Supplementary Table 1: List of the 316 Genes Regulated During Hyperglycemic Euinsulinemic Clamp in Skeletal Muscle
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Stem Cell Factor Is Selectively Secreted by Arterial Endothelial Cells in Bone Marrow
ARTICLE DOI: 10.1038/s41467-018-04726-3 OPEN Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow Chunliang Xu1,2, Xin Gao1,2, Qiaozhi Wei1,2, Fumio Nakahara 1,2, Samuel E. Zimmerman3,4, Jessica Mar3,4 & Paul S. Frenette 1,2,5 Endothelial cells (ECs) contribute to haematopoietic stem cell (HSC) maintenance in bone marrow, but the differential contributions of EC subtypes remain unknown, owing to the lack 1234567890():,; of methods to separate with high purity arterial endothelial cells (AECs) from sinusoidal endothelial cells (SECs). Here we show that the combination of podoplanin (PDPN) and Sca-1 expression distinguishes AECs (CD45− Ter119− Sca-1bright PDPN−) from SECs (CD45− Ter119− Sca-1dim PDPN+). PDPN can be substituted for antibodies against the adhesion molecules ICAM1 or E-selectin. Unexpectedly, prospective isolation reveals that AECs secrete nearly all detectable EC-derived stem cell factors (SCF). Genetic deletion of Scf in AECs, but not SECs, significantly reduced functional HSCs. Lineage-tracing analyses suggest that AECs and SECs self-regenerate independently after severe genotoxic insults, indicating the per- sistence of, and recovery from, radio-resistant pre-specified EC precursors. AEC-derived SCF also promotes HSC recovery after myeloablation. These results thus uncover heterogeneity in the contribution of ECs in stem cell niches. 1 The Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY 10461, USA. 2 Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA. 3 Department of Systems and Computational Biology, Albert Einstein College of Medicine, New York, NY 10461, USA. -
Supplementary Materials: Evaluation of Cytotoxicity and Α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids
Supplementary Materials: Evaluation of cytotoxicity and α-glucosidase inhibitory activity of amide and polyamino-derivatives of lupane triterpenoids Oxana B. Kazakova1*, Gul'nara V. Giniyatullina1, Akhat G. Mustafin1, Denis A. Babkov2, Elena V. Sokolova2, Alexander A. Spasov2* 1Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71, pr. Oktyabrya, 450054 Ufa, Russian Federation 2Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, Volgograd 400087, Russian Federation Correspondence Prof. Dr. Oxana B. Kazakova Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences 71 Prospeсt Oktyabrya Ufa, 450054 Russian Federation E-mail: [email protected] Prof. Dr. Alexander A. Spasov Scientific Center for Innovative Drugs of the Volgograd State Medical University 39 Novorossiyskaya st. Volgograd, 400087 Russian Federation E-mail: [email protected] Figure S1. 1H and 13C of compound 2. H NH N H O H O H 2 2 Figure S2. 1H and 13C of compound 4. NH2 O H O H CH3 O O H H3C O H 4 3 Figure S3. Anticancer screening data of compound 2 at single dose assay 4 Figure S4. Anticancer screening data of compound 7 at single dose assay 5 Figure S5. Anticancer screening data of compound 8 at single dose assay 6 Figure S6. Anticancer screening data of compound 9 at single dose assay 7 Figure S7. Anticancer screening data of compound 12 at single dose assay 8 Figure S8. Anticancer screening data of compound 13 at single dose assay 9 Figure S9. Anticancer screening data of compound 14 at single dose assay 10 Figure S10. -
Molecular Clock Is Involved in Predictive Circadian Adjustment of Renal Function
Molecular clock is involved in predictive circadian adjustment of renal function Annie Mercier Zubera,1,2, Gabriel Centenoa,2, Sylvain Pradervandb, Svetlana Nikolaevaa,c, Lionel Maquelina, Le´ onard Cardinauxa, Olivier Bonnya,d, and Dmitri Firsova,3 aDepartment of Pharmacology and Toxicology, University of Lausanne, 1005 Lausanne, Switzerland; bDNA Array Facility, University of Lausanne, 1015 Lausanne, Switzerland; cInstitute of Evolutionary Physiology and Biochemistry, 194223 St-Petersburg, Russia; and dService of Nephrology, Lausanne University Hospital, 1005 Lausanne, Switzerland Edited by Maurice B. Burg, National Heart, Lung, and Blood Institute, Bethesda, MD, and approved August 6, 2009 (received for review May 4, 2009) Renal excretion of water and major electrolytes exhibits a significant anticipate upcoming circadian environmental challenges (activity, circadian rhythm. This functional periodicity is believed to result, at feeding, etc). least in part, from circadian changes in secretion/reabsorption capac- The most obvious manifestation of circadian rhythmicity of renal ities of the distal nephron and collecting ducts. Here, we studied the function is a well-marked difference in the volume of urine forma- molecular mechanisms underlying circadian rhythms in the distal tion/excretion between the day and the night. The urinary excretion nephron segments, i.e., distal convoluted tubule (DCT) and connect- ϩ ϩ Ϫ Ϫ 2ϩ 2ϩ of all major solutes (Na ,K ,Cl , urea, PO4 ,Ca ,Mg )also ing tubule (CNT) and the cortical collecting duct (CCD). Temporal follows a circadian oscillating pattern. Although, renal excretion expression analysis performed on microdissected mouse DCT/CNT or rhythms are apparently synchronized with circadian rhythms of CCD revealed a marked circadian rhythmicity in the expression of a activity/feeding, they have been shown to persist over long periods large number of genes crucially involved in various homeostatic of time under experimental conditions in which external factors functions of the kidney. -
The Title of the Article
Mechanism-Anchored Profiling Derived from Epigenetic Networks Predicts Outcome in Acute Lymphoblastic Leukemia Xinan Yang, PhD1, Yong Huang, MD1, James L Chen, MD1, Jianming Xie, MSc2, Xiao Sun, PhD2, Yves A Lussier, MD1,3,4§ 1Center for Biomedical Informatics and Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637 USA 2State Key Laboratory of Bioelectronics, Southeast University, 210096 Nanjing, P.R.China 3The University of Chicago Cancer Research Center, and The Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637 USA 4The Institute for Genomics and Systems Biology, and the Computational Institute, The University of Chicago, Chicago, IL 60637 USA §Corresponding author Email addresses: XY: [email protected] YH: [email protected] JC: [email protected] JX: [email protected] XS: [email protected] YL: [email protected] - 1 - Abstract Background Current outcome predictors based on “molecular profiling” rely on gene lists selected without consideration for their molecular mechanisms. This study was designed to demonstrate that we could learn about genes related to a specific mechanism and further use this knowledge to predict outcome in patients – a paradigm shift towards accurate “mechanism-anchored profiling”. We propose a novel algorithm, PGnet, which predicts a tripartite mechanism-anchored network associated to epigenetic regulation consisting of phenotypes, genes and mechanisms. Genes termed as GEMs in this network meet all of the following criteria: (i) they are co-expressed with genes known to be involved in the biological mechanism of interest, (ii) they are also differentially expressed between distinct phenotypes relevant to the study, and (iii) as a biomodule, genes correlate with both the mechanism and the phenotype. -
Association Between C4, C4A, and C4B Copy Number Variations And
www.nature.com/scientificreports OPEN Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune Received: 17 June 2016 Accepted: 04 January 2017 diseases: a meta-analysis Published: 16 February 2017 Na Li1, Jun Zhang2, Dan Liao2, Lu Yang2, Yingxiong Wang1 & Shengping Hou2,3 Although several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE. The complement system, which is involved in both innate and adaptive immunity, is characterized by triggered-enzyme cascades activated by alternative, lectin or classical pathways1. -
The Microtubule-Associated Protein MAPRE2 Is Involved in Perineural Invasion of Pancreatic Cancer Cells
1111-1116.qxd 8/9/2009 08:18 Ì ™ÂÏ›‰·1111 INTERNATIONAL JOURNAL OF ONCOLOGY 35: 1111-1116, 2009 The microtubule-associated protein MAPRE2 is involved in perineural invasion of pancreatic cancer cells IVANE ABIATARI1*, SONJA GILLEN1*, TIAGO DeOLIVEIRA1, THERESA KLOSE1, KONG BO1, NATHALIA A. GIESE2, HELMUT FRIESS1 and JÖRG KLEEFF1,3 1Department of General Surgery, Technische Universität München, Munich; 2Department of General Surgery, University of Heidelberg, Heidelberg, Germany; 3Center of Cancer Systems Biology, Department of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135-2997, USA Received May 4, 2009; Accepted July 10, 2009 DOI: 10.3892/ijo_00000426 Abstract. Perineural invasion of tumor cells is a characteristic Defining molecular mechanisms that allow pancreatic cancer feature of human pancreatic cancer. Unrevealing the molecular cells to grow along and into nerves is therefore important for mechanisms that enable cancer cells to invade and grow along the development of novel therapeutic strategies in pancreatic nerves is important for the development of novel therapeutic cancer, a disease whose incidence virtually mirrors its mortality strategies in this disease. We have previously identified tran- rate (5). We have previously identified and described in detail scriptional changes in highly nerve invasive pancreatic cancer the transcriptome signature of perineural invasion in pancreatic cells. Here we further analyzed one of the identified de- cancer by generating highly nerve invasive pancreatic cancer regulated genes, MAPRE2, a microtubule-associated protein. cells (6). One of the genes that displayed a significant up- MAPRE2 expression was significantly increased in high versus regulation in pancreatic cancer cells with a high potential for less nerve invasive pancreatic cancer cells, and changes of nerve invasion was MAPRE2. -
Examination of the Transcription Factors Acting in Bone Marrow
THESIS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY (PHD) Examination of the transcription factors acting in bone marrow derived macrophages by Gergely Nagy Supervisor: Dr. Endre Barta UNIVERSITY OF DEBRECEN DOCTORAL SCHOOL OF MOLECULAR CELL AND IMMUNE BIOLOGY DEBRECEN, 2016 Table of contents Table of contents ........................................................................................................................ 2 1. Introduction ............................................................................................................................ 5 1.1. Transcriptional regulation ................................................................................................... 5 1.1.1. Transcriptional initiation .................................................................................................. 5 1.1.2. Co-regulators and histone modifications .......................................................................... 8 1.2. Promoter and enhancer sequences guiding transcription factors ...................................... 11 1.2.1. General transcription factors .......................................................................................... 11 1.2.2. The ETS superfamily ..................................................................................................... 17 1.2.3. The AP-1 and CREB proteins ........................................................................................ 20 1.2.4. Other promoter specific transcription factor families ................................................... -
Table 2. Significant
Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S. -
Goat Anti-JAM2 / JAMB / CD322 Antibody Peptide-Affinity Purified Goat Antibody Catalog # Af1576a
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Goat Anti-JAM2 / JAMB / CD322 Antibody Peptide-affinity purified goat antibody Catalog # AF1576a Specification Goat Anti-JAM2 / JAMB / CD322 Antibody - Product Information Application WB Primary Accession P57087 Other Accession NP_067042, 58494, 67374 (mouse), 619374 (rat) Reactivity Human Predicted Mouse, Rat, Dog, Cow Host Goat Clonality Polyclonal Concentration 100ug/200ul Isotype IgG Calculated MW 33207 Goat Anti-JAM2 / JAMB / CD322 Antibody - AF1576a (0.5 µg/ml) staining of Human Additional Information Heart lysate (35 µg protein in RIPA buffer) with (B) and without (A) blocking with the Gene ID 58494 immunising peptide. Primary incubation was 1 hour. Detected by chemiluminescence. Other Names Junctional adhesion molecule B, JAM-B, Junctional adhesion molecule 2, JAM-2, Goat Anti-JAM2 / JAMB / CD322 Antibody - Vascular endothelial junction-associated Background molecule, VE-JAM, CD322, JAM2, C21orf43, VEJAM Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial Format cell sheets, forming continuous seals around 0.5 mg IgG/ml in Tris saline (20mM Tris cells and serving as a physical barrier to pH7.3, 150mM NaCl), 0.02% sodium azide, prevent solutes and water from passing freely with 0.5% bovine serum albumin through the paracellular space. The protein encoded by this immunoglobulin superfamily Storage gene member is localized in the tight junctions Maintain refrigerated at 2-8°C for up to 6 between high endothelial cells. It acts as an months. For long term storage store at adhesive ligand for interacting with a variety of -20°C in small aliquots to prevent immune cell types and may play a role in freeze-thaw cycles. -
Supplementary Information Integrative Analyses of Splicing in the Aging Brain: Role in Susceptibility to Alzheimer’S Disease
Supplementary Information Integrative analyses of splicing in the aging brain: role in susceptibility to Alzheimer’s Disease Contents 1. Supplementary Notes 1.1. Religious Orders Study and Memory and Aging Project 1.2. Mount Sinai Brain Bank Alzheimer’s Disease 1.3. CommonMind Consortium 1.4. Data Availability 2. Supplementary Tables 3. Supplementary Figures Note: Supplementary Tables are provided as separate Excel files. 1. Supplementary Notes 1.1. Religious Orders Study and Memory and Aging Project Gene expression data1. Gene expression data were generated using RNA- sequencing from Dorsolateral Prefrontal Cortex (DLPFC) of 540 individuals, at an average sequence depth of 90M reads. Detailed description of data generation and processing was previously described2 (Mostafavi, Gaiteri et al., under review). Samples were submitted to the Broad Institute’s Genomics Platform for transcriptome analysis following the dUTP protocol with Poly(A) selection developed by Levin and colleagues3. All samples were chosen to pass two initial quality filters: RNA integrity (RIN) score >5 and quantity threshold of 5 ug (and were selected from a larger set of 724 samples). Sequencing was performed on the Illumina HiSeq with 101bp paired-end reads and achieved coverage of 150M reads of the first 12 samples. These 12 samples will serve as a deep coverage reference and included 2 males and 2 females of nonimpaired, mild cognitive impaired, and Alzheimer's cases. The remaining samples were sequenced with target coverage of 50M reads; the mean coverage for the samples passing QC is 95 million reads (median 90 million reads). The libraries were constructed and pooled according to the RIN scores such that similar RIN scores would be pooled together. -
WO 2016/147053 Al 22 September 2016 (22.09.2016) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/147053 Al 22 September 2016 (22.09.2016) P O P C T (51) International Patent Classification: (71) Applicant: RESVERLOGIX CORP. [CA/CA]; 300, A61K 31/551 (2006.01) A61P 37/02 (2006.01) 4820 Richard Road Sw, Calgary, AB, T3E 6L1 (CA). A61K 31/517 (2006.01) C07D 239/91 (2006.01) (72) Inventors: WASIAK, Sylwia; 431 Whispering Water (21) International Application Number: Trail, Calgary, AB, T3Z 3V1 (CA). KULIKOWSKI, PCT/IB20 16/000443 Ewelina, B.; 31100 Swift Creek Terrace, Calgary, AB, T3Z 0B7 (CA). HALLIDAY, Christopher, R.A.; 403 (22) International Filing Date: 138-18th Avenue SE, Calgary, AB, T2G 5P9 (CA). GIL- 10 March 2016 (10.03.2016) HAM, Dean; 249 Scenic View Close NW, Calgary, AB, (25) Filing Language: English T3L 1Y5 (CA). (26) Publication Language: English (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 62/132,572 13 March 2015 (13.03.2015) US BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 62/264,768 8 December 2015 (08. 12.2015) US DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, [Continued on nextpage] (54) Title: COMPOSITIONS AND THERAPEUTIC METHODS FOR THE TREATMENT OF COMPLEMENT-ASSOCIATED DISEASES (57) Abstract: The invention comprises methods of modulating the complement cascade in a mammal and for treating and/or preventing diseases and disorders as sociated with the complement pathway by administering a compound of Formula I or Formula II, such as, for example, 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)- 5,7-dimethoxyquinazolin-4(3H)-one or a pharmaceutically acceptable salt thereof. -
The Atypical Guanine-Nucleotide Exchange Factor, Dock7, Negatively Regulates Schwann Cell Differentiation and Myelination
The Journal of Neuroscience, August 31, 2011 • 31(35):12579–12592 • 12579 Cellular/Molecular The Atypical Guanine-Nucleotide Exchange Factor, Dock7, Negatively Regulates Schwann Cell Differentiation and Myelination Junji Yamauchi,1,3,5 Yuki Miyamoto,1 Hajime Hamasaki,1,3 Atsushi Sanbe,1 Shinji Kusakawa,1 Akane Nakamura,2 Hideki Tsumura,2 Masahiro Maeda,4 Noriko Nemoto,6 Katsumasa Kawahara,5 Tomohiro Torii,1 and Akito Tanoue1 1Department of Pharmacology and 2Laboratory Animal Resource Facility, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan, 3Department of Biological Sciences, Tokyo Institute of Technology, Midori, Yokohama 226-8501, Japan, 4IBL, Ltd., Fujioka, Gumma 375-0005, Japan, and 5Department of Physiology and 6Bioimaging Research Center, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan In development of the peripheral nervous system, Schwann cells proliferate, migrate, and ultimately differentiate to form myelin sheath. In all of the myelination stages, Schwann cells continuously undergo morphological changes; however, little is known about their underlying molecular mechanisms. We previously cloned the dock7 gene encoding the atypical Rho family guanine-nucleotide exchange factor (GEF) and reported the positive role of Dock7, the target Rho GTPases Rac/Cdc42, and the downstream c-Jun N-terminal kinase in Schwann cell migration (Yamauchi et al., 2008). We investigated the role of Dock7 in Schwann cell differentiation and myelination. Knockdown of Dock7 by the specific small interfering (si)RNA in primary Schwann cells promotes dibutyryl cAMP-induced morpholog- ical differentiation, indicating the negative role of Dock7 in Schwann cell differentiation. It also results in a shorter duration of activation of Rac/Cdc42 and JNK, which is the negative regulator of myelination, and the earlier activation of Rho and Rho-kinase, which is the positive regulator of myelination.