Table S1. Genes Contributing to the Enrichment Scores of GSEA for Gene-Sets Down-Regulated in Adipose Tissue from Diabetic Compared with Non-Diabetic Co-Twins
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Alternative Acetate Production Pathways in Chlamydomonas Reinhardtii During Dark Anoxia and the Dominant Role of Chloroplasts in Fermentative Acetate Productionw
This article is a Plant Cell Advance Online Publication. The date of its first appearance online is the official date of publication. The article has been edited and the authors have corrected proofs, but minor changes could be made before the final version is published. Posting this version online reduces the time to publication by several weeks. Alternative Acetate Production Pathways in Chlamydomonas reinhardtii during Dark Anoxia and the Dominant Role of Chloroplasts in Fermentative Acetate ProductionW Wenqiang Yang,a,1 Claudia Catalanotti,a Sarah D’Adamo,b Tyler M. Wittkopp,a,c Cheryl J. Ingram-Smith,d Luke Mackinder,a Tarryn E. Miller,b Adam L. Heuberger,e Graham Peers,f Kerry S. Smith,d Martin C. Jonikas,a Arthur R. Grossman,a and Matthew C. Posewitzb a Carnegie Institution for Science, Department of Plant Biology, Stanford, California 94305 b Colorado School of Mines, Department of Chemistry and Geochemistry, Golden, Colorado 80401 c Stanford University, Department of Biology, Stanford, California 94305 d Clemson University, Department of Genetics and Biochemistry, Clemson, South Carolina 29634 e Colorado State University, Proteomics and Metabolomics Facility, Fort Collins, Colorado 80523 f Colorado State University, Department of Biology, Fort Collins, Colorado 80523 ORCID ID: 0000-0001-5600-4076 (W.Y.) Chlamydomonas reinhardtii insertion mutants disrupted for genes encoding acetate kinases (EC 2.7.2.1) (ACK1 and ACK2) and a phosphate acetyltransferase (EC 2.3.1.8) (PAT2, but not PAT1) were isolated to characterize fermentative acetate production. ACK1 and PAT2 were localized to chloroplasts, while ACK2 and PAT1 were shown to be in mitochondria. -
Epidemiology of Mucopolysaccharidoses Update
diagnostics Review Epidemiology of Mucopolysaccharidoses Update Betul Celik 1,2 , Saori C. Tomatsu 2 , Shunji Tomatsu 1 and Shaukat A. Khan 1,* 1 Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; [email protected] (B.C.); [email protected] (S.T.) 2 Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; [email protected] * Correspondence: [email protected]; Tel.: +302-298-7335; Fax: +302-651-6888 Abstract: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a lysosomal enzyme deficiency or malfunction, which leads to the accumulation of glycosaminoglycans in tissues and organs. If not treated at an early stage, patients have various health problems, affecting their quality of life and life-span. Two therapeutic options for MPS are widely used in practice: enzyme replacement therapy and hematopoietic stem cell transplantation. However, early diagnosis of MPS is crucial, as treatment may be too late to reverse or ameliorate the disease progress. It has been noted that the prevalence of MPS and each subtype varies based on geographic regions and/or ethnic background. Each type of MPS is caused by a wide range of the mutational spectrum, mainly missense mutations. Some mutations were derived from the common founder effect. In the previous study, Khan et al. 2018 have reported the epidemiology of MPS from 22 countries and 16 regions. In this study, we aimed to update the prevalence of MPS across the world. We have collected and investigated 189 publications related to the prevalence of MPS via PubMed as of December 2020. In total, data from 33 countries and 23 regions were compiled and analyzed. -
DBT Gene Dihydrolipoamide Branched Chain Transacylase E2
DBT gene dihydrolipoamide branched chain transacylase E2 Normal Function The DBT gene provides instructions for making part of a group of enzymes called the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex. Specifically, the protein produced from the DBT gene forms a critical piece of the enzyme complex called the E2 component. The BCKD enzyme complex is responsible for one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The BCKD enzyme complex is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers. The breakdown of leucine, isoleucine, and valine produces molecules that can be used for energy. Health Conditions Related to Genetic Changes Maple syrup urine disease More than 70 mutations in the DBT gene have been identified in people with maple syrup urine disease, most often in individuals with mild variants of the disorder. These variant forms become apparent later in infancy or childhood, and they lead to delayed development and other health problems if not treated. Mutations in the DBT gene include changes in single DNA building blocks (base pairs) and insertions or deletions of a small amount of DNA in the DBT gene. These changes disrupt the normal function of the E2 component, preventing the BCKD enzyme complex from effectively breaking down leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. -
The Aldehyde Dehydrogenase ALDH2*2 Allele Exhibits Dominance Over ALDH2*1 in Transduced Hela Cells
The aldehyde dehydrogenase ALDH2*2 allele exhibits dominance over ALDH2*1 in transduced HeLa cells. Q Xiao, … , T Johnston, D W Crabb J Clin Invest. 1995;96(5):2180-2186. https://doi.org/10.1172/JCI118272. Research Article Individuals heterozygous or homozygous for the variant aldehyde dehydrogenase (ALDH2) allele (ALDH2*2), which encodes a protein differing only at residue 487 from the normal protein, have decreased ALDH2 activity in liver extracts and experience cutaneous flushing when they drink alcohol. The mechanisms by which this allele exerts its dominant effect is unknown. To study this effect, the human ALDH2*1 cDNA was cloned and the ALDH2*2 allele was generated by site-directed mutagenesis. These cDNAs were transduced using retroviral vectors into HeLa and CV1 cells, which do not express ALDH2. The normal allele directed synthesis of immunoreactive ALDH2 protein (ALDH2E) with the expected isoelectric point. Extracts of these cells contained increased aldehyde dehydrogenase activity with low Km for the aldehyde substrate. The ALDH2*2 allele directed synthesis of mRNA and immunoreactive protein (ALDH2K), but the protein lacked enzymatic activity. When ALDH2*1-expressing cells were transduced with ALDH2*2 vectors, both mRNAs were expressed and immunoreactive proteins with isoelectric points ranging between those of ALDH2E and ALDH2K were present, indicating that the subunits formed heteromers. ALDH2 activity in these cells was reduced below that of the parental ALDH2*1-expressing cells. Thus, the ALDH2*2 allele is sufficient to cause ALDH2 deficiency in vitro. Find the latest version: https://jci.me/118272/pdf The Aldehyde Dehydrogenase ALDH2*2 Allele Exhibits Dominance over ALDH2*1 in Transduced HeLa Cells Qing Xiao, * Henry Weiner,* Timothy Johnston,* and David W. -
Supplemental Figure 1. Vimentin
Double mutant specific genes Transcript gene_assignment Gene Symbol RefSeq FDR Fold- FDR Fold- FDR Fold- ID (single vs. Change (double Change (double Change wt) (single vs. wt) (double vs. single) (double vs. wt) vs. wt) vs. single) 10485013 BC085239 // 1110051M20Rik // RIKEN cDNA 1110051M20 gene // 2 E1 // 228356 /// NM 1110051M20Ri BC085239 0.164013 -1.38517 0.0345128 -2.24228 0.154535 -1.61877 k 10358717 NM_197990 // 1700025G04Rik // RIKEN cDNA 1700025G04 gene // 1 G2 // 69399 /// BC 1700025G04Rik NM_197990 0.142593 -1.37878 0.0212926 -3.13385 0.093068 -2.27291 10358713 NM_197990 // 1700025G04Rik // RIKEN cDNA 1700025G04 gene // 1 G2 // 69399 1700025G04Rik NM_197990 0.0655213 -1.71563 0.0222468 -2.32498 0.166843 -1.35517 10481312 NM_027283 // 1700026L06Rik // RIKEN cDNA 1700026L06 gene // 2 A3 // 69987 /// EN 1700026L06Rik NM_027283 0.0503754 -1.46385 0.0140999 -2.19537 0.0825609 -1.49972 10351465 BC150846 // 1700084C01Rik // RIKEN cDNA 1700084C01 gene // 1 H3 // 78465 /// NM_ 1700084C01Rik BC150846 0.107391 -1.5916 0.0385418 -2.05801 0.295457 -1.29305 10569654 AK007416 // 1810010D01Rik // RIKEN cDNA 1810010D01 gene // 7 F5 // 381935 /// XR 1810010D01Rik AK007416 0.145576 1.69432 0.0476957 2.51662 0.288571 1.48533 10508883 NM_001083916 // 1810019J16Rik // RIKEN cDNA 1810019J16 gene // 4 D2.3 // 69073 / 1810019J16Rik NM_001083916 0.0533206 1.57139 0.0145433 2.56417 0.0836674 1.63179 10585282 ENSMUST00000050829 // 2010007H06Rik // RIKEN cDNA 2010007H06 gene // --- // 6984 2010007H06Rik ENSMUST00000050829 0.129914 -1.71998 0.0434862 -2.51672 -
Combined Treatment of Isoflavone Supplementation and Exercise
Yoon et al. Journal of the International Society of Sports Nutrition 2014, 11:29 http://www.jissn.com/content/11/1/29 RESEARCH ARTICLE Open Access Combined treatment of isoflavone supplementation and exercise restores the changes in hepatic protein expression in ovariectomized rats - a proteomics approach Sun Yoon1, Joomin Lee2 and Seung-Min Lee1* Abstract Background: Postmenopausal women experience adverse physiological changes caused by estrogen deprivation. Here, we hypothesized that the administration of isoflavone, a phytoestrogn, and/or physical exercise could reverse changes in the levels of hepatic enzymes disturbed by loss of estrogen to ameliorate postmenopause-related health problems. Methods: Thirty-week-old female Sprague–Dawley rats were divided into five groups: a sham-operated (SHAM) group, ovariectomized groups on a regular diet with exercise (EXE) and without exercise (OVX), and ovariectomized groups on an isoflavone supplemented diet with (ISO + EXE) and without exercise (ISO). Proteomic tools were employed to identify candidate hepatic proteins that were differentially expressed among the five animal groups. Results: INMT was detected in the SHAM but not in all of the ovariectomized rats. Seven proteins (PPIA, AKR1C3, ALDH2, PSME2, BUCS1, OTC, and GAMT) were identified to have differential expression among the groups. When compared to the SHAM group, the ovariectomy elevated the levels of PPIA, BUCS1, PSME2, AKR1C3, and GAMT while decreasing ALDH2 and OTC. Among these OVX-induced changes, OVX-increased BUCS1 and GAMT levels were noticeably decreased by ISO or EXE and further greatly down-regulated by ISO + EXE. In the case of PSME2, ISO and EXE further increased OVX-upregulated expression levels but ISO + EXE greatly reduced OVX-increased levels. -
Thiamine Dependency and Related Gene Mutations: Recent Aspects
Int J Anal Bio-Sci Vol. 3, No 4 (2015) 〈Review Article〉 Thiamine dependency and related gene mutations: recent aspects Sachiko Kiuchi1, Hiroshi Ihara1, Yoshikazu Nishiguchi2, Nobue Ito3, Hiromitsu Yokota3 and Naotaka Hashizume4 Summary Thiamine dependency is an inherited metabolic disorder from which patients exhibit severe symptoms of deficiency, although they are fed more than the normal requirement of this vitamin. Deficiency symptoms can be treated with pharmacologic doses of thiamine as high as 100 to 1,000 times the Dietary Reference Values. Thiamine dependency is nowadays classified as a disorder caused by genetic mutations affecting thiamine-dependent enzymes or thiamine transporter, which transports thiamine to cells. The former mutation on enzyme is known as a pyruvate dehydrogenase complex deficiency (i.e., congenital lactic acidemia and Leigh syndrome) and a deficiency in branched- chain α-ketoacid dehydrogenase complex (i.e., maple syrup urine disease). The latter are known as mutations in thiamine transporter gene that makes protein transporting thiamine into cells (encoded by SLC19A2 and SLC19A3 genes) and protein transporting thiamine diphosphate into the mitochon- dria (encoded by SLC25A19 gene). Thiamine-responsive megaloblastic anemia (TRMA), an autosomal recessive disease, is caused by loss of functional mutation in the SLC19A2 (ThTr-1). Key words: Vitamin B1 dependency, Thiamine deficiency, Maple syrup urine disease, Megaloblastic anemia, Thiamine transporter 1. Introduction the normal daily requirement from diets, dietary supplements, or intravenous dosage. The deficiency To maintain normal carbohydrate metabolism in symptoms were better treated by taking amounts of the body, we have to ingest thiamine from our diet. thiamine 100-fold greater or more than that of the The daily required amounts are 1.4 mg (4.2 µmol) for daily requirement, but the symptoms would reappear men and 1.1 mg (3.3 µmol) for women for Japanese if the treatment was stopped4. -
Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
cancers Article Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma 1, 1, 1 1 1 Lan Wang y, Anudeep Yekula y, Koushik Muralidharan , Julia L. Small , Zachary S. Rosh , Keiko M. Kang 1,2, Bob S. Carter 1,* and Leonora Balaj 1,* 1 Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA; [email protected] (L.W.); [email protected] (A.Y.); [email protected] (K.M.); [email protected] (J.L.S.); [email protected] (Z.S.R.); [email protected] (K.M.K.) 2 School of Medicine, University of California San Diego, San Diego, CA 92092, USA * Correspondence: [email protected] (B.S.C.); [email protected] (L.B.) These authors contributed equally. y Received: 11 March 2020; Accepted: 7 May 2020; Published: 13 May 2020 Abstract: Sequencing studies have provided novel insights into the heterogeneous molecular landscape of glioblastoma (GBM), unveiling a subset of patients with gene fusions. Tissue biopsy is highly invasive, limited by sampling frequency and incompletely representative of intra-tumor heterogeneity. Extracellular vesicle-based liquid biopsy provides a minimally invasive alternative to diagnose and monitor tumor-specific molecular aberrations in patient biofluids. Here, we used targeted RNA sequencing to screen GBM tissue and the matched plasma of patients (n = 9) for RNA fusion transcripts. We identified two novel fusion transcripts in GBM tissue and five novel fusions in the matched plasma of GBM patients. The fusion transcripts FGFR3-TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma. -
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. -
(12) United States Patent (10) Patent No.: US 8,323,640 B2 Sakuraba Et Al
USOO8323640B2 (12) United States Patent (10) Patent No.: US 8,323,640 B2 Sakuraba et al. (45) Date of Patent: *Dec. 4, 2012 (54) HIGHLY FUNCTIONAL ENZYME HAVING OTHER PUBLICATIONS O-GALACTOSIDASE ACTIVITY Broun et al., Catalytic plasticity of fatty acid modification enzymes (75) Inventors: Hitoshi Sakuraba, Abiko (JP); Youichi underlying chemical diversity of plant lipids. Science, 1998, vol. 282: Tajima, Tokyo (JP); Mai Ito, Tokyo 1315-1317. (JP); Seiichi Aikawa, Tokyo (JP); Cameron ER. Recent advances in transgenic technology. 1997, vol. T: 253-265. Fumiko Aikawa, Tokyo (JP) Chica et al., Semi-rational approaches to engineering enzyme activ (73) Assignees: Tokyo Metropolitan Organization For ity: combining the benefits of directed evolution and rational design. Curr, opi. Biotechnol., 2005, vol. 16:378-384. Medical Research, Tokyo (JP); Altif Couzin et al. As Gelsinger case ends, Gene therapy Suffers another Laboratories, Tokyo (JP) blow. Science, 2005, vol. 307: 1028. Devos et al., Practical Limits of Function prediction. Proteins: Struc (*) Notice: Subject to any disclaimer, the term of this ture, Function, and Genetics. 2000, vol. 41: 98-107. patent is extended or adjusted under 35 Donsante et al., AAV vector integration sites in mouse hapatocellular U.S.C. 154(b) by 0 days. carcinoma. Science, 2007. vol. 317: 477. Juengst ET., What next for human gene therapy? BMJ., 2003, vol. This patent is Subject to a terminal dis 326: 1410-1411. claimer. Kappel et al., Regulating gene expression in transgenic animals. Current Opinion in Biotechnology 1992, vol. 3: 548-553. (21) Appl. No.: 13/052,632 Kimmelman J. Recent developments in gene transfer: risk and eth ics. -
Functional Parsing of Driver Mutations in the Colorectal Cancer Genome Reveals Numerous Suppressors of Anchorage-Independent
Supplementary information Functional parsing of driver mutations in the colorectal cancer genome reveals numerous suppressors of anchorage-independent growth Ugur Eskiocak1, Sang Bum Kim1, Peter Ly1, Andres I. Roig1, Sebastian Biglione1, Kakajan Komurov2, Crystal Cornelius1, Woodring E. Wright1, Michael A. White1, and Jerry W. Shay1. 1Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039. 2Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054. Supplementary Figure S1. K-rasV12 expressing cells are resistant to p53 induced apoptosis. Whole-cell extracts from immortalized K-rasV12 or p53 down regulated HCECs were immunoblotted with p53 and its down-stream effectors after 10 Gy gamma-radiation. ! Supplementary Figure S2. Quantitative validation of selected shRNAs for their ability to enhance soft-agar growth of immortalized shTP53 expressing HCECs. Each bar represents 8 data points (quadruplicates from two separate experiments). Arrows denote shRNAs that failed to enhance anchorage-independent growth in a statistically significant manner. Enhancement for all other shRNAs were significant (two tailed Studentʼs t-test, compared to none, mean ± s.e.m., P<0.05)." ! Supplementary Figure S3. Ability of shRNAs to knockdown expression was demonstrated by A, immunoblotting for K-ras or B-E, Quantitative RT-PCR for ERICH1, PTPRU, SLC22A15 and SLC44A4 48 hours after transfection into 293FT cells. Two out of 23 tested shRNAs did not provide any knockdown. " ! Supplementary Figure S4. shRNAs against A, PTEN and B, NF1 do not enhance soft agar growth in HCECs without oncogenic manipulations (Student!s t-test, compared to none, mean ± s.e.m., ns= non-significant). -
PEX5 Regulates Autophagy Via the Mtorc1-TFEB Axis During Starvation
Eun et al. Experimental & Molecular Medicine (2018) 50:4 DOI 10.1038/s12276-017-0007-8 Experimental & Molecular Medicine ARTICLE Open Access PEX5 regulates autophagy via the mTORC1-TFEB axis during starvation So Young Eun1,JoonNoLee2,In-KooNam2, Zhi-qiang Liu1,Hong-SeobSo 1, Seong-Kyu Choe1 and RaeKil Park2 Abstract Defects in the PEX5 gene impair the import of peroxisomal matrix proteins, leading to nonfunctional peroxisomes and other associated pathological defects such as Zellweger syndrome. Although PEX5 regulates autophagy process in a stress condition, the mechanisms controlling autophagy by PEX5 under nutrient deprivation are largely unknown. Herein, we show a novel function of PEX5 in the regulation of autophagy via Transcription Factor EB (TFEB). Under serum-starved conditions, when PEX5 is depleted, the mammalian target of rapamycin (mTORC1) inhibitor TSC2 is downregulated, which results in increased phosphorylation of the mTORC1 substrates, including 70S6K, S6K, and 4E- BP-1. mTORC1 activation further suppresses the nuclear localization of TFEB, as indicated by decreased mRNA levels of TFEB, LIPA, and LAMP1. Interestingly, peroxisomal mRNA and protein levels are also reduced by TFEB inactivation, indicating that TFEB might control peroxisome biogenesis at a transcriptional level. Conversely, pharmacological inhibition of mTOR resulting from PEX5 depletion during nutrient starvation activates TFEB by promoting nuclear localization of the protein. In addition, mTORC1 inhibition recovers the damaged-peroxisome biogenesis. These data suggest that PEX5 may be a critical regulator of lysosomal gene expression and autophagy through the mTOR-TFEB- autophagy axis under nutrient deprivation. 1234567890():,; 1234567890():,; Introduction Mitochondrial antiviral-signaling protein (MAVS) func- Peroxisome is an essential cellular organelle for per- tions as an antiviral signaling platform to induce the forming various metabolic activities, including oxidation interferon-independent signaling pathways4.