DOCSLIB.ORG

Antisense Afp Transcripts in Mouse Liver and Their Potential Role in Afp Gene Regulation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antisense Afp Transcripts in Mouse Liver and Their Potential Role in Afp Gene Regulation University of Kentucky UKnowledge Theses and Dissertations--Microbiology, Microbiology, Immunology, and Molecular Immunology, and Molecular Genetics Genetics 2017 ANTISENSE AFP TRANSCRIPTS IN MOUSE LIVER AND THEIR POTENTIAL ROLE IN AFP GENE REGULATION Maria S. Dixon University of Kentucky, [email protected] Digital Object Identifier: https://doi.org/10.13023/ETD.2017.356 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Dixon, Maria S., "ANTISENSE AFP TRANSCRIPTS IN MOUSE LIVER AND THEIR POTENTIAL ROLE IN AFP GENE REGULATION" (2017). Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics. 14. https://uknowledge.uky.edu/microbio_etds/14 This Doctoral Dissertation is brought to you for free and open access by the Microbiology, Immunology, and Molecular Genetics at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless an embargo applies. I retain all other ownership rights to the copyright of my work. I also retain the right to use in future works (such as articles or books) all or part of my work. I understand that I am free to register the copyright to my work. REVIEW, APPROVAL AND ACCEPTANCE The document mentioned above has been reviewed and accepted by the student’s advisor, on behalf of the advisory committee, and by the Director of Graduate Studies (DGS), on behalf of the program; we verify that this is the final, approved version of the student’s thesis including all changes required by the advisory committee. The undersigned agree to abide by the statements above. Maria S. Dixon, Student Dr. Martha L. Peterson, Major Professor Dr. Ken Fields, Director of Graduate Studies ANTISENSE AFP TRANSCRIPTS IN MOUSE LIVER AND THEIR POTENTIAL ROLE IN AFP GENE REGULATION DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Medicine at the University of Kentucky By Maria S. Dixon Lexington, Kentucky Director: Dr. Martha L. Peterson, Professor of Microbiology, Immunology & Molecular Genetics Lexington, Kentucky 2017 Copyright © Maria S. Dixon 2017 ABSTRACT OF DISSERTATION ANTISENSE AFP TRANSCRIPTS IN MOUSE LIVER AND THEIR POTENTIAL ROLE IN AFP GENE REGULATION Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, ranking the sixth most common cancer and third most common cause of cancer mortality worldwide. Alpha-fetoprotein (AFP) is a plasma protein that is highly expressed in the fetal liver and shut off after birth. AFP expression is elevated in regenerating adult liver and HCC and has been used extensively as a diagnostic marker of liver cancer. We have been studying mouse liver gene regulation to better understand mechanisms by which changes in gene expression contribute to liver development, homeostasis and disease. Zinc Fingers and Homeoboxes 2 (Zhx2) has been identified as a repressor of AFP, but the mechanism of this regulation remains unknown. Interestingly, all targets of Zhx2 that have been identified to date, including H19, Glypican 3, Elovl3 and Cytochrome P450 (CYP) genes, are also known to be misregulated in HCC. Thus, a better understanding of the mechanism by which these genes are regulated by Zhx2 will likely lead to new insights into gene regulation during HCC progression. Antisense transcripts belong to a diverse class of long noncoding RNA molecules >200 nucleotides in length that often structurally resemble mRNAs, but do not encode proteins. While studying AFP mRNA regulation by Zhx2 in the mouse, our lab identified novel antisense AFP (asAFP) RNA transcripts that partially overlap the 3’ half of the mouse AFP gene. ENCODE tracks of ChIP-seq data for histone modifications in mouse liver show that the genomic region around the 5’ end of asAFP RNA has peaks for marks associated with promoters and enhancers. To better understand asAFP regulation, I identified the asAFP RNA 5’ end and the promoter elements that drive transcription. asAFP RNAs are ~5kb alternatively spliced, mainly cytoplasmic transcripts containing 2-4 exons. These transcripts were also detected in adult mouse liver RNA- seq data. asAFP is likely a noncoding RNA because it contains several small open reading frames that are 98 aa or smaller with no known functional domains or homology to known proteins. There is no evidence for similar transcripts in human liver. The abundance of asAFP RNA inversely correlates with AFP mRNA levels during postnatal liver development. Normally, asAFP RNA levels are high and AFP mRNA levels are low in the adult mouse liver. However, in the absence of Zhx2, AFP mRNA levels are higher and asAFP RNA levels are reduced, suggesting asAFP may be involved in the developmental regulation of AFP. Antisense transcripts function through a variety of mechanisms to positively or negatively regulate the expression of target genes. To explore the role of asAFP RNA in AFP gene regulation, I expressed segments of asAFP RNA in a mouse liver cell line and measured endogenous AFP mRNA levels. My data revealed that all segments of asAFP repressed endogenous AFP mRNA in trans. To determine the mechanism by which asAFP RNA regulates AFP, I expressed asAFP segments that overlapped only with exons or introns of AFP. The asAFP segments that overlap with the exons showed greater repression of endogenous AFP mRNA levels than those overlapping with intronic sequences. Additionally, I considered whether asAFP RNA repression of AFP mRNA may involve RNA editing by Adenosine deaminase acting on RNA (ADAR). ADARs convert adenosine to inosine in double-stranded RNAs that results in RNA degradation. My data indicate that AFP and asAFP dsRNA is not extensively edited, suggesting ADAR mediated decay is not involved in the regulation of AFP mRNA expression. However, further studies are required to determine the mechanism of cytoplasmic AFP mRNA degradation. Together, my data characterizes the transcriptional regulation of novel mouse asAFP transcripts and provides a model system to investigate how these transcripts regulate AFP mRNA through RNA-RNA interaction. KEYWORDS: Long Noncoding RNA, asAFP, AFP, RNA-RNA interaction, gene regulation Maria S. Dixon Student’s Signature Date ANTISENSE AFP TRANSCRIPTS IN MOUSE LIVER AND THEIR POTENTIAL ROLE IN AFP GENE REGULATION By Maria S. Dixon Martha L. Peterson Director of Dissertation Ken Fields Director of Graduate Studies Date I dedicate this dissertation to my loving husband. ACKNOWLEDGEMENTS “For I know the plans I have for you, declares the Lord,” Jeremiah 29:11. I give all thanks and praises to my Lord and Savior, Jesus Christ for guiding me throughout this journey. I would like to thank my mentor, Dr. Martha Peterson for your support and guidance through the most challenging years of my life. I am grateful to my committee members: Dr. Brett Spear, Dr. Brian Rymond and Dr. Subbarao Bondada for their guidance and feedback throughout my doctoral studies. Special thanks to Dr. John D’Orazio for not only serving as my external examiner, but for graciously allowing me to use his laboratory equipment for the completion of many of my experiments. I am truly grateful to Drs. Shirley Qiu, Jieyun Jiang and Lilia Turcios for their guidance, patience and expertise, which has molded me into the scientist that I am today. Special thanks to all the members of the Spear lab for your feedback during lab meetings and support. I would also like to thank the Microbiology, Immunology and Molecular Genetics department, Ms. Kate Fresca, and Dr. Beth Garvy for providing an amazing and supportive academic environment. My friends have been my “rams in the bush” and have given me unwavering support and love during the last five years. I am truly blessed to have such an amazing group of people in my life. Thank you, Cheavar Blair, LaQueta Shelton, Isabel Derera, Will Arnold, Katie Mckenna, Drs. Karine Oben, Sara Alhakeem, and Grant Jones. I am so proud of each of you and I am going to miss you dearly! To my mentees, Maya James and Brittany Rice, thank you for encouraging talks and motivating me to finish the course. I don’t know where I would be without my family. To my parents, Major and Bonnie Smith, thank you for your unconditional love, support, and guidance. To my grandmother, Viola Hughes, you have been a true inspiration in my life. Special thanks to my sister and cousin, Monique Smith and Deedra Hughes for being my best friends and angels on earth. To my Kentucky mother, Ms. Susan Jones, thank you for your love, prayers, and encouraging words. Lastly, I am extremely grateful to my loving husband, William L. Dixon III. You are truly my Miracle on earth! Thank you for being my biggest cheerleader and loving me through thick and thin; you have shown me the true meaning of unconditional love. I love you! iii TABLE OF CONTENTS ACKNOWLEDGEMENTS ....................................................................................
Load more

Recommended publications
  • Comprehensive Identification and Characterization of Somatic Copy Number Alterations in Triple‑Negative Breast Cancer
    INTERNATIONAL JOURNAL OF ONCOLOGY 56: 522-530, 2020 Comprehensive identification and characterization of somatic copy number alterations in triple‑negative breast cancer ZAIBING LI1,2*, XIAO ZHANG3*, CHENXIN HOU4, YUQING ZHOU4, JUNLI CHEN1, HAOYANG CAI5, YIFENG YE3, JINPING LIU3 and NING HUANG1 1Department of Pathophysiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041; 2Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan 646000; 3Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731; 4West China Medical School, Sichuan University, Chengdu, Sichuan 610041; 5Center of Growth, Metabolism and Aging, Key Laboratory of Bio‑Resources and Eco‑Environment, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, P.R. China Received January 30, 2019; Accepted August 30, 2019 DOI: 10.3892/ijo.2019.4950 Abstract. Triple-negative breast cancer (TNBC) accounts hierarchical clustering of tumors resulted in three main for ~15% of all breast cancer diagnoses each year. Patients subgroups that exhibited distinct CNA profiles, which with TNBC tend to have a higher risk for early relapse and may reveal the heterogeneity of molecular mechanisms in a worse prognosis. TNBC is characterized by extensive TNBC subgroups. These results will extend the molecular somatic copy number alterations (CNAs). However, the DNA understanding of TNBC and will facilitate the discovery of CNA profile of TNBC remains to be extensively investigated. therapeutic and diagnostic target candidates. The present study assessed the genomic profile of CNAs in 201 TNBC samples, aiming to identify recurrent CNAs that Introduction may drive the pathogenesis of TNBC.
    [Show full text]
  • Coordinate Regulation of Long Non-Coding Rnas and Protein-Coding Genes in Germ- Free Mice Joseph Dempsey, Angela Zhang and Julia Yue Cui*
    Dempsey et al. BMC Genomics (2018) 19:834 https://doi.org/10.1186/s12864-018-5235-3 RESEARCHARTICLE Open Access Coordinate regulation of long non-coding RNAs and protein-coding genes in germ- free mice Joseph Dempsey, Angela Zhang and Julia Yue Cui* Abstract Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of tissue-specific cellular functions and have been shown to regulate transcriptional and translational processes, acting as signals, decoys, guides, and scaffolds. It has been suggested that some lncRNAs act in cis to regulate the expression of neighboring protein-coding genes (PCGs) in a mechanism that fine-tunes gene expression. Gut microbiome is increasingly recognized as a regulator of development, inflammation, host metabolic processes, and xenobiotic metabolism. However, there is little known regarding whether the gut microbiome modulates lncRNA gene expression in various host metabolic organs. The goals of this study were to 1) characterize the tissue-specific expression of lncRNAs and 2) identify and annotate lncRNAs differentially regulated in the absence of gut microbiome. Results: Total RNA was isolated from various tissues (liver, duodenum, jejunum, ileum, colon, brown adipose tissue, white adipose tissue, and skeletal muscle) from adult male conventional and germ-free mice (n = 3 per group). RNA-Seq was conducted and reads were mapped to the mouse reference genome (mm10) using HISAT. Transcript abundance and differential expression was determined with Cufflinks using the reference databases NONCODE 2016 for lncRNAs and UCSC mm10 for PCGs. Although the constitutive expression of lncRNAs was ubiquitous within the enterohepatic (liver and intestine) and the peripheral metabolic tissues (fat and muscle) in conventional mice, differential expression of lncRNAs by lack of gut microbiota was highly tissue specific.
    [Show full text]
  • Serum Concentrations of Afamin Are Elevated in Patients with Polycystic Ovary Syndrome
    AKo¨ ninger et al. Afamin in patients with PCOS 1–7 3:120 Research Open Access Serum concentrations of afamin are elevated in patients with polycystic ovary syndrome Angela Ko¨ ninger, Philippos Edimiris, Laura Koch, Antje Enekwe, Claudia Lamina1, Sabine Kasimir-Bauer, Rainer Kimmig and Hans Dieplinger1,2 Correspondence Department of Gynecology and Obstetrics, University of Duisburg-Essen, D-45122 Essen, Germany should be addressed 1Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, to H Dieplinger Innsbruck Medical University, Scho¨ pfstrasse 41, A-6020 Innsbruck, Austria Email 2Vitateq Biotechnology GmbH, A-6020 Innsbruck, Austria [email protected] Abstract Oxidative stress seems to be present in patients with polycystic ovary syndrome (PCOS). Key Words The aim of this study was to evaluate the correlation between characteristics of PCOS and " vitamin E-binding protein serum concentrations of afamin, a novel binding protein for the antioxidant vitamin E. " afamin A total of 85 patients with PCOS and 76 control subjects were investigated in a pilot cross- " polycystic ovary syndrome sectional study design between 2009 and 2013 in the University Hospital of Essen, Germany. " oxidative stress Patients with PCOS were diagnosed according to the Rotterdam ESHRE/ASRM-sponsored " insulin resistance PCOS Consensus Workshop Group. Afamin and diagnostic parameters of PCOS were determined at early follicular phase. Afamin concentrations were significantly higher in Endocrine Connections patients with PCOS than in controls (odds ratio (OR) for a 10 mg/ml increase in afaminZ1.3, 95% CIZ1.08–1.58). This difference vanished in a model adjusting for age, BMI, free testosterone index (FTI), and sex hormone-binding globulin (SHBG) (ORZ1.05, 95% CIZ0.80–1.38).
    [Show full text]
  • Causal Varian Discovery in Familial Congenital Heart Disease - an Integrative -Omic Approach Wendy Demos Marquette University
    Marquette University e-Publications@Marquette Master's Theses (2009 -) Dissertations, Theses, and Professional Projects Causal Varian discovery in Familial Congenital Heart Disease - An Integrative -Omic Approach Wendy Demos Marquette University Recommended Citation Demos, Wendy, "Causal Varian discovery in Familial Congenital Heart Disease - An Integrative -Omic Approach" (2012). Master's Theses (2009 -). 140. https://epublications.marquette.edu/theses_open/140 CAUSAL VARIANT DISCOVERY IN FAMILIAL CONGENITAL HEART DISEASE – AN INTEGRATIVE –OMIC APPROACH by Wendy M. Demos A Thesis submitted to the Faculty of the Graduate School, Marquette University, in Partial Fulfillment of the Requirements for the Degree of Master of Science Milwaukee, Wisconsin May 2012 ABSTRACT CAUSAL VARIANT DISCOVERY IN FAMILIAL CONGENITAL HEART DISEASE – AN INTEGRATIVE –OMIC APPROACH Wendy M. Demos Marquette University, 2012 Background : Hypoplastic left heart syndrome (HLHS) is a congenital heart defect that leads to neonatal death or compromised quality of life for those affected and their families. This syndrome requires extensive medical intervention for the affected to survive. It is characterized by significant underdevelopment or non-existence of the components of the left heart and the aorta, including the left ventricular cavity and mass. There are many factors ranging from genetics to environmental relationships hypothesized to lead to the development of the syndrome, including recent studies suggesting a link between hearing impairment and congenital heart defects (CHD). Although broadly characterized those factors remain poorly understood. The goal of this project is to systematically utilize bioinformatics tools to determine the relationships of novel mutations found in exome sequencing to a familial congenital heart defect. Methods A systematic genomic and proteomic approach involving exome sequencing, pathway analysis, and protein modeling was implemented to examine exome sequencing data of a patient with HLHS.
    [Show full text]
  • Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights Into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle
    animals Article Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle Masoumeh Naserkheil 1 , Abolfazl Bahrami 1 , Deukhwan Lee 2,* and Hossein Mehrban 3 1 Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran; [email protected] (M.N.); [email protected] (A.B.) 2 Department of Animal Life and Environment Sciences, Hankyong National University, Jungang-ro 327, Anseong-si, Gyeonggi-do 17579, Korea 3 Department of Animal Science, Shahrekord University, Shahrekord 88186-34141, Iran; [email protected] * Correspondence: [email protected]; Tel.: +82-31-670-5091 Received: 25 August 2020; Accepted: 6 October 2020; Published: 9 October 2020 Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest.
    [Show full text]
  • Rabbit Anti-ZHX1 Antibody-SL19163R
    SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-ZHX1 antibody SL19163R Product Name: ZHX1 Chinese Name: 锌指及同源结构域蛋白1抗体 ZHX 1; ZHX1; ZHX1_HUMAN; Zinc finger and homeodomain protein 1; Zinc fingers Alias: and homeobox 1; Zinc fingers and homeoboxes 1; Zinc fingers and homeoboxes protein 1. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Cow,Horse,Sheep, ELISA=1:500-1000IHC-P=1:400-800IHC-F=1:400-800ICC=1:100-500IF=1:100- 500（Paraffin sections need antigen repair） Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 98kDa Cellular localization: The nucleus Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLHwww.sunlongbiotech.com conjugated synthetic peptide derived from human ZHX1:551-650/873 Lsotype: IgG Purification: affinity purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. PubMed: PubMed The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) Product Detail: and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains.
    [Show full text]
  • Growth and Molecular Profile of Lung Cancer Cells Expressing Ectopic LKB1: Down-Regulation of the Phosphatidylinositol 3؅-Phosphate Kinase/PTEN Pathway1
    [CANCER RESEARCH 63, 1382–1388, March 15, 2003] Growth and Molecular Profile of Lung Cancer Cells Expressing Ectopic LKB1: Down-Regulation of the Phosphatidylinositol 3؅-Phosphate Kinase/PTEN Pathway1 Ana I. Jimenez, Paloma Fernandez, Orlando Dominguez, Ana Dopazo, and Montserrat Sanchez-Cespedes2 Molecular Pathology Program [A. I. J., P. F., M. S-C.], Genomics Unit [O. D.], and Microarray Analysis Unit [A. D.], Spanish National Cancer Center, 28029 Madrid, Spain ABSTRACT the cell cycle in G1 (8, 9). However, the intrinsic mechanism by which LKB1 activity is regulated in cells and how it leads to the suppression Germ-line mutations in LKB1 gene cause the Peutz-Jeghers syndrome of cell growth is still unknown. It has been proposed that growth (PJS), a genetic disease with increased risk of malignancies. Recently, suppression by LKB1 is mediated through p21 in a p53-dependent LKB1-inactivating mutations have been identified in one-third of sporadic lung adenocarcinomas, indicating that LKB1 gene inactivation is critical in mechanism (7). In addition, it has been observed that LKB1 binds to tumors other than those of the PJS syndrome. However, the in vivo brahma-related gene 1 protein (BRG1) and this interaction is required substrates of LKB1 and its role in cancer development have not been for BRG1-induced growth arrest (10). Similar to what happens in the completely elucidated. Here we show that overexpression of wild-type PJS, Lkb1 heterozygous knockout mice show gastrointestinal hamar- LKB1 protein in A549 lung adenocarcinomas cells leads to cell-growth tomatous polyposis and frequent hepatocellular carcinomas (11, 12). suppression. To examine changes in gene expression profiles subsequent to Interestingly, the hamartomas, but not the malignant tumors, arising in exogenous wild-type LKB1 in A549 cells, we used cDNA microarrays.
    [Show full text]
  • Bioinformatic Analysis of Autism Positional Candidate Genes Using Biological Databases and Computational Gene Network Prediction
    Genes, Brain and Behavior (2003) 2: 303–320 Copyright # Blackwell Munksgaard 2003 Bioinformatic analysis of autism positional candidate genes using biological databases and computational gene network prediction A. L. Yonan†,‡, A. A. Palmer†, K. C. Smith†, inform studies of autism, and to illustrate and explore I. Feldman†,††, H. K. Lee†, J. M. Yonan§, the increasing potential of bioinformatic approaches as † †,†† *,†,‡, S. G. Fischer , P. Pavlidis and T. C. Gilliam { a compliment to linkage analysis. Keywords: 17q, AGRE sample, autism, association studies, †Columbia Genome Center, Columbia University, New York, bioinformatics, candidate genes ‡ Department of Genetics and Development, Columbia University, Received 30 June 2003, revised 20 August 2003, accepted New York, for publication 21 August 2003 ¶Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, §Division of Molecular Genetics, Departments of Pediatrics and Medicine, Columbia University, New York, Autism is a pervasive neurodevelopmental disorder that ††Department of Biomedical Informatics, Columbia University, severely impairs development of normal social and emotional New York, USA interactions and related forms of communication. Disease *Corresponding author: T. C. Gilliam, Columbia Genome Center, symptoms characteristically include unusually restricted and 1150 St. Nicholas Avenue, Room 508, New York, NY 10032, USA. E-mail: [email protected] stereotyped patterns of behaviors and interests. Autism describes the most severe manifestation
    [Show full text]
  • Entrez Exercises
    1 NCBI Exercises 1/12/2007 Entrez Exercises Global Query: Controlled Vocabularies and Limits Type the word “cancer” in the search box on the NCBI homepage and run the search. This query returns results in all of the Entrez databases. However the query is interpreted differently in different databases. PubMed Retrieve the result for the PubMed database. Click the “Details” tab to see how the query was interpreted in this database. Notice that the term cancer was translated to the Medical Subject Heading (MeSH) term “neoplasms” ("neoplasms"[MeSH Terms]). 2 NCBI Exercises 1/12/2007 MeSH is a controlled vocabulary that is used to index all articles in PubMed. In the details box, edit the query to remove the portion that searched for cancer as a text word and run the search. Notice that the number of articles retrieved has changed. These will be a more relevant set of results. You can force the PubMed engine to only search the MeSH vocabulary or specify any other indexed field through the “Limits” tab. Use the Web browser’s back button to return to the Global query page and retrieve the PubMed results again. Now click on the “Limits” tab. Select “MeSH terms” from the first drop-down menu, the one headed by “All Fields”. Now run the search with the limit in place and check the “Details” tab to verify that only the MeSH term translation was used. Nucleotide Use the Web browser’s back button to return to the Global query page. Retrieve the results for the nucleotide database. 3 NCBI Exercises 1/12/2007 The Nucleotide database in the Global query is now three separate databases.
    [Show full text]
  • Proteomic Analysis Reveals a Mitochondrial Remodeling of Βtc3 Cells in Response to Nanotopography
    fcell-08-00508 July 29, 2020 Time: 12:23 # 1 ORIGINAL RESEARCH published: 29 July 2020 doi: 10.3389/fcell.2020.00508 Proteomic Analysis Reveals a Mitochondrial Remodeling of bTC3 Cells in Response to Nanotopography Elisa Maffioli1,2†, Alessandra Galli3†, Simona Nonnis1,2, Algerta Marku3, Armando Negri1, Claudio Piazzoni2,4, Paolo Milani2,4, Cristina Lenardi2,4, Carla Perego3* and Gabriella Tedeschi1,2* 1 Department of Veterinary Medicine, University of Milano, Milan, Italy, 2 Centre for Nanostructured Materials and Interfaces, University of Milano, Milan, Italy, 3 Department of Pharmacological and Biomolecular Sciences, University of Milano, Milan, Italy, 4 Department of Physics, University of Milano, Milan, Italy Edited by: Recently, using cluster-assembled zirconia substrates with tailored roughness produced Luisa Pieroni, Santa Lucia Foundation (IRCCS), Italy by supersonic cluster beam deposition, we demonstrated that b cells can sense Reviewed by: nanoscale features of the substrate and can translate these stimuli into a Massimiliano Galluzzi, mechanotransductive pathway capable of preserveing b-cell differentiation and function Chinese Academy of Sciences (CAS), in vitro in long-term cultures of human islets. Using the same proteomic approach, China Geeta Upadhyay, we now focused on the mitochondrial fraction of bTC3 cells grown on the same Uniformed Services University of the zirconia substrates and characterized the morphological and proteomic modifications Health Sciences, United States Gian Maria Fimia, induced by the nanostructure. The results suggest that, in bTC3 cells, mitochondria Sapienza University of Rome, Italy are perturbed by the nanotopography and activate a program involving metabolism *Correspondence: modification and modulation of their interplay with other organelles. Data were confirmed Carla Perego in INS1E, a different b-cell model.
    [Show full text]
  • Collapse of the Hepatic Gene Regulatory Network in the Absence of Foxa Factors
    bioRxiv preprint doi: https://doi.org/10.1101/2020.03.31.016006; this version posted April 1, 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. Collapse of the hepatic gene regulatory network in the absence of FoxA factors Yitzhak Reizel1, Ashleigh Morgan1, Long Gao1, Yemin Lan2, Elisabetta Manduchi3, Eric L. Waite1, Amber W. Wang1, Andrew Wells4, and Klaus H. Kaestner1* 1Department of Genetics, University of Pennsylvania, Philadelphia, PA 2Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 3Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania, Philadelphia, PA 4Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA *Correspondence to: Klaus H Kaestner at [email protected] Phone: 215-898-8759 Fax: 215-573-5892 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.03.31.016006; this version posted April 1, 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 FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid hepatocyte dedifferentiation manifested by a massive reduction in the expression of key liver genes. Interestingly, expression of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days.
    [Show full text]
  • Quantitative SUMO Proteomics Reveals the Modulation of Several
    www.nature.com/scientificreports OPEN Quantitative SUMO proteomics reveals the modulation of several PML nuclear body associated Received: 10 October 2017 Accepted: 28 March 2018 proteins and an anti-senescence Published: xx xx xxxx function of UBC9 Francis P. McManus1, Véronique Bourdeau2, Mariana Acevedo2, Stéphane Lopes-Paciencia2, Lian Mignacca2, Frédéric Lamoliatte1,3, John W. Rojas Pino2, Gerardo Ferbeyre2 & Pierre Thibault1,3 Several regulators of SUMOylation have been previously linked to senescence but most targets of this modifcation in senescent cells remain unidentifed. Using a two-step purifcation of a modifed SUMO3, we profled the SUMO proteome of senescent cells in a site-specifc manner. We identifed 25 SUMO sites on 23 proteins that were signifcantly regulated during senescence. Of note, most of these proteins were PML nuclear body (PML-NB) associated, which correlates with the increased number and size of PML-NBs observed in senescent cells. Interestingly, the sole SUMO E2 enzyme, UBC9, was more SUMOylated during senescence on its Lys-49. Functional studies of a UBC9 mutant at Lys-49 showed a decreased association to PML-NBs and the loss of UBC9’s ability to delay senescence. We thus propose both pro- and anti-senescence functions of protein SUMOylation. Many cellular mechanisms of defense have evolved to reduce the onset of tumors and potential cancer develop- ment. One such mechanism is cellular senescence where cells undergo cell cycle arrest in response to various stressors1,2. Multiple triggers for the onset of senescence have been documented. While replicative senescence is primarily caused in response to telomere shortening3,4, senescence can also be triggered early by a number of exogenous factors including DNA damage, elevated levels of reactive oxygen species (ROS), high cytokine signa- ling, and constitutively-active oncogenes (such as H-RAS-G12V)5,6.
    [Show full text]