carlo Ferrari, 8 Antonino Neri, 2,3 Franco Aversa 1,4,7 and Nicola Giuliani 1,4,7 1Myeloma Unit, Dept. of Medicine and Surgery, University of Parma; 2Dept. of Oncology and Hemato-Oncology, University of Milan; 3Hematology Unit, “Fondazione IRCCS Ca’ Granda”, Ospedale Maggiore Policlinico, Milan; 4CoreLab, University Hospital of Parma; 5Dept. of Medical-Veterinary Science, University of Parma; 6Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture; 7Hematology and BMT Center, University Hospital of Parma; 8Infectious Disease Unit, University Hospital of Parma and 9“Dip. Oncologico e Tecnologie Avanzate”, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy ©2017 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2016.153841 Received: August 5, 2016. Accepted: December 23, 2016. Pre-published: January 5, 2017. Correspondence: [email protected] SUPPLEMENTAL METHODS Immunophenotype of BM CD14+ in patients with monoclonal gammopathies. Briefly, 100 μl of total BM aspirate was incubated in the dark with anti-human HLA-DR-PE (clone L243; BD), anti-human CD14-PerCP-Cy 5.5, anti-human CD16-PE-Cy7 (clone B73.1; BD) and anti-human CD45-APC-H 7 (clone 2D1; BD) for 20 min. -
Annexin A2 Depletion Delays EGFR Endocytic Trafficking Via Cofilin
Oncogene (2014) 33, 2610–2619 & 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14 www.nature.com/onc ORIGINAL ARTICLE Annexin A2 depletion delays EGFR endocytic trafficking via cofilin activation and enhances EGFR signaling and metastasis formation M de Graauw1, L Cao2,5, L Winkel3,5, MHAM van Miltenburg4,SEleDe´ve´ dec1, M Klop1,KYan2, C Pont1, V-M Rogkoti1, A Tijsma1, A Chaudhuri1, R Lalai1, L Price1, F Verbeek2 and B van de Water1 Enhanced epidermal growth factor receptor (EGFR) activity has been strongly linked to breast cancer progression and mediators of EGFR endocytosis may well be involved. We developed a semi-automated high-content fluorescence microscopy-based EGFR endocytosis screen to identify proteins that mediate EGFR endocytosis in human HBL100 breast cancer cells. Knockdown of 172 individual endocytosis and actin-regulatory genes with small interfering RNAs led to the identification of 14 genes of which the contribution to EGFR endocytosis in breast cancer is until now poorly defined, including DNAJC6, GDI2, FGD6, HAX1, NECAP2 and AnxA2. We show that depletion of the actin and endocytosis regulatory protein annexin A2 (AnxA2) in a panel of four triple negative breast cancer (TNBC) cell lines affected EGFR endocytosis. Depletion of AnxA2 in the aggressive and highly metastatic MDA-MB-231 TNBC cell line resulted in the inhibition of EGFR transport beyond the early endosomes. This inhibition coincided with enhanced epidermal growth factor (EGF)-induced cell migration and downstream signaling via c-Jun N-terminal kinase (JNK) and Akt. Moreover, AnxA2 knockdown increased lung metastasis formation in mice. The effect of AnxA2 knockdown on EGFR endocytosis in MDA-MB-231 was related to dephosphorylation/activation of the actin-severing protein cofilin, as re-expression of an inactive S3E- cofilin mutant, but not an active S3A-cofilin mutant, re-established EGFR endocytosis to control levels. -
Genome-Wide Association and Transcriptome Studies Identify Candidate Genes and Pathways for Feed Conversion Ratio in Pigs
Miao et al. BMC Genomics (2021) 22:294 https://doi.org/10.1186/s12864-021-07570-w RESEARCH ARTICLE Open Access Genome-wide association and transcriptome studies identify candidate genes and pathways for feed conversion ratio in pigs Yuanxin Miao1,2,3, Quanshun Mei1,2, Chuanke Fu1,2, Mingxing Liao1,2,4, Yan Liu1,2, Xuewen Xu1,2, Xinyun Li1,2, Shuhong Zhao1,2 and Tao Xiang1,2* Abstract Background: The feed conversion ratio (FCR) is an important productive trait that greatly affects profits in the pig industry. Elucidating the genetic mechanisms underpinning FCR may promote more efficient improvement of FCR through artificial selection. In this study, we integrated a genome-wide association study (GWAS) with transcriptome analyses of different tissues in Yorkshire pigs (YY) with the aim of identifying key genes and signalling pathways associated with FCR. Results: A total of 61 significant single nucleotide polymorphisms (SNPs) were detected by GWAS in YY. All of these SNPs were located on porcine chromosome (SSC) 5, and the covered region was considered a quantitative trait locus (QTL) region for FCR. Some genes distributed around these significant SNPs were considered as candidates for regulating FCR, including TPH2, FAR2, IRAK3, YARS2, GRIP1, FRS2, CNOT2 and TRHDE. According to transcriptome analyses in the hypothalamus, TPH2 exhibits the potential to regulate intestinal motility through serotonergic synapse and oxytocin signalling pathways. In addition, GRIP1 may be involved in glutamatergic and GABAergic signalling pathways, which regulate FCR by affecting appetite in pigs. Moreover, GRIP1, FRS2, CNOT2,andTRHDE may regulate metabolism in various tissues through a thyroid hormone signalling pathway. -
Gene Symbol Category ACAN ECM ADAM10 ECM Remodeling-Related ADAM11 ECM Remodeling-Related ADAM12 ECM Remodeling-Related ADAM15 E
Supplementary Material (ESI) for Integrative Biology This journal is (c) The Royal Society of Chemistry 2010 Gene symbol Category ACAN ECM ADAM10 ECM remodeling-related ADAM11 ECM remodeling-related ADAM12 ECM remodeling-related ADAM15 ECM remodeling-related ADAM17 ECM remodeling-related ADAM18 ECM remodeling-related ADAM19 ECM remodeling-related ADAM2 ECM remodeling-related ADAM20 ECM remodeling-related ADAM21 ECM remodeling-related ADAM22 ECM remodeling-related ADAM23 ECM remodeling-related ADAM28 ECM remodeling-related ADAM29 ECM remodeling-related ADAM3 ECM remodeling-related ADAM30 ECM remodeling-related ADAM5 ECM remodeling-related ADAM7 ECM remodeling-related ADAM8 ECM remodeling-related ADAM9 ECM remodeling-related ADAMTS1 ECM remodeling-related ADAMTS10 ECM remodeling-related ADAMTS12 ECM remodeling-related ADAMTS13 ECM remodeling-related ADAMTS14 ECM remodeling-related ADAMTS15 ECM remodeling-related ADAMTS16 ECM remodeling-related ADAMTS17 ECM remodeling-related ADAMTS18 ECM remodeling-related ADAMTS19 ECM remodeling-related ADAMTS2 ECM remodeling-related ADAMTS20 ECM remodeling-related ADAMTS3 ECM remodeling-related ADAMTS4 ECM remodeling-related ADAMTS5 ECM remodeling-related ADAMTS6 ECM remodeling-related ADAMTS7 ECM remodeling-related ADAMTS8 ECM remodeling-related ADAMTS9 ECM remodeling-related ADAMTSL1 ECM remodeling-related ADAMTSL2 ECM remodeling-related ADAMTSL3 ECM remodeling-related ADAMTSL4 ECM remodeling-related ADAMTSL5 ECM remodeling-related AGRIN ECM ALCAM Cell-cell adhesion ANGPT1 Soluble factors and receptors -
Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes. -
Proquest Dissertations
urn u Ottawa L'Universitd canadienne Canada's university FACULTE DES ETUDES SUPERIEURES l^^l FACULTY OF GRADUATE AND ET POSTDOCTORALES u Ottawa POSTDOCTORAL STUDIES I.'University emiadienne Canada's university Charles Gyamera-Acheampong AUTEUR DE LA THESE / AUTHOR OF THESIS Ph.D. (Biochemistry) GRADE/DEGREE Biochemistry, Microbiology and Immunology FACULTE, ECOLE, DEPARTEMENT / FACULTY, SCHOOL, DEPARTMENT The Physiology and Biochemistry of the Fertility Enzyme Proprotein Convertase Subtilisin/Kexin Type 4 TITRE DE LA THESE / TITLE OF THESIS M. Mbikay TIRECTWRTDIRICTR^ CO-DIRECTEUR (CO-DIRECTRICE) DE LA THESE / THESIS CO-SUPERVISOR EXAMINATEURS (EXAMINATRICES) DE LA THESE/THESIS EXAMINERS A. Basak G. Cooke F .Kan V. Mezl Gary W. Slater Le Doyen de la Faculte des etudes superieures et postdoctorales / Dean of the Faculty of Graduate and Postdoctoral Studies Library and Archives Bibliotheque et 1*1 Canada Archives Canada Published Heritage Direction du Branch Patrimoine de I'edition 395 Wellington Street 395, rue Wellington OttawaONK1A0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre reference ISBN: 978-0-494-59504-6 Our file Notre reference ISBN: 978-0-494-59504-6 NOTICE: AVIS: The author has granted a non L'auteur a accorde une licence non exclusive exclusive license allowing Library and permettant a la Bibliotheque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par I'lnternet, prefer, telecommunication or on the Internet, distribuer et vendre des theses partout dans le loan, distribute and sell theses monde, a des fins commerciales ou autres, sur worldwide, for commercial or non support microforme, papier, electronique et/ou commercial purposes, in microform, autres formats. -
Conservation and Divergence of ADAM Family Proteins in the Xenopus Genome
Wei et al. BMC Evolutionary Biology 2010, 10:211 http://www.biomedcentral.com/1471-2148/10/211 RESEARCH ARTICLE Open Access ConservationResearch article and divergence of ADAM family proteins in the Xenopus genome Shuo Wei*1, Charles A Whittaker2, Guofeng Xu1, Lance C Bridges1,3, Anoop Shah1, Judith M White1 and Douglas W DeSimone1 Abstract Background: Members of the disintegrin metalloproteinase (ADAM) family play important roles in cellular and developmental processes through their functions as proteases and/or binding partners for other proteins. The amphibian Xenopus has long been used as a model for early vertebrate development, but genome-wide analyses for large gene families were not possible until the recent completion of the X. tropicalis genome sequence and the availability of large scale expression sequence tag (EST) databases. In this study we carried out a systematic analysis of the X. tropicalis genome and uncovered several interesting features of ADAM genes in this species. Results: Based on the X. tropicalis genome sequence and EST databases, we identified Xenopus orthologues of mammalian ADAMs and obtained full-length cDNA clones for these genes. The deduced protein sequences, synteny and exon-intron boundaries are conserved between most human and X. tropicalis orthologues. The alternative splicing patterns of certain Xenopus ADAM genes, such as adams 22 and 28, are similar to those of their mammalian orthologues. However, we were unable to identify an orthologue for ADAM7 or 8. The Xenopus orthologue of ADAM15, an active metalloproteinase in mammals, does not contain the conserved zinc-binding motif and is hence considered proteolytically inactive. We also found evidence for gain of ADAM genes in Xenopus as compared to other species. -
DYSREGULATION of LONG-CHAIN ACYL-Coa SYNTHETASES in CANCER and THEIR TARGETING STRATEGIES in ANTICANCER THERAPY Md Amir Hossain1, Jun Ma2, Yong Yang1 1
Hossain et al RJLBPCS 2020 www.rjlbpcs.com Life Science Informatics Publications Original Review Article DOI: 10.26479/2020.0603.06 DYSREGULATION OF LONG-CHAIN ACYL-CoA SYNTHETASES IN CANCER AND THEIR TARGETING STRATEGIES IN ANTICANCER THERAPY Md Amir Hossain1, Jun Ma2, Yong Yang1 1. Academic Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, China. 2. Ningxia Baoshihua Hospital, Ningxia, China. ABSTRACT: Cancer is a leading cause of death worldwide, and the number of cases globally continues to increase. Cancer is caused by certain changes in genes that are involved in controlling cell functions and cell division. Notably, metabolic dysregulation is one the hallmarks of cancer, and increases in fatty acid metabolism have been demonstrated to promote the growth and survival of a variety of cancers. In human, fatty acids either can be breakdown into acetyl-CoA through catabolic metabolism and aid in ATP generation or in the anabolic metabolism they can incorporate into triacylglycerol and phospholipid. Importantly, both of these pathways need activation of fatty acids, and the key players in this activation of fatty acids are the long-chain acyl-CoA synthetases (ACSLs) that are commonly dysregulated in cancer and associated with oncogenesis and survival. Therefore, it provides a rationale to target ACSLs in cancer. This review summarizes the current understanding of long-chain acyl-CoA synthetases in cancer and their targeting opportunities. KEYWORDS: Acyl-CoA synthetases, cancer, fatty acid, lipid metabolism. Article History: Received: April 15, 2020; Revised: May 10, 2020; Accepted: May 30, 2020. Corresponding Author: Prof. Yong Yang* Academic Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, China. -
Nfletffillfl Sm of Nuelieotfl Dles
Nfletffillflsm of Nuelieotfl dles ucleotides \f consistof a nitrogenousbase, a | \ pentose and a phosphate. The pentose sugaris D-ribosein ribonucleotidesof RNAwhile in deoxyribonucleotides(deoxynucleotides) of i Aspariaie--'N.,,,t .J . DNA, the sugaris 2-deoxyD-ribose. Nucleotides t participate in almost all the biochemical processes/either directly or indirectly.They are the structuralcomponents of nucleicacids (DNA, Y RNA), coenzymes, and are involved in tne Glutamine regulationof severalmetabolic reactions. Fig. 17.1 : The sources of individuat atoms in purine ring. (Note : Same colours are used in the syntheticpathway Fig. lZ.2). n T. C4, C5 and N7 are contributedby glycine. Many compoundscontribute to the purine ring of the nucleotides(Fig.t7.l). 5. C6 directly comes from COr. 1. purine N1 of is derivedfrom amino group It should be rememberedthat purine bases of aspartate. are not synthesizedas such,but they are formed as ribonucleotides. The purines 2. C2 and Cs arise from formate of N10- are built upon a formyl THF. pre-existing ribose S-phosphate. Liver is the major site for purine nucleotide synthesis. 3. N3 and N9 are obtainedfrom amide group Erythrocytes,polymorphonuclear leukocytes and of glutamine. brain cannot producepurines. 388 BIOCHEMISTF|Y m-gg-o-=_ |l Formylglycinamide ribosyl S-phosphate Kn H) Glutam H \-Y OH +ATt OH OH Glutame cl-D-Ribose-S-phosphate + ADP orr-l t'1 PRPPsYnthetase ,N o"t*'] \cH + Hrcl-itl HN:C-- O EO-qn2-O.- H -NH l./ \l KH H) I u \.]_j^/ r,\-iEl-/^\-td Ribose5-P II Formylglycinamidineribosyl-s-phosphate -
AGPAT2 Gene 1-Acylglycerol-3-Phosphate O-Acyltransferase 2
AGPAT2 gene 1-acylglycerol-3-phosphate O-acyltransferase 2 Normal Function The AGPAT2 gene provides instructions for making an enzyme that is found in many of the body's cells and tissues. It plays a critical role in the growth and development of adipocytes, which are cells that store fats for energy. Adipocytes are the major component of the body's fatty (adipose) tissue. The AGPAT2 enzyme is part of a chemical pathway in many cells that produces two important types of fats (lipids): glycerophospholipids and triacylglycerols. Glycerophospholipids are the major component of cell membranes and are involved in chemical signaling within cells. Triacylglycerols (also known as triglycerides) are fat molecules that are stored in adipocytes for later conversion to energy. The AGPAT2 enzyme is responsible for a particular chemical reaction in the production of these two types of lipids. Specifically, the enzyme helps convert a molecule called lysophosphatidic acid (LPA) to another molecule, phosphatidic acid (PA). Additional reactions convert phosphatidic acid to glycerophospholipids and triacylglycerols. Health Conditions Related to Genetic Changes Congenital generalized lipodystrophy At least 26 mutations in the AGPAT2 gene have been identified in people with congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) type 1. This rare condition is characterized by an almost total absence of adipose tissue and a very muscular appearance. A shortage of adipose tissue leads to multiple health problems, including high levels of triglycerides circulating in the bloodstream (hypertriglyceridemia) and diabetes mellitus. The AGPAT2 gene mutations that cause congenital generalized lipodystrophy type 1 greatly reduce or eliminate the activity of the AGPAT2 enzyme.