ADDITIONAL MATERIALS AVAILABLE on the HEI WEBSITE Understanding the Functional Impact of VOC–Ozone Mixtures on the Chemistry
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Extensive Translation of Circular Rnas Driven by N6-Methyladenosine
Cell Research (2017) 27:626-641. ORIGINAL ARTICLE www.nature.com/cr Extensive translation of circular RNAs driven by N6-methyladenosine Yun Yang1, 2, 3, 4, *, Xiaojuan Fan2, *, Miaowei Mao4, 5, *, Xiaowei Song2, 4, Ping Wu6, 7, Yang Zhang8, Yongfeng Jin1, Yi Yang5, Ling-Ling Chen8, Yang Wang9, Catherine CL Wong6, 7, Xinshu Xiao3, Zefeng Wang2, 4 1Institute of Biochemistry, College of Life Sciences, Zhejiang University at Zijingang, Zhejiang, Hangzhou, Zhejiang 310058, Chi- na; 2CAS Key Lab for Computational Biology, CAS Center for Excellence in Molecular Cell Science, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 3Department of Integrative Biology and Physiology and the Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; 4Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 5Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Sci- ence and Technology, Shanghai, China; 6National Center for Protein Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 7Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai 201204, China; 8Institute of Biochemistry and Cell Biology, Shanghai Institute for Biolog- ical Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 9Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, China Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N6-methyladenosine (m6A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from cir- cRNAs in human cells. -
In Vivo Studies Using the Classical Mouse Diversity Panel
The Mouse Diversity Panel Predicts Clinical Drug Toxicity Risk Where Classical Models Fail Alison Harrill, Ph.D The Hamner-UNC Institute for Drug Safety Sciences 0 The Importance of Predicting Clinical Adverse Drug Reactions (ADR) Figure: Cath O’Driscoll Nature Publishing 2004 Risk ID PGx Testing 1 People Respond Differently to Drugs Pharmacogenetic Markers Identified by Genome-Wide Association Drug Adverse Drug Risk Allele Reaction (ADR) Abacavir Hypersensitivity HLA-B*5701 Flucloxacillin Hepatotoxicity Allopurinol Cutaneous ADR HLA-B*5801 Carbamazepine Stevens-Johnson HLA-B*1502 Syndrome Augmentin Hepatotoxicity DRB1*1501 Ximelagatran Hepatotoxicity DRB1*0701 Ticlopidine Hepatotoxicity HLA-A*3303 Average preclinical populations and human hepatocytes lack the diversity to detect incidence of adverse events that occur only in 1/10,000 people. Current Rodent Models of Risk Assessment The Challenge “At a time of extraordinary scientific progress, methods have hardly changed in several decades ([FDA] 2004)… Toxicologists face a major challenge in the twenty-first century. They need to embrace the new “omics” techniques and ensure that they are using the most appropriate animals if their discipline is to become a more effective tool in drug development.” -Dr. Michael Festing Quantitative geneticist Toxicol Pathol. 2010;38(5):681-90 Rodent Models as a Strategy for Hazard Characterization and Pharmacogenetics Genetically defined rodent models may provide ability to: 1. Improve preclinical prediction of drugs that carry a human safety risk 2. -
Composition of Herpesvirus Ribonucleoprotein Complexes †
Abstract Composition of Herpesvirus Ribonucleoprotein Complexes † Eric S. Pringle 1,2,* and Craig McCormick 1,2 1 Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada; [email protected] 2 Beatrice Hunter Cancer Research Institute, Halifax, NS B3H 4R2, Canada * Correspondence: [email protected] † Presented at Viruses 2020—Novel Concepts in Virology, Barcelona, Spain, 5–7 February 2020. Published: 4 July 2020 Abstract: Herpesvirus genomes are decoded by host RNA polymerase enzymes, generating messenger ribonucleotides (mRNA) that are post-transcriptionally modified and exported to the cytoplasm through the combined work of host and viral factors. These viral mRNA bear 5′-m7GTP caps and poly(A) tails that should permit the assembly of canonical host eIF4F cap-binding complexes to initiate protein synthesis. However, the precise mechanisms of translation initiation remain to be investigated for Kaposi’s sarcoma-associated herpesvirus (KSHV) and other herpesviruses. During KSHV lytic replication in lymphoid cells, the activation of caspases leads to the cleavage of eIF4G and depletion of eIF4F. Translating mRNPs depleted of eIF4F retain viral mRNA, suggesting that non-eIF4F translation initiation is sufficient to support viral protein synthesis. To identify proteins required to support viral protein synthesis, we isolated and characterized actively translating messenger ribonucleoprotein (mRNP) complexes by ultracentrifugation and sucrose-gradient fractionation followed by quantitative mass spectrometry. The abundance of host translation initiation factors available to initiate viral protein synthesis were comparable between cells undergoing KSHV lytic or latent replication. The translation initiation factors eIF4E2, NCBP1, eIF4G2, and eIF3d were detected in association with actively translating mRNP complexes during KSHV lytic replication, but their depletion by RNA silencing did not affect virion production. -
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
Hippo Signaling in Cancer: Lessons from Drosophila Models
fcell-07-00085 May 22, 2019 Time: 18:12 # 1 REVIEW published: 24 May 2019 doi: 10.3389/fcell.2019.00085 Hippo Signaling in Cancer: Lessons From Drosophila Models Kirti Snigdha1, Karishma Sanjay Gangwani1, Gauri Vijay Lapalikar2, Amit Singh1,3,4,5 and Madhuri Kango-Singh1,3,4,5* 1 Department of Biology, University of Dayton, Dayton, OH, United States, 2 Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, United States, 3 Pre-Medical Programs, University of Dayton, Dayton, OH, United States, 4 Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton, OH, United States, 5 Integrated Science and Engineering Center, University of Dayton, Dayton, OH, United States Hippo pathway was initially identified through genetic screens for genes regulating organ size in fruitflies. Recent studies have highlighted the role of Hippo signaling as a key regulator of homeostasis, and in tumorigenesis. Hippo pathway is comprised of genes that act as tumor suppressor genes like hippo (hpo) and warts (wts), and oncogenes like yorkie (yki). YAP and TAZ are two related mammalian homologs of Drosophila Yki that act as effectors of the Hippo pathway. Hippo signaling deficiency can cause Edited by: YAP- or TAZ-dependent oncogene addiction for cancer cells. YAP and TAZ are often SrinivasVinod Saladi, activated in human malignant cancers. These transcriptional regulators may initiate Harvard Medical School, tumorigenic changes in solid tumors by inducing cancer stem cells and proliferation, United States culminating in metastasis and chemo-resistance. Given the complex mechanisms (e.g., Reviewed by: Sirisha M. Cheedipudi, of the cancer microenvironment, and the extrinsic and intrinsic cues) that overpower University of Texas Health Science YAP/TAZ inhibition, the molecular roles of the Hippo pathway in tumor growth and Center at Houston, United States Rizaldy Paz Scott, progression remain poorly defined. -
EIF4G2 Rabbit Pab
Leader in Biomolecular Solutions for Life Science EIF4G2 Rabbit pAb Catalog No.: A2897 Basic Information Background Catalog No. Translation initiation is mediated by specific recognition of the cap structure by A2897 eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by this gene Observed MW shares similarity with the C-terminal region of eIF4G that contains the binding sites for 102kDa eIF4A and eIF3; eIF4G, in addition, contains a binding site for eIF4E at the N-terminus. Unlike eIF4G, which supports cap-dependent and independent translation, this gene Calculated MW product functions as a general repressor of translation by forming translationally 98kDa/102kDa inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants Category encoding different isoforms of this gene have been described. Primary antibody Applications WB, IHC, IF, IP Cross-Reactivity Human, Mouse, Rat Recommended Dilutions Immunogen Information WB 1:500 - 1:1000 Gene ID Swiss Prot 1982 P78344 IHC 1:100 - 1:200 Immunogen 1:50 - 1:200 IF A synthetic peptide corresponding to a sequence within amino acids 750-850 of human EIF4G2 (NP_001409.3). IP 1:50 - 1:200 Synonyms EIF4G2;AAG1;DAP5;NAT1;P97 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using EIF4G2 antibody (A2897) at 1:400 dilution. -
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. -
Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS
Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen, -
Robust Heat Shock Induces Eif2α-Phosphorylation
2078 Research Article Robust heat shock induces eIF2α-phosphorylation- independent assembly of stress granules containing eIF3 and 40S ribosomal subunits in budding yeast, Saccharomyces cerevisiae Tomás Grousl1, Pavel Ivanov1,*, Ivana Frydlová1, Pavla Vasicová1, Filip Janda1, Jana Vojtová1, Katerina Malínská1, Ivana Malcová1, Lenka Nováková1, Dana Janosková1, Leos Valásek2 and Jirí Hasek1,‡ 1Laboratory of Cell Reproduction, Institute of Microbiology of the AS CR, v.v.i., Prague, Czech Republic 2Laboratory of Regulation of Gene Expression, Institute of Microbiology of the AS CR, v.v.i., Prague, Czech Republic *Present address: A.N. Belozersky Institute of Physico-Chemical Biology MSU, Moscow, Russia ‡Author for correspondence (e-mail: [email protected]) Accepted 18 March 2009 Journal of Cell Science 122, 2078-2088 Published by The Company of Biologists 2009 doi:10.1242/jcs.045104 Summary Environmental stresses inducing translation arrest are markers also colocalized with eIF3a. Microscopic analyses of accompanied by the deposition of translational components into the edc3Δlsm4ΔC mutant demonstrated that different stress granules (SGs) serving as mRNA triage sites. It has scaffolding proteins are required to induce SGs upon robust recently been reported that, in Saccharomyces cerevisiae, heat shock as opposed to glucose deprivation. Even though formation of SGs occurs as a result of a prolonged glucose eIF2α became phosphorylated under these stress conditions, the starvation. However, these SGs did not contain eIF3, one of decrease in polysomes and formation of SGs occurred hallmarks of mammalian SGs. We have analyzed the effect of independently of phosphorylation of eIF2α. We conclude that robust heat shock on distribution of eIF3a/Tif32p/Rpg1p and under specific stress conditions, such as robust heat shock, yeast showed that it results in the formation of eIF3a accumulations SGs do contain eIF3 and 40S ribosomes and utilize alternative containing other eIF3 subunits, known yeast SG components routes for their assembly. -
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Yildiz et al. Neural Development (2019) 14:5 https://doi.org/10.1186/s13064-019-0129-x RESEARCH ARTICLE Open Access Zebrafish prdm12b acts independently of nkx6.1 repression to promote eng1b expression in the neural tube p1 domain Ozge Yildiz1, Gerald B. Downes2 and Charles G. Sagerström1* Abstract Background: Functioning of the adult nervous system depends on the establishment of neural circuits during embryogenesis. In vertebrates, neurons that make up motor circuits form in distinct domains along the dorsoventral axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear. Methods: We used CRISPR/Cas9 to generate the first germline mutants for prdm12 and employed this resource, together with classical luciferase reporter assays and co-immunoprecipitation experiments, to study prdm12b function in zebrafish. We also generated germline mutants for bhlhe22 and nkx6.1 to examine how these TFs act with prdm12b to control p1 formation. Results: We find that prdm12b mutants lack eng1b expression in the p1 domain and also possess an abnormal touch-evoked escape response. Using luciferase reporter assays, we demonstrate that Prdm12b acts as a transcriptional repressor. We also show that the Bhlhe22 TF binds via the Prdm12b zinc finger domain to form a complex. However, bhlhe22 mutants display normal eng1b expression in the p1 domain. While prdm12 has been proposed to promote p1 fates by repressing expression of the nkx6.1 TF, we do not observe an expansion of the nkx6.1 domain upon loss of prdm12b function, nor is eng1b expression restored upon simultaneous loss of prdm12b and nkx6.1. -
Early Alterations of RNA Metabolism and Splicing from Adult Corticospinal Neurons In
bioRxiv preprint doi: https://doi.org/10.1101/667733; this version posted June 12, 2019. 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. 1 Early alterations of RNA metabolism and splicing from adult corticospinal neurons in 2 an ALS mouse model 3 4 Christine Marques1,2, Mathieu Fischer1,3, Céline Keime4, Thibaut Burg1, Aurore Brunet1, 5 Jelena Scekic-Zahirovic1 & Caroline Rouaux1* 6 7 8 9 1Inserm UMR_S 1118, Mécanismes centraux et périphériques de la neurodégénérescence, 10 Faculté de Médecine, Université de Strasbourg, Strasbourg, France. 11 2Current address: Department of Neurobiology, Harvard Medical School, Boston, MA, USA; 12 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 13 3Current address: Department of Paediatrics, John Radcliffe Hospital, University of Oxford, 14 Oxford, UK. 15 4Inserm UMR_S 1258, CRNS UMR_S 7104, Université de Strasbourg, IGBMC, Strasbourg, 16 France. 17 18 *Correspondence should be addressed to: C.R. ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/667733; this version posted June 12, 2019. 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 Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease clinically defined as the combined degeneration of corticospinal and corticobulbar neurons (CSN), and bulbar and spinal motor neurons (MN). A growing body of evidence points to the motor cortex, where CSN are located, as the potential initiation site of ALS. However, little is known about the spatiotemporal dynamics of CSN degeneration and the molecular pathways involved. -
Landscape of Tumor Suppressor Long Noncoding Rnas in Breast Cancer Boran Pang1, Qin Wang2, Shipeng Ning2, Junqiang Wu2, Xingda Zhang2, Yanbo Chen2 and Shouping Xu2*
Pang et al. Journal of Experimental & Clinical Cancer Research (2019) 38:79 https://doi.org/10.1186/s13046-019-1096-0 RESEARCH Open Access Landscape of tumor suppressor long noncoding RNAs in breast cancer Boran Pang1, Qin Wang2, Shipeng Ning2, Junqiang Wu2, Xingda Zhang2, Yanbo Chen2 and Shouping Xu2* Abstract Background: The landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown. Methods: Data from whole transcriptome sequencing of 33 breast specimens in the Harbin Medical University Cancer Center cohort and The Cancer Genome Atlas was applied to identify and validate the landscape of tumor suppressor long noncoding RNAs, which was further validated by The Cancer Genome Atlas pancancer data including 33 cancer types and 12,839 patients. Next, the expression model, prognostic roles, potential biological functions and epigenetic regulation of tumor suppressor long noncoding RNAs were investigated and validated in the breast cancer and pancancer cohorts. Finally, EPB41L4A-AS2 was selected to validate our novel finding, and the tumor suppressive roles of EPB41L4A-AS2 in breast cancer were examined. Results: We identified and validated the landscape of tumor suppressor long noncoding RNAs in breast cancer. The expression of the identified long noncoding RNAs was downregulated in cancer tissue samples compared with normal tissue samples, and these long noncoding RNAs correlated with a favorable prognosis in breast cancer patients and the patients in the pancancer cohort. Multiple carcinogenesis-associated biological functions were predicted to be regulated negatively by these long noncoding RNAs. Moreover, these long noncoding RNAs were transcriptionally regulated by epigenetic modification, including DNA methylation and histone methylation modification.