DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2012/0322864 A1 Rossi Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2012/0322864 A1 Rossi Et Al US 2012O322864A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0322864 A1 Rossi et al. (43) Pub. Date: Dec. 20, 2012 (54) SUSTAINED POLYPEPTIDE EXPRESSION (60) Provisional application No. 61/325,003, filed on Apr. FROM SYNTHETIC, MODIFIED RNAS AND 16, 2010, provisional application No. 61/387,220, USES THEREOF filed on Sep. 28, 2010. Publication Classification (75) Inventors: Derrick Rossi, Roslindale, MA (US); (51) Int. Cl. Luigi Warren, Cambridge, MA (US) CI2N5/07 (2010.01) A6IR 48/00 (2006.01) (73) Assignee: IMMUNE DISEASE INSTITUTE, C7H 2L/02 (2006.01) INC., Boston, MA (US) (52) U.S. Cl. ...................... 514/44 R; 536/23.5; 435/377 (57) ABSTRACT (21) Appl. No.: 13/590,880 Described herein are synthetic, modified RNAs for changing the phenotype of a cell. Such as expressing a polypeptide or altering the developmental potential. Accordingly, provided (22) Filed: Aug. 21, 2012 herein are compositions, methods, and kits comprising Syn thetic, modified RNAs for changing the phenotype of a cellor Related U.S. Application Data cells. These methods, compositions, and kits comprising Syn thetic, modified RNAs can be used either to express a desired (63) Continuation of application No. 13/088,009, filed on protein in a cell or tissue, or to change the differentiated Apr. 15, 2011. phenotype of a cell to that of another, desired cell type. Patent Application Publication Dec. 20, 2012 Sheet 1 of 45 US 2012/0322864 A1 s se xxx S s s nnnn s e sit. occa S. s Ra w s e s S. iiii is is iiiiSE SEE SS Patent Application Publication Dec. 20, 2012 Sheet 2 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 3 of 45 US 2012/0322864 A1 t S is is is is Patent Application Publication Dec. 20, 2012 Sheet 4 of 45 US 2012/0322864 A1 . S -- Patent Application Publication Dec. 20, 2012 Sheet 5 of 45 US 2012/0322864 A1 S. s s Unive -- Patent Application Publication Dec. 20, 2012 Sheet 6 of 45 US 2012/0322864 A1 S is Patent Application Publication Dec. 20, 2012 Sheet 7 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 8 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 9 of 45 US 2012/0322864 A1 waxes --- s as --ur VEHICLEvict- sa- i--1 -- awarr -21 --- in--si s 40 a-21 Patent Application Publication Dec. 20, 2012 Sheet 10 of 45 US 2012/0322864 A1 y/GEN/A GE/ Patent Application Publication Dec. 20, 2012 Sheet 11 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 12 of 45 US 2012/0322864 A1 ESSES Patent Application Publication Dec. 20, 2012 Sheet 13 of 45 US 2012/0322864 A1 & I FE : E 3 3 e s . R : 2e 18- , 75 / : : 8.5 - | r i s a 25 ------e.cc cc------8 ESSES Patent Application Publication Dec. 20, 2012 Sheet 14 of 45 US 2012/0322864 A1 s af s ar r sees i s S & & -: Elie :FSF C S: : C. SS cricEFSF Š 3. is S. S. is FEF, Patent Application Publication Dec. 20, 2012 Sheet 15 of 45 US 2012/0322864 A1 e R s co S itr s -S SE i- An s S X ŠE : Š t t c F3 Š"A. 88: ESF: i F: c :: : E. F8 88: ce i. Liz st Esfia. Š. it 3. ii Patent Application Publication Dec. 20, 2012 Sheet 16 of 45 US 2012/0322864 A1 Sii . iii. iii. i i i Patent Application Publication Dec. 20, 2012 Sheet 17 of 45 US 2012/0322864 A1 V,±01. S is Patent Application Publication Dec. 20, 2012 Sheet 18 of 45 US 2012/0322864 A1 f is is a SESSFEEE Patent Application Publication Dec. 20, 2012 Sheet 19 of 45 US 2012/0322864 A1 Šis stŠ Patent Application Publication Dec. 20, 2012 Sheet 20 of 45 US 2012/0322864 A1 SE --S ECS i sstss s s s s Patent Application Publication Dec. 20, 2012 Sheet 21 of 45 US 2012/0322864 A1 SE-i ECES E. sssi s (cont Patent Application Publication Dec. 20, 2012 Sheet 22 of 45 US 2012/0322864 A1 8 Patent Application Publication Dec. 20, 2012 Sheet 23 of 45 US 2012/0322864 A1 & S S & Š & ::::: s Patent Application Publication Dec. 20, 2012 Sheet 24 of 45 US 2012/0322864 A1 ES SS i. Patent Application Publication Dec. 20, 2012 Sheet 25 of 45 US 2012/0322864 A1 ES -- SS i. e Patent Application Publication Dec. 20, 2012 Sheet 26 of 45 US 2012/0322864 A1 ES SE s SS S. S S. S S. S SS S.S S S. S SS S. Patent Application Publication Dec. 20, 2012 Sheet 27 of 45 US 2012/0322864 A1 ES SS Patent Application Publication Dec. 20, 2012 Sheet 28 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 29 of 45 US 2012/0322864 A1 i 2 UNTRANSFEED as RNA Patent Application Publication Dec. 20, 2012 Sheet 31 of 45 US 2012/0322864 A1 SS S. C.S. 8 REY FRPS 8 Patent Application Publication Dec. 20, 2012 Sheet 32 of 45 US 2012/0322864 A1 : SS Patent Application Publication Dec. 20, 2012 Sheet 33 of 45 US 2012/0322864 A1 i. s ES Patent Application Publication Dec. 20, 2012 Sheet 34 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 35 of 45 US 2012/0322864 A1 ST ST SS ES TS 'S EST ST ST SS STSs TST cE--------. ST S. Seii. St. i Seii. "Set" Seii: S8. for-o-o-o-o-Too Patent Application Publication Dec. 20, 2012 Sheet 36 of 45 US 2012/0322864 A1 s s s s s s s s t s &S se s Patent Application Publication Dec. 20, 2012 Sheet 37 of 45 US 2012/0322864 A1 / if: Patent Application Publication Dec. 20, 2012 Sheet 38 of 45 US 2012/0322864 A1 Sir S: Patent Application Publication Dec. 20, 2012 Sheet 39 of 45 US 2012/0322864 A1 i SS s as Patent Application Publication Dec. 20, 2012 Sheet 40 of 45 US 2012/0322864 A1 8 s E ste see E3road is 489 ... sis 8a st w a s ocw. Patent Application Publication Dec. 20, 2012 Sheet 41 of 45 US 2012/0322864 A1 Patent Application Publication Dec. 20, 2012 Sheet 42 of 45 US 2012/0322864 A1 s See sts sis do is ses e e S. at ... - Ese E.ses s: s s s E se e.g. E es s s se s is - s s se se sixx 8ws w Yw x wwwe $8 *or S. s SS - rrrr s E. es is . do s Patent Application Publication Dec. 20, 2012 Sheet 43 of 45 US 2012/0322864 A1 . 3 4. E. s 32 24 s S is is a e S S S Patent Application Publication Dec. 20, 2012 Sheet 44 of 45 US 2012/0322864 A1 ############### $######### #####$#ffff; ######3 ~,,• ####### --- $###$ ~,,•••• ################################# ############# ############ --??• '$######### ############### ########################~### Patent Application Publication Dec. 20, 2012 Sheet 45 of 45 US 2012/0322864 A1 e yer i US 2012/0322864 A1 Dec. 20, 2012 SUSTAINED POLYPEPTIDE EXPRESSION N., et al., Proc.Jpn Acad Ser B Phy's Biol Sci, 2009.85(8): p. FROM SYNTHETIC, MODIFIED RNAS AND 348-62). Human pluripotent cells have also been derived USES THEREOF using two DNA-free methods: serial protein transduction with recombinant proteins incorporating cell-penetrating CROSS-REFERENCE TO RELATED peptide moieties (Kim, D., et al., Cell Stem Cell, 2009. 4(6): APPLICATIONS p. 472-476: Zhou, H., et al., Cell Stem Cell, 2009. 4(5): p. 0001. This application is a continuation application under 381-4), and infectious transgene delivery using the Sendai 35 U.S.C. S 120 of a co-pending U.S. application Ser. No. virus, which has a completely RNA-based reproductive cycle 13/088,009 filed on Apr. 15, 2011, which claims benefit under (Fusaki, N., et al., Proc.Jpn. Acad Ser B Phy's BiolSci, 2009. 35 U.S.C. S 119(e) of U.S. Provisional Patent Application Ser. 85(8): p. 348-62). No. 61/325,003 filed on Apr. 16, 2010 and U.S. Provisional Patent Application Ser. No. 61/387,220 filed on Sep. 28, SUMMARY 2010, the contents of which are incorporated herein by refer 0007 Provided herein are compositions, methods, and kits ence in their entirety. for changing the phenotype of a cell or cells. These methods, compositions, and kits can be used either to express a desired SEQUENCE LISTING protein in a cell or tissue, or to change the differentiated 0002 The instant application contains a Sequence Listing phenotype of a cell to that of another, desired cell type. which has been submitted in ASCII format via EFS-Web and Significantly, the methods, compositions, and kits described is hereby incorporated by reference in its entirety. Said ASCII herein do not utilize exogenous DNA or viral vector-based methods for the expression of protein(s), and thus, do not copy, created on Apr. 8, 2011, is named 67443US1.txt and is cause permanent modification of the genome or have the 7,196,077 bytes in size. potential for unintended mutagenic effects. FIELD OF THE INVENTION 0008. The compositions, methods, and kits described herein are based upon the direct introduction of synthetic 0003. The field of the invention relates to synthetic, modi RNAs into a cell, which, when translated, provide a desired fied RNAs and uses thereof.
Load more

Recommended publications
  • Table 2. Significant
    Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S.
    [Show full text]
  • Erk Direction of CD4 T Cell Subsets Chiung-Fang Chang, Warren N
    Polar Opposites: Erk Direction of CD4 T Cell Subsets Chiung-Fang Chang, Warren N. D'Souza, Irene L. Ch'en, Gilles Pages, Jacques Pouyssegur and Stephen M. Hedrick This information is current as of September 25, 2021. J Immunol 2012; 189:721-731; Prepublished online 6 June 2012; doi: 10.4049/jimmunol.1103015 http://www.jimmunol.org/content/189/2/721 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2012/06/06/jimmunol.110301 Material 5.DC1 References This article cites 67 articles, 28 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/189/2/721.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 25, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Polar Opposites: Erk Direction of CD4 T Cell Subsets Chiung-Fang Chang,* Warren N. D’Souza,† Irene L.
    [Show full text]
  • Atbf1 Is Required for the Pit1 Gene Early Activation
    Atbf1 is required for the Pit1 gene early activation Yingchuan Qi*, Jeffrey A. Ranish†, Xiaoyan Zhu*, Anna Krones*, Jie Zhang*, Ruedi Aebersold†‡, David W. Rose§, Michael G. Rosenfeld*¶, and Catherine Carrie` re¶ʈ *Howard Hughes Medical Institute and Department of Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093; †Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; ‡Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Ho¨nggerberg and Faculty of Sciences, University of Zu¨rich, CH-8093 Zu¨rich, Switzerland; §Department of Medicine, Division of Endocrinology and Metabolism, School of Medicine, University of California at San Diego, La Jolla, CA 92093; and ʈDepartment of Medicine, Dartmouth Medical School, Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, NH 03756 Contributed by Michael G. Rosenfeld, December 24, 2007 (sent for review November 28, 2007) Enhancers have been functionally described for >35 years, but the Pit1-defective Snell (dw/dw) mutant mice, demonstrating that the molecular principles underlying the integration of regulatory in- elements required for Pit1 early activation were present in the same puts to alternate gene enhancers used during mammalian orga- genomic region (10). Further mapping showed that the regions nogenesis remain incompletely understood. Using a combination required for the Pit1 early activation were located between Ϫ10 kb of in vivo enhancer mapping and proteomics approaches, we have and Ϫ3.5 kb (10). Thus, Pit1 expression appears to be under the established that two distant and distinct early enhancers, each control of multiple enhancers, at least one for its activation and one requiring different transcription complexes, are required for full for its maintained expression.
    [Show full text]
  • Gene Expression Profile of Amyloid Beta Protein-Injected Mouse Model for Alzheimer Disease
    Acta Pharmacologica Sinica 2005 Jun; 26 (6): 666–672 Full-length article Gene expression profile of amyloid beta protein-injected mouse model for Alzheimer disease Ling-na KONG, Ping-ping ZUO1, Liang MU, Yan-yong LIU, Nan YANG Department of Pharmacology, School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China Key words Abstract Alzheimer disease; dementia; amyloid beta- Aim: To investigate the gene expression profile changes in the cerebral cortex of protein; cDNA microarray mice injected icv with amyloid beta-protein (Aβ) fragment 25-35 using cDNA microarray. Methods: Balb/c mice were randomly divided into a control group and 1 Correspondence to Prof Ping-ping ZUO. Aβ-treated group. The Morris water maze test was performed to detect the effect Phn/Fax 86-10-6529-6404. of Aβ-injection on the learning and memory of mice. Atlas Mouse 1.2 Expression E-mail [email protected] Arrays containing 1176 genes were used to investigate the gene expression pat- Received 2004-11-25 tern of each group. Results: The gene expression profiles showed that 19 genes Accepted 2005-03-14 including TBX1, NF-κB, AP-1/c-Jun, cadherin, integrin, erb-B2, and FGFR1 were doi: 10.1111/j.1745-7254.2005.00129.x up-regulated after 2 weeks of icv administration of Aβ; while 12 genes were down- regulated, including NGF, glucose phosphate isomerase 1, AT motif binding fac- tor 1, Na+/K+-ATPase, and Akt. Conclusions: The results provide important leads for pursuing a more complete understanding of the molecular events of Aβ- injection into mice with Alzheimer disease.
    [Show full text]
  • Regulation of Skeletal Muscle Differentiation by ATBF1, a Multiple Homeodomain-Zinc Finger Transcription Factor
    University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies Legacy Theses 2000 Regulation of skeletal muscle differentiation by ATBF1, a multiple homeodomain-zinc finger transcription factor Berry, Fred Brandon Berry, F. B. (2000). Regulation of skeletal muscle differentiation by ATBF1, a multiple homeodomain-zinc finger transcription factor (Unpublished doctoral thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/23689 http://hdl.handle.net/1880/39899 doctoral thesis University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. Downloaded from PRISM: https://prism.ucalgary.ca NOTE TO USERS Page(s) not included in the original manuscript and are unavailable from the author or university. The manuscript was microfilmed as received. This reproduction is the best copy available. THE UNIVERSITY OF CALGARY Regulation of Skeletal MuscIe Differentiation by ATBF1, a Multiple Homeodomain-zinc Finger Transcription Factor Fred Brandon Berry A DISSERTATION SUBMITTED TO THlE FACC?TYOF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY CALGARY, ALBERTA APRIL, 2000 O Fred Brandon Berry 2000 National Library Bibliotheque nationale I+IofCanada
    [Show full text]
  • Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay Between Cell- Autonomous and Circuit-Level Mechanisms
    Downloaded from http://cshperspectives.cshlp.org/ on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell- Autonomous and Circuit-Level Mechanisms Erik D. Herzog,1 Tracey Hermanstyne,1 Nicola J. Smyllie,2 and Michael H. Hastings2 1Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130-4899 2Division of Neurobiology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom Correspondence: [email protected]; [email protected] The suprachiasmatic nucleus (SCN) is the principal circadian clock of the brain, directing daily cycles of behavior and physiology. SCN neurons contain a cell-autonomous transcrip- tion-based clockwork but, in turn, circuit-level interactions synchronize the 20,000 or so SCN neurons into a robust and coherent daily timer. Synchronization requires neuropeptide signaling, regulated by a reciprocal interdependence between the molecular clockwork and rhythmic electrical activity, which in turn depends on a daytime Naþ drive and nighttime Kþ drag. Recent studies exploiting intersectional genetics have started to identify the pacemak- ing roles of particular neuronal groups in the SCN. They support the idea that timekeeping involves nonlinear and hierarchical computations that create and incorporate timing infor- mation through the interactions between key groups of neurons within the SCN circuit. The field is now poised to elucidate these computations, their underlying cellular mechanisms, and how the SCN clock interacts with subordinate circadian clocks across the brain to determine the timing and efficiency of the sleep–wake cycle, and how perturbations of this coherence contribute to neurological and psychiatric illness.
    [Show full text]
  • Spatial and Temporal Patterns of Gene Expression During Neurogenesis in the Sea Urchin Lytechinus Variegatus Leslie A
    Slota et al. EvoDevo (2019) 10:2 https://doi.org/10.1186/s13227-019-0115-8 EvoDevo RESEARCH Open Access Spatial and temporal patterns of gene expression during neurogenesis in the sea urchin Lytechinus variegatus Leslie A. Slota , Esther M. Miranda and David R. McClay* Abstract Background: The sea urchin is a basal deuterostome that is more closely related to vertebrates than many organisms traditionally used to study neurogenesis. This phylogenetic position means that the sea urchin can provide insights into the evolution of the nervous system by helping resolve which developmental processes are deuterostome inno- vations, which are innovations in other clades, and which are ancestral. However, the nervous system of echinoderms is one of the least understood of all major metazoan phyla. To gain insights into echinoderm neurogenesis, spatial and temporal gene expression data are essential. Then, functional data will enable the building of a detailed gene regula- tory network for neurogenesis in the sea urchin that can be compared across metazoans to resolve questions about how nervous systems evolved. Results: Here, we analyze spatiotemporal gene expression during sea urchin neurogenesis for genes that have been shown to be neurogenic in one or more species. We report the expression of 21 genes expressed in areas of neurogenesis in the sea urchin embryo from blastula stage (just before neural progenitors begin their specifca- tion sequence) through pluteus larval stage (when much of the nervous system has been patterned). Among those 21 gene expression patterns, we report expression of 11 transcription factors and 2 axon guidance genes, each expressed in discrete domains in the neuroectoderm or in the endoderm.
    [Show full text]
  • Genome-Wide Analysis of the Mouse Lung Transcriptome Reveals
    Alberts et al. Respiratory Research 2011, 12:61 http://respiratory-research.com/content/12/1/61 RESEARCH Open Access Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures Rudi Alberts1,LuLu2,3, Robert W Williams2 and Klaus Schughart1* Abstract Background: The lung is critical in surveillance and initial defense against pathogens. In humans, as in mice, individual genetic differences strongly modulate pulmonary responses to infectious agents, severity of lung disease, and potential allergic reactions. In a first step towards understanding genetic predisposition and pulmonary molecular networks that underlie individual differences in disease vulnerability, we performed a global analysis of normative lung gene expression levels in inbred mouse strains and a large family of BXD strains that are widely used for systems genetics. Our goal is to provide a key community resource on the genetics of the normative lung transcriptome that can serve as a foundation for experimental analysis and allow predicting genetic predisposition and response to pathogens, allergens, and xenobiotics. Methods: Steady-state polyA+ mRNA levels were assayed across a diverse and fully genotyped panel of 57 isogenic strains using the Affymetrix M430 2.0 array. Correlations of expression levels between genes were determined. Global expression QTL (eQTL) analysis and network covariance analysis was performed using tools and resources in GeneNetwork http://www.genenetwork.org. Results: Expression values were highly variable across strains and in many cases exhibited a high heri-tability factor. Several genes which showed a restricted expression to lung tissue were identified. Using correlations between gene expression values across all strains, we defined and extended memberships of several important molecular networks in the lung.
    [Show full text]
  • Molecular Distinctions Between Pediatric and Adult Mature B-Cell Non-Hodgkin Lymphomas Identified Through Genomic Profiling
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Public Health Resources Public Health Resources 4-19-2012 Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling Karen Deffenbacher University of Nebraska Medical Center, Omaha Javeed Iqbal University of Nebraska Medical Center, Omaha Warren Sanger University of Nebraska Medical Center, Omaha Yulei Shen University of Nebraska Medical Center, Omaha Cynthia Lachel University of Nebraska Medical Center, Omaha See next page for additional authors Follow this and additional works at: https://digitalcommons.unl.edu/publichealthresources Part of the Public Health Commons Deffenbacher, Karen; Iqbal, Javeed; Sanger, Warren; Shen, Yulei; Lachel, Cynthia; Liu, Zhongfeng; Liu, Yanyan; Lim, Megan; Perkins, Sherrie; Fu, Kai; Smith, Lynette; Lynch, James; Staudt, Louis; Rimsza, Lisa M.; Jaffe, Elaine; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Gascoyne, Randy; Cairo, Mitchell; Weisenburger, Dennis; Greiner, Timothy; Gross, Thomas; and Chan, Wing, "Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling" (2012). Public Health Resources. 145. https://digitalcommons.unl.edu/publichealthresources/145 This Article is brought to you for free and open access by the Public Health Resources at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Public Health Resources by an authorized administrator
    [Show full text]
  • Comparative Analysis of the Ubiquitin-Proteasome System in Homo Sapiens and Saccharomyces Cerevisiae
    Comparative Analysis of the Ubiquitin-proteasome system in Homo sapiens and Saccharomyces cerevisiae Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Universität zu Köln vorgelegt von Hartmut Scheel aus Rheinbach Köln, 2005 Berichterstatter: Prof. Dr. R. Jürgen Dohmen Prof. Dr. Thomas Langer Dr. Kay Hofmann Tag der mündlichen Prüfung: 18.07.2005 Zusammenfassung I Zusammenfassung Das Ubiquitin-Proteasom System (UPS) stellt den wichtigsten Abbauweg für intrazelluläre Proteine in eukaryotischen Zellen dar. Das abzubauende Protein wird zunächst über eine Enzym-Kaskade mit einer kovalent gebundenen Ubiquitinkette markiert. Anschließend wird das konjugierte Substrat vom Proteasom erkannt und proteolytisch gespalten. Ubiquitin besitzt eine Reihe von Homologen, die ebenfalls posttranslational an Proteine gekoppelt werden können, wie z.B. SUMO und NEDD8. Die hierbei verwendeten Aktivierungs- und Konjugations-Kaskaden sind vollständig analog zu der des Ubiquitin- Systems. Es ist charakteristisch für das UPS, daß sich die Vielzahl der daran beteiligten Proteine aus nur wenigen Proteinfamilien rekrutiert, die durch gemeinsame, funktionale Homologiedomänen gekennzeichnet sind. Einige dieser funktionalen Domänen sind auch in den Modifikations-Systemen der Ubiquitin-Homologen zu finden, jedoch verfügen diese Systeme zusätzlich über spezifische Domänentypen. Homologiedomänen lassen sich als mathematische Modelle in Form von Domänen- deskriptoren (Profile) beschreiben. Diese Deskriptoren können wiederum dazu verwendet werden, mit Hilfe geeigneter Verfahren eine gegebene Proteinsequenz auf das Vorliegen von entsprechenden Homologiedomänen zu untersuchen. Da die im UPS involvierten Homologie- domänen fast ausschließlich auf dieses System und seine Analoga beschränkt sind, können domänen-spezifische Profile zur Katalogisierung der UPS-relevanten Proteine einer Spezies verwendet werden. Auf dieser Basis können dann die entsprechenden UPS-Repertoires verschiedener Spezies miteinander verglichen werden.
    [Show full text]
  • 1 Table 1S. Genes Over-Expressed in AILT Vs. Normal T-Lymphocytes
    Table 1S. Genes over-expressed in AILT vs. normal T-lymphocytes (corresponding to CD4+, CD8+ and HLA-DR+ elements) Over-expression (Z Gene Common GeneBank Description score) 9.38 232544_at AU144916 CDNA FLJ11572 fis, clone HEMBA1003373 9.179 220423_at PLA2G2D NM_012400 phospholipase A2, group IID 9.093 211719_x_at FN1 BC005858 fibronectin 1 9.005 204163_at EMILIN1 NM_007046 elastin microfibril interfacer 1 8.642 216442_x_at FN1 AK026737 fibronectin 1 8.552 220690_s_at DKFZp566O084 NM_015510 DKFZP566O084 protein 8.204 210072_at CCL19 U88321 chemokine (CC motif) ligand 19 7.996 230047_at FLJ32810 BF439533 nab67d10.x1 Soares_NSF_F8_9W_OT_PA_P_S1 Homo sapiens cDNA clone IMAGE:3272875 3', mRNA sequence. 7.641 225575_at LIFR AI680541 leukemia inhibitory factor receptor 7.59 215076_s_at COL3A1 AU144167 collagen, type III, alpha 1 (EhlersDanlos syndrome type IV, autosomal dominant) 7.581 204570_at COX7A1 NM_001864 cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) 7.56 217767_at C3 NM_000064 complement component 3 7.411 211981_at COL4A1 NM_001845 collagen, type IV, alpha 1 7.384 204606_at CCL21 NM_002989 chemokine (CC motif) ligand 21 7.384 201162_at IGFBP7 NM_001553 insulinlike growth factor binding protein 7 7.2 208747_s_at C1S M18767 complement component 1, s subcomponent 7.102 203915_at CXCL9 NM_002416 chemokine (CXC motif) ligand 9 6.938 222162_s_at ADAMTS1 AK023795 a disintegrinlike and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1 6.931 205890_s_at UBD NM_006398 ubiquitin D 6.813 222885_at EMCN AF205940 endomucin
    [Show full text]
  • DISCOVERY and CHARACTERIZATION of LONG NON-CODING Rnas in PROSTATE CANCER by John R. Prensner a Dissertation Submitted in Parti
    DISCOVERY AND CHARACTERIZATION OF LONG NON-CODING RNAs IN PROSTATE CANCER by John R. Prensner A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Molecular and Cellular Pathology) in the University of Michigan 2012 Doctoral Committee: Professor Arul M. Chinnaiyan, Chair Professor David Beer Professor Kathleen Cho Professor David Ginsburg Assistant Professor Yali Dou © John R. Prensner All Rights Reserved 2012 ACKNOWLEDGEMENTS This work represents the combined efforts of many talented individuals. First, my mentor, Arul Chinnaiyan, deserves much credit for guiding me through this experience and pushing me to produce the best science that I could. My thesis committee—Kathy Cho, David Beer, David Ginsburg, and Yali Dou—was an integral part of my development and I am truly grateful for their participation in my education. I am also indebted to the many collaborators who have contributed to this work. Foremost, Matthew Iyer has been responsible for much of my progress and has been an invaluable colleague. Saravana M. Dhanasekaran mentored me and taught me much of what I know. Wei Chen has spent countless hours working on these projects. I have also been fortunate to collaborate with Felix Feng, Qi Cao, Alejandro Balbin, Sameek Roychowdhury, Brendan Veeneman, Lalit Patel, Anirban Sahu, Chad Brenner, Irfan Asangani, and Xuhong Cao who have helped to make this thesis possible. I would like to extend my appreciation to my wonderful support network at MCTP and the MSTP office: Karen Giles, Christine Betts, Dianna Banka, Ron Koenig, Ellen Elkin, and Hilkka Ketola, who have been immensely supportive and helpful during my training.
    [Show full text]