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FK506-Binding Protein 12.6/1B, a Negative Regulator of [Ca2+], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats
This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. A link to any extended data will be provided when the final version is posted online. Research Articles: Neurobiology of Disease FK506-Binding Protein 12.6/1b, a negative regulator of [Ca2+], rescues memory and restores genomic regulation in the hippocampus of aging rats John C. Gant1, Eric M. Blalock1, Kuey-Chu Chen1, Inga Kadish2, Olivier Thibault1, Nada M. Porter1 and Philip W. Landfield1 1Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY 40536 2Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 DOI: 10.1523/JNEUROSCI.2234-17.2017 Received: 7 August 2017 Revised: 10 October 2017 Accepted: 24 November 2017 Published: 18 December 2017 Author contributions: J.C.G. and P.W.L. designed research; J.C.G., E.M.B., K.-c.C., and I.K. performed research; J.C.G., E.M.B., K.-c.C., I.K., and P.W.L. analyzed data; J.C.G., E.M.B., O.T., N.M.P., and P.W.L. wrote the paper. Conflict of Interest: The authors declare no competing financial interests. NIH grants AG004542, AG033649, AG052050, AG037868 and McAlpine Foundation for Neuroscience Research Corresponding author: Philip W. Landfield, [email protected], Department of Pharmacology & Nutritional Sciences, University of Kentucky, 800 Rose Street, UKMC MS 307, Lexington, KY 40536 Cite as: J. Neurosci ; 10.1523/JNEUROSCI.2234-17.2017 Alerts: Sign up at www.jneurosci.org/cgi/alerts to receive customized email alerts when the fully formatted version of this article is published. -
Mrna-Lncrna Co-Expression Network Analysis Reveals the Role of Lncrnas in Immune Dysfunction During Severe SARS-Cov-2 Infection
viruses Article mRNA-lncRNA Co-Expression Network Analysis Reveals the Role of lncRNAs in Immune Dysfunction during Severe SARS-CoV-2 Infection Sumit Mukherjee 1 , Bodhisattwa Banerjee 2 , David Karasik 2 and Milana Frenkel-Morgenstern 1,* 1 Cancer Genomics and BioComputing of Complex Diseases Lab, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; [email protected] 2 Musculoskeletal Genetics Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; [email protected] (B.B.); [email protected] (D.K.) * Correspondence: [email protected]; Tel.: +972-72-264-4901 Abstract: The recently emerged SARS-CoV-2 virus is responsible for the ongoing COVID-19 pan- demic that has rapidly developed into a global public health threat. Patients severely affected with COVID-19 present distinct clinical features, including acute respiratory disorder, neutrophilia, cy- tokine storm, and sepsis. In addition, multiple pro-inflammatory cytokines are found in the plasma of such patients. Transcriptome sequencing of different specimens obtained from patients suffering from severe episodes of COVID-19 shows dynamics in terms of their immune responses. However, those host factors required for SARS-CoV-2 propagation and the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive. In the present study, we analyzed the mRNA-long non-coding RNA (lncRNA) co-expression network derived from publicly available SARS-CoV-2-infected transcriptome data of human lung epithelial Citation: Mukherjee, S.; Banerjee, B.; cell lines and bronchoalveolar lavage fluid (BALF) from COVID-19 patients. Through co-expression Karasik, D.; Frenkel-Morgenstern, M. -
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. -
Long Non-Coding RNA EGOT Promotes the Malignant Phenotypes of Hepatocellular Carcinoma Cells and Increases the Expression of HMGA2 Via Down-Regulating Mir-33A-5P
OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Long Non-Coding RNA EGOT Promotes the Malignant Phenotypes of Hepatocellular Carcinoma Cells and Increases the Expression of HMGA2 via Down-Regulating miR-33a-5p This article was published in the following Dove Press journal: OncoTargets and Therapy Shimin Wu 1 Background: Chronic hepatitis C virus (HCV) infection is an important risk factor for hepato- Hongwu Ai2 cellular carcinoma (HCC). EGOT is a long non-coding RNA (lncRNA) induced after HCV Kehui Zhang3,4 infection that increases viral replication by antagonizing the antiviral response. Interestingly, Hao Yun3,4 EGOTalso acts as a crucial regulator in multiple cancers. However, its role in HCC remains unclear. Fei Xie3,4 Methods: Real-time PCR (RT-PCR) was used to detect the expression of EGOT in HCC samples and cell lines. CCK-8 assay and colony formation assay were performed to evaluate 1 Center for Clinical Laboratory, General the effect of EGOT on proliferation. Scratch healing assay and transwell assay were used to Hospital of the Yangtze River Shipping, Wuhan Brain Hospital, Wuhan 430030, detect the changes of migration and invasion. Flow cytometry was used to detect the effect of People’s Republic of China; 2Center for EGOT on apoptosis. Interaction between EGOT and miR-33a-5p was determined by bioin- Clinical Laboratory, Wuhan Kangjian formatics analysis, RT-PCR, and dual-luciferase reporter assay. Western blot was used to Maternal and Infant Hospital, Wuhan 430050, People’s Republic of China; confirm that high mobility group protein A2 (HMGA2) could be modulated by EGOT. -
The Small G Protein Arl8 Contributes to Lysosomal Function and Long-Range Axonal Transport in Drosophila
This is a repository copy of The small G protein Arl8 contributes to lysosomal function and long-range axonal transport in Drosophila. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/134948/ Version: Accepted Version Article: Rosa-Ferreira, Cláudia, Sweeney, Sean orcid.org/0000-0003-2673-9578 and Munro, Sean (Accepted: 2018) The small G protein Arl8 contributes to lysosomal function and long- range axonal transport in Drosophila. Biology Open. (In Press) https://doi.org/10.1242/bio.035964 Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ The small G protein Arl8 contributes to lysosomal function and long-range axonal transport in Drosophila Cláudia Rosa-Ferreira1 , Sean T. Sweeney2 and Sean Munro1* 1: MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge CB2 0QH UK 2: Department of Biology University of York York YO10 5DD UK *: Corresponding author. Email: [email protected] © 2018. -
Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A. -
Coding RNA Genes
Review A guide to naming human non-coding RNA genes Ruth L Seal1,2,* , Ling-Ling Chen3, Sam Griffiths-Jones4, Todd M Lowe5, Michael B Mathews6, Dawn O’Reilly7, Andrew J Pierce8, Peter F Stadler9,10,11,12,13, Igor Ulitsky14 , Sandra L Wolin15 & Elspeth A Bruford1,2 Abstract working on non-coding RNA (ncRNA) nomenclature in the mid- 1980s with the approval of initial gene symbols for mitochondrial Research on non-coding RNA (ncRNA) is a rapidly expanding field. transfer RNA (tRNA) genes. Since then, we have worked closely Providing an official gene symbol and name to ncRNA genes brings with experts in the ncRNA field to develop symbols for many dif- order to otherwise potential chaos as it allows unambiguous ferent kinds of ncRNA genes. communication about each gene. The HUGO Gene Nomenclature The number of genes that the HGNC has named per ncRNA class Committee (HGNC, www.genenames.org) is the only group with is shown in Fig 1, and ranges in number from over 4,500 long the authority to approve symbols for human genes. The HGNC ncRNA (lncRNA) genes and over 1,900 microRNA genes, to just four works with specialist advisors for different classes of ncRNA to genes in the vault and Y RNA classes. Every gene symbol has a ensure that ncRNA nomenclature is accurate and informative, Symbol Report on our website, www.genenames.org, which where possible. Here, we review each major class of ncRNA that is displays the gene symbol, gene name, chromosomal location and currently annotated in the human genome and describe how each also includes links to key resources such as Ensembl (Zerbino et al, class is assigned a standardised nomenclature. -
A Yeast Phenomic Model for the Influence of Warburg Metabolism on Genetic Buffering of Doxorubicin Sean M
Santos and Hartman Cancer & Metabolism (2019) 7:9 https://doi.org/10.1186/s40170-019-0201-3 RESEARCH Open Access A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin Sean M. Santos and John L. Hartman IV* Abstract Background: The influence of the Warburg phenomenon on chemotherapy response is unknown. Saccharomyces cerevisiae mimics the Warburg effect, repressing respiration in the presence of adequate glucose. Yeast phenomic experiments were conducted to assess potential influences of Warburg metabolism on gene-drug interaction underlying the cellular response to doxorubicin. Homologous genes from yeast phenomic and cancer pharmacogenomics data were analyzed to infer evolutionary conservation of gene-drug interaction and predict therapeutic relevance. Methods: Cell proliferation phenotypes (CPPs) of the yeast gene knockout/knockdown library were measured by quantitative high-throughput cell array phenotyping (Q-HTCP), treating with escalating doxorubicin concentrations under conditions of respiratory or glycolytic metabolism. Doxorubicin-gene interaction was quantified by departure of CPPs observed for the doxorubicin-treated mutant strain from that expected based on an interaction model. Recursive expectation-maximization clustering (REMc) and Gene Ontology (GO)-based analyses of interactions identified functional biological modules that differentially buffer or promote doxorubicin cytotoxicity with respect to Warburg metabolism. Yeast phenomic and cancer pharmacogenomics data were integrated to predict differential gene expression causally influencing doxorubicin anti-tumor efficacy. Results: Yeast compromised for genes functioning in chromatin organization, and several other cellular processes are more resistant to doxorubicin under glycolytic conditions. Thus, the Warburg transition appears to alleviate requirements for cellular functions that buffer doxorubicin cytotoxicity in a respiratory context. -
Anti-ARL8B Antibody (ARG43276)
Product datasheet [email protected] ARG43276 Package: 50 μg anti-ARL8B antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes ARL8B Tested Reactivity Hu, Ms Tested Application IHC-P, WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name ARL8B Antigen Species Human Immunogen Recombinant protein corresponding to aa. 20-186 of Human ARL8B. Conjugation Un-conjugated Alternate Names Novel small G protein indispensable for equal chromosome segregation 1; ARL10C; ADP-ribosylation factor-like protein 8B; Gie1; ADP-ribosylation factor-like protein 10C Application Instructions Application table Application Dilution IHC-P 1:100 WB 4 µg/ml Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control Mouse brain, NIH/3T3 and Jurkat Calculated Mw 22 kDa Observed Size ~ 22 kDa Properties Form Liquid Purification Caprylic acid ammonium sulfate precipitation purified. Buffer 0.01 M PBS (pH 7.4), 0.03% Proclin 300 and 50% Glycerol. Preservative 0.03% Proclin 300 Stabilizer 50% Glycerol Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. www.arigobio.com 1/2 Note For laboratory research only, not for drug, diagnostic or other use. Bioinformation Gene Symbol ARL8B Gene Full Name ADP-ribosylation factor-like 8B Function Plays a role in lysosome motility (PubMed:16537643, PubMed:25898167). -
Hippo and Sonic Hedgehog Signalling Pathway Modulation of Human Urothelial Tissue Homeostasis
Hippo and Sonic Hedgehog signalling pathway modulation of human urothelial tissue homeostasis Thomas Crighton PhD University of York Department of Biology November 2020 Abstract The urinary tract is lined by a barrier-forming, mitotically-quiescent urothelium, which retains the ability to regenerate following injury. Regulation of tissue homeostasis by Hippo and Sonic Hedgehog signalling has previously been implicated in various mammalian epithelia, but limited evidence exists as to their role in adult human urothelial physiology. Focussing on the Hippo pathway, the aims of this thesis were to characterise expression of said pathways in urothelium, determine what role the pathways have in regulating urothelial phenotype, and investigate whether the pathways are implicated in muscle-invasive bladder cancer (MIBC). These aims were assessed using a cell culture paradigm of Normal Human Urothelial (NHU) cells that can be manipulated in vitro to represent different differentiated phenotypes, alongside MIBC cell lines and The Cancer Genome Atlas resource. Transcriptomic analysis of NHU cells identified a significant induction of VGLL1, a poorly understood regulator of Hippo signalling, in differentiated cells. Activation of upstream transcription factors PPARγ and GATA3 and/or blockade of active EGFR/RAS/RAF/MEK/ERK signalling were identified as mechanisms which induce VGLL1 expression in NHU cells. Ectopic overexpression of VGLL1 in undifferentiated NHU cells and MIBC cell line T24 resulted in significantly reduced proliferation. Conversely, knockdown of VGLL1 in differentiated NHU cells significantly reduced barrier tightness in an unwounded state, while inhibiting regeneration and increasing cell cycle activation in scratch-wounded cultures. A signalling pathway previously observed to be inhibited by VGLL1 function, YAP/TAZ, was unaffected by VGLL1 manipulation. -
Transcriptional Profiling of Long Non-Coding Rnas and Novel
Brunner et al. Genome Biology 2012, 13:R75 http://genomebiology.com/2012/13/8/R75 RESEARCH Open Access Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers Alayne L Brunner1, Andrew H Beck1,2, Badreddin Edris1,3, Robert T Sweeney1, Shirley X Zhu1, Rui Li1, Kelli Montgomery1, Sushama Varma1, Thea Gilks1, Xiangqian Guo1, Joseph W Foley3, Daniela M Witten4, Craig P Giacomini1,5, Ryan A Flynn6, Jonathan R Pollack1, Robert Tibshirani7,8, Howard Y Chang6, Matt van de Rijn1 and Robert B West1* Abstract Background: Molecular characterization of tumors has been critical for identifying important genes in cancer biology and for improving tumor classification and diagnosis. Long non-coding RNAs, as a new, relatively unstudied class of transcripts, provide a rich opportunity to identify both functional drivers and cancer-type-specific biomarkers. However, despite the potential importance of long non-coding RNAs to the cancer field, no comprehensive survey of long non-coding RNA expression across various cancers has been reported. Results: We performed a sequencing-based transcriptional survey of both known long non-coding RNAs and novel intergenic transcripts across a panel of 64 archival tumor samples comprising 17 diagnostic subtypes of adenocarcinomas, squamous cell carcinomas and sarcomas. We identified hundreds of transcripts from among the known 1,065 long non-coding RNAs surveyed that showed variability in transcript levels between the tumor types and are therefore potential biomarker candidates. We discovered 1,071 novel intergenic transcribed regions and demonstrate that these show similar patterns of variability between tumor types. -
ARL8B Sirna (M): Sc-141251
SAN TA C RUZ BI OTEC HNOL OG Y, INC . ARL8B siRNA (m): sc-141251 BACKGROUND STORAGE AND RESUSPENSION ADP-ribosylation factors (ARFs) are highly conserved guanine nucleotide bind - Store lyophilized siRNA duplex at -20° C with desiccant. Stable for at least ing proteins that enhance the ADP-ribosyltransferase activity of Cholera Toxin. one year from the date of shipment. Once resuspended, store at -20° C, ARF’s are important in eukaryotic vesicular trafficking pathways and they play avoid contact with RNAses and repeated freeze thaw cycles. an essential role in the activation of phospholipase D (PC-PLD). ARL8B (ADP- Resuspend lyophilized siRNA duplex in 330 µl of the RNAse-free water ribosylation factor-like protein 8B), also known as ARL10C or GIE1, is a 186 pro vided. Resuspension of the siRNA duplex in 330 µl of RNAse-free water amino acid protein that localizes to the late endosome membrane and belongs makes a 10 µM solution in a 10 µM Tris-HCl, pH 8.0, 20 mM NaCl, 1 mM to the ARL family of ARF-like GTPase proteins. Expressed ubiquitously, ARL8A EDTA buffered solution. interacts with Tubulin and is thought to play a role in lysosome motility, as well as in chromosomal segregation. The gene encoding ARL8B maps to APPLICATIONS human chromosome 3, which houses over 1,100 genes, including a chemokine receptor (CKR) gene cluster and a variety of human cancer-related gene loci. ARL8B siRNA (m) is recommended for the inhibition of ARL8B expression in mouse cells. REFERENCES SUPPORT REAGENTS 1. Secombe, J., et al. 2004.