Gene Set Analysis and Reduction for a Continuous Phenotype Identifying
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Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and C-JUN to Bypass PUMILIO Post-Transcriptional Regulation
Author Manuscript Published OnlineFirst on October 10, 2016; DOI: 10.1158/0008-5472.CAN-16-0844 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Title: Alternative polyadenylation in triple-negative breast tumors allows NRAS and c-JUN to bypass PUMILIO post-transcriptional regulation Running Title: Alternative polyadenylation in triple-negative breast cancer Authors: Wayne O. Miles 1, 2, 7, Antonio Lembo 3, 4, Angela Volorio 5, Elena Brachtel 5, Bin Tian 6, Dennis Sgroi 5, Paolo Provero 3, 4 and Nicholas J. Dyson 1, 7 1 Department of Molecular Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, MA, 02129, USA. 2 Department of Molecular Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210 3 Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy. 4 Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy. 5 Pathology Department, Massachusetts General Hospital Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, MA, 02129, USA. 6 Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, USA 7 Corresponding authors: [email protected] (N.D.) and [email protected] (W.O.M.) Conflict of interest The authors have no conflict of interest. Financial Support 1 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 2016 American Association for Cancer Research. Author Manuscript Published OnlineFirst on October 10, 2016; DOI: 10.1158/0008-5472.CAN-16-0844 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. -
Analysis of Trans Esnps Infers Regulatory Network Architecture
Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2014 Anat Kreimer All rights reserved ABSTRACT Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer eSNPs are genetic variants associated with transcript expression levels. The characteristics of such variants highlight their importance and present a unique opportunity for studying gene regulation. eSNPs affect most genes and their cell type specificity can shed light on different processes that are activated in each cell. They can identify functional variants by connecting SNPs that are implicated in disease to a molecular mechanism. Examining eSNPs that are associated with distal genes can provide insights regarding the inference of regulatory networks but also presents challenges due to the high statistical burden of multiple testing. Such association studies allow: simultaneous investigation of many gene expression phenotypes without assuming any prior knowledge and identification of unknown regulators of gene expression while uncovering directionality. This thesis will focus on such distal eSNPs to map regulatory interactions between different loci and expose the architecture of the regulatory network defined by such interactions. We develop novel computational approaches and apply them to genetics-genomics data in human. We go beyond pairwise interactions to define network motifs, including regulatory modules and bi-fan structures, showing them to be prevalent in real data and exposing distinct attributes of such arrangements. We project eSNP associations onto a protein-protein interaction network to expose topological properties of eSNPs and their targets and highlight different modes of distal regulation. -
ACTR2 Antibody / Arp2 (RQ5865)
ACTR2 Antibody / Arp2 (RQ5865) Catalog No. Formulation Size RQ5865 0.5mg/ml if reconstituted with 0.2ml sterile DI water 100 ug Bulk quote request Availability 1-3 business days Species Reactivity Human, Mouse, Rat, Monkey Format Antigen affinity purified Clonality Polyclonal (rabbit origin) Isotype Rabbit IgG Purity Affinity purified Buffer Lyophilized from 1X PBS with 2% Trehalose and 0.025% sodium azide UniProt P61160 Applications Western blot : 0.5-1ug/ml Immunohistochemistry : 1-2ug/ml Immunofluorescence : 2-4ug/ml Flow cytometry : 1-3ug/million cells Direct ELISA : 0.1-0.5ug/ml Limitations This ACTR2 antibody is available for research use only. IHC staining of FFPE human breast cancer with ACTR2 antibody. HIER: boil tissue sections in pH8 EDTA for 20 min and allow to cool before testing. Immunofluorescent staining of FFPE human A549 cells with ACTR2 antibody (green) and DAPI nuclear stain (blue). HIER: steam section in pH6 citrate buffer for 20 min. Western blot testing of 1) rat kidney, 2) rat spleen, 3) mouse HEPA1-6, 4) mouse SP2/0, 5) monkey COS-7 and human 6) U-87 MG, 7) Jurkat, 8) PC-3 and 9) U-2 OS lysate with ACTR2 antibody. Predicted molecular weight ~45 kDa. Flow cytometry testing of human A431 cells with ACTR2 antibody at 1ug/million cells (blocked with goat sera); Red=cells alone, Green=isotype control, Blue= ACTR2 antibody. Flow cytometry testing of mouse ANA-1 cells with ACTR2 antibody at 1ug/million cells (blocked with goat sera); Red=cells alone, Green=isotype control, Blue= ACTR2 antibody. Description The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. -
Anti-MRPS18B Antibody
D225370 Anti-MRPS18B antibody Cat. No. D225370 Package 25 μl/100 μl/200 μl Storage -20°C, pH7.4 PBS, 0.05% NaN3, 40% Glycerol Product overview Description A n ti-MRPS18B rabbit polyclonal antibody Applications ELISA, WB, IHC Immunogen Fusion protein of human MRPS18B Reactivity Human Content 1 mg/ml Host species Rabbit Ig class Immunogen-specific rabbit IgG Purification Antigen affinity purification Target information Symbol MRPS18B Full name mitochondrial ribosomal protein S18B Synonyms PTD017; S18amt; C6orf14; HSPC183; MRPS18-2; HumanS18a; MRP-S18-2 Swissprot Q9Y676 Target Background Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S18P family. The encoded protein is one of three that has significant sequence similarity to bacterial S18 proteins. The primary sequences of the three human mitochondrial S18 proteins are no more closely reSlated to angoneach other than they are to the prok aryBiotic S18 proteins. tPseuedogenches corresponding to this gene are found on chromosomes 1q and 2q. Applications Immunohistochemistry Predicted cell location: Cytoplasm Positive control: Human tonsil Recommended dilution: 25-100 The image on the left is immunohistochemistry of paraffin-embedded Human tonsil tissue using D225370(MRPS18B Antibody) at dilution 1/55, on the right is treated with fusion protein. -
Regulation of Pluripotency by RNA Binding Proteins
Cell Stem Cell Review Regulation of Pluripotency by RNA Binding Proteins Julia Ye1,2 and Robert Blelloch1,2,* 1The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA 2Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.stem.2014.08.010 Establishment, maintenance, and exit from pluripotency require precise coordination of a cell’s molecular machinery. Substantial headway has been made in deciphering many aspects of this elaborate system, particularly with respect to epigenetics, transcription, and noncoding RNAs. Less attention has been paid to posttranscriptional regulatory processes such as alternative splicing, RNA processing and modification, nuclear export, regulation of transcript stability, and translation. Here, we introduce the RNA binding proteins that enable the posttranscriptional regulation of gene expression, summarizing current and ongoing research on their roles at different regulatory points and discussing how they help script the fate of pluripotent stem cells. Introduction RBPs are responsible for every event in the life of an RNA Embryonic stem cells (ESCs), which are derived from the inner molecule, including its capping, splicing, cleavage, nontem- cell mass of the mammalian blastocyst, are remarkable because plated nucleotide addition, nucleotide editing, nuclear export, they can propagate in vitro indefinitely while retaining both the cellular localization, stability, and translation (Keene, 2007). molecular identity and the pluripotent properties of the peri-im- Overall, little is known about RBPs: most are classified based plantation epiblast. -
Structural Basis for the Regulatory Interactions of Proapoptotic Par-4
Cell Death and Differentiation (2017) 24, 1540–1547 Official journal of the Cell Death Differentiation Association OPEN www.nature.com/cdd Structural basis for the regulatory interactions of proapoptotic Par-4 Udaya K Tiruttani Subhramanyam1,2, Jan Kubicek2,3, Ulf B Eidhoff2 and Joerg Labahn*,1,2 Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization. The heteromeric-interaction models specifically showed that charge interaction is an important factor in the stability of heteromers of the C-terminal leucine zipper subdomain of Par-4 (Par-4LZ). These heteromer models also displayed NES masking capacity and therefore the ability to influence intracellular localization. Cell Death and Differentiation (2017) 24, 1540–1547; doi:10.1038/cdd.2017.76; published online 16 June 2017 Par-4 is a 332 amino-acid proapoptotic protein with tumor mainly shown to mediates the interaction with partner proteins suppressor activity. Par-4 had been predicted to be largely such as PKCζ,15 WT1,16 Akt1,13 apoptosis antagonizing disordered.1 Its downregulation or non-functional state -
CRAVAT 4: Cancer-Related Analysis of Variants Toolkit David L
Cancer Focus on Computer Resources Research CRAVAT 4: Cancer-Related Analysis of Variants Toolkit David L. Masica1,2, Christopher Douville1,2, Collin Tokheim1,2, Rohit Bhattacharya2,3, RyangGuk Kim4, Kyle Moad4, Michael C. Ryan4, and Rachel Karchin1,2,5 Abstract Cancer sequencing studies are increasingly comprehensive and level interpretation, including joint prioritization of all nonsilent well powered, returning long lists of somatic mutations that can be mutation consequence types, and structural and mechanistic visu- difficult to sort and interpret. Diligent analysis and quality control alization. Results from CRAVAT submissions are explored in an can require multiple computational tools of distinct utility and interactive, user-friendly web environment with dynamic filtering producing disparate output, creating additional challenges for the and sorting designed to highlight the most informative mutations, investigator. The Cancer-Related Analysis of Variants Toolkit (CRA- even in the context of very large studies. CRAVAT can be run on a VAT) is an evolving suite of informatics tools for mutation inter- public web portal, in the cloud, or downloaded for local use, and is pretation that includes mutation mapping and quality control, easily integrated with other methods for cancer omics analysis. impact prediction and extensive annotation, gene- and mutation- Cancer Res; 77(21); e35–38. Ó2017 AACR. Background quickly returning mutation interpretations in an interactive and user-friendly web environment for sorting, visualizing, and An investigator's work is far from over when results are returned inferring mechanism. CRAVAT (see Supplementary Video) is from the sequencing center. Depending on the service, genetic suitable for large studies (e.g., full-exome and large cohorts) mutation calls can require additional mapping to include all and small studies (e.g., gene panel or single patient), performs relevant RNA transcripts or correct protein sequences. -
S41467-020-18249-3.Pdf
ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible. -
Noelia Díaz Blanco
Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr. -
Variation in Protein Coding Genes Identifies Information
bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number. -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Downloaded the “Top Edge” Version
bioRxiv preprint doi: https://doi.org/10.1101/855338; this version posted December 6, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Drosophila models of pathogenic copy-number variant genes show global and 2 non-neuronal defects during development 3 Short title: Non-neuronal defects of fly homologs of CNV genes 4 Tanzeen Yusuff1,4, Matthew Jensen1,4, Sneha Yennawar1,4, Lucilla Pizzo1, Siddharth 5 Karthikeyan1, Dagny J. Gould1, Avik Sarker1, Yurika Matsui1,2, Janani Iyer1, Zhi-Chun Lai1,2, 6 and Santhosh Girirajan1,3* 7 8 1. Department of Biochemistry and Molecular Biology, Pennsylvania State University, 9 University Park, PA 16802 10 2. Department of Biology, Pennsylvania State University, University Park, PA 16802 11 3. Department of Anthropology, Pennsylvania State University, University Park, PA 16802 12 4 contributed equally to work 13 14 *Correspondence: 15 Santhosh Girirajan, MBBS, PhD 16 205A Life Sciences Building 17 Pennsylvania State University 18 University Park, PA 16802 19 E-mail: [email protected] 20 Phone: 814-865-0674 21 1 bioRxiv preprint doi: https://doi.org/10.1101/855338; this version posted December 6, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 22 ABSTRACT 23 While rare pathogenic copy-number variants (CNVs) are associated with both neuronal and non- 24 neuronal phenotypes, functional studies evaluating these regions have focused on the molecular 25 basis of neuronal defects.