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Construction of Stable Mouse Arti Cial Chromosome from Native Mouse
Construction of Stable Mouse Articial Chromosome from Native Mouse Chromosome 10 for Generation of Transchromosomic Mice Satoshi Abe Tottori University Kazuhisa Honma Trans Chromosomics, Inc Akane Okada Tottori University Kanako Kazuki Tottori University Hiroshi Tanaka Trans Chromosomics, Inc Takeshi Endo Trans Chromosomics, Inc Kayoko Morimoto Trans Chromosomics, Inc Takashi Moriwaki Tottori University Shusei Hamamichi Tottori University Yuji Nakayama Tottori University Teruhiko Suzuki Tokyo Metropolitan Institute of Medical Science Shoko Takehara Trans Chromosomics, Inc Mitsuo Oshimura Tottori University Yasuhiro Kazuki ( [email protected] ) Tottori University Research Article Page 1/21 Keywords: mouse articial chromosome (MAC), microcell-mediated chromosome transfer (MMCT), chromosome engineering, transchromosomic (Tc) mouse, humanized model mouse Posted Date: July 9th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-675300/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/21 Abstract Mammalian articial chromosomes derived from native chromosomes have been applied to biomedical research and development by generating cell sources and transchromosomic (Tc) animals. Human articial chromosome (HAC) is a precedent chromosomal vector which achieved generation of valuable humanized animal models for fully human antibody production and human pharmacokinetics. While humanized Tc animals created by HAC vector have attained signicant contributions, there was a potential issue to be addressed regarding stability in mouse tissues, especially highly proliferating hematopoietic cells. Mouse articial chromosome (MAC) vectors derived from native mouse chromosome 11 demonstrated improved stability, and they were utilized for humanized Tc mouse production as a standard vector. In mouse, however, stability of MAC vector derived from native mouse chromosome other than mouse chromosome 11 remains to be evaluated. -
IL21R Expressing CD14+CD16+ Monocytes Expand in Multiple
Plasma Cell Disorders SUPPLEMENTARY APPENDIX IL21R expressing CD14 +CD16 + monocytes expand in multiple myeloma patients leading to increased osteoclasts Marina Bolzoni, 1 Domenica Ronchetti, 2,3 Paola Storti, 1,4 Gaetano Donofrio, 5 Valentina Marchica, 1,4 Federica Costa, 1 Luca Agnelli, 2,3 Denise Toscani, 1 Rosanna Vescovini, 1 Katia Todoerti, 6 Sabrina Bonomini, 7 Gabriella Sammarelli, 1,7 Andrea Vecchi, 8 Daniela Guasco, 1 Fabrizio Accardi, 1,7 Benedetta Dalla Palma, 1,7 Barbara Gamberi, 9 Carlo Ferrari, 8 Antonino Neri, 2,3 Franco Aversa 1,4,7 and Nicola Giuliani 1,4,7 1Myeloma Unit, Dept. of Medicine and Surgery, University of Parma; 2Dept. of Oncology and Hemato-Oncology, University of Milan; 3Hematology Unit, “Fondazione IRCCS Ca’ Granda”, Ospedale Maggiore Policlinico, Milan; 4CoreLab, University Hospital of Parma; 5Dept. of Medical-Veterinary Science, University of Parma; 6Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture; 7Hematology and BMT Center, University Hospital of Parma; 8Infectious Disease Unit, University Hospital of Parma and 9“Dip. Oncologico e Tecnologie Avanzate”, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy ©2017 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2016.153841 Received: August 5, 2016. Accepted: December 23, 2016. Pre-published: January 5, 2017. Correspondence: [email protected] SUPPLEMENTAL METHODS Immunophenotype of BM CD14+ in patients with monoclonal gammopathies. Briefly, 100 μl of total BM aspirate was incubated in the dark with anti-human HLA-DR-PE (clone L243; BD), anti-human CD14-PerCP-Cy 5.5, anti-human CD16-PE-Cy7 (clone B73.1; BD) and anti-human CD45-APC-H 7 (clone 2D1; BD) for 20 min. -
Kinetochore Kinesin CENP-E Is a Processive Bi-Directional Tracker of Dynamic Microtubule Tips
ARTICLES Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips Nikita Gudimchuk1,5, Benjamin Vitre2,5, Yumi Kim2,6, Anatoly Kiyatkin1, Don W. Cleveland2, Fazly I. Ataullakhanov3,4 and Ekaterina L. Grishchuk1,7 During vertebrate mitosis, the centromere-associated kinesin CENP-E (centromere protein E) transports misaligned chromosomes to the plus ends of spindle microtubules. Subsequently, the kinetochores that form at the centromeres establish stable associations with microtubule ends, which assemble and disassemble dynamically. Here we provide evidence that after chromosomes have congressed and bi-oriented, the CENP-E motor continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends. Using a combination of single-molecule approaches and laser trapping in vitro, we demonstrate that once reaching microtubule ends, CENP-E converts from a lateral transporter into a microtubule tip-tracker that maintains association with both assembling and disassembling microtubule tips. Computational modelling of this behaviour supports our proposal that CENP-E tip-tracks bi-directionally through a tethered motor mechanism, which relies on both the motor and tail domains of CENP-E. Our results provide a molecular framework for the contribution of CENP-E to the stability of attachments between kinetochores and dynamic microtubule ends. Accurate chromosome segregation depends on interactions between proportion of lagging chromosomes in anaphase in mouse liver microtubules and the kinetochore, a protein structure localized at cells and embryonic fibroblasts11,17. Fourth, after CENP-E-mediated each centromere1. Initially, kinetochores often attach to the walls congression, CENP-E-dependent localization of protein phosphatase of microtubules with the chromosomes then moving towards a 1 (PP1) to kinetochores is still required for stable microtubule spindle pole in a dynein-dependent manner2,3. -
Organization, Evolution and Function of Alpha Satellite Dna
ORGANIZATION, EVOLUTION AND FUNCTION OF ALPHA SATELLITE DNA AT HUMAN CENTROMERES by M. KATHARINE RUDD Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Advisor: Dr. Huntington F. Willard Department of Genetics CASE WESTERN RESERVE UNIVERSITY January, 2005 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the dissertation of ______________________________________________________ candidate for the Ph.D. degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. 1 Table of Contents Table of contents.................................................................................................1 List of Tables........................................................................................................2 List of Figures......................................................................................................3 Acknowledgements.............................................................................................5 Abstract................................................................................................................6 -
Landscape Genomic Approach to Investigate Genetic Adaptation in South African Indigenous Goat Populations by Khanyisile Mdladla
Landscape genomic approach to investigate genetic adaptation in South African indigenous goat populations by Khanyisile Mdladla Submitted in fulfilment of the academic requirements of Doctor of Philosophy in Genetics School of Life Sciences College of Agriculture, Engineering and Science University of KwaZulu-Natal Pietermaritzburg South Africa December 2016 PREFACE The research contained in this thesis was completed by the candidate while based in the Biotechnology Platform, Agricultural Research Council and the Discipline of Genetics, School of Life Sciences of the College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa. The research was financially supported by University of KwaZulu-Natal, National Research Foundation-Department of Science and Technology (NRF-DST) and the Agricultural Research Council. The contents of this work have not been submitted in any form to another university and, except where the work of others is acknowledged in the text, the results reported are due to investigations by the candidate. _________________________ Signed: Edgar Farai Dzomba Date: _________________________ Signed: Farai Catherine Muchadeyi Date: i DECLARATION 1: PLAGIARISM Note that two declaration sections are required if there are papers emanating from the dissertation/thesis. The first (obligatory) declaration concerns plagiarism and the second declaration specifies your role in the published papers. I, Khanyisile Mdladla declare that: (i) the research reported in this dissertation, except where otherwise indicated or acknowledged, is my original work; (ii) this dissertation has not been submitted in full or in part for any degree or examination to any other university; (iii) this dissertation does not contain other persons’ data, pictures, graphs or other information, unless specifically acknowledged as being sourced from other persons; (iv) this dissertation does not contain other persons’ writing, unless specifically acknowledged as being sourced from other researchers. -
14Q13 Deletions FTNW
14q13 deletions rarechromo.org 14q13 deletions A chromosome 14 deletion means that part of one of the body’s chromosomes (chromosome 14) has been lost or deleted. If the deleted material contains important genes, learning disability, developmental delay and health problems may occur. How serious these problems are depends on how much of the chromosome has been deleted, which genes have been lost and where precisely the deletion is. The features associated with 14q13 deletions vary from person to person, but are likely to include a degree of developmental delay, an unusually small or large head, a raised risk of medical problems and unusual facial features. Genes and chromosomes Our bodies are made up of billions of cells. Most of these cells contain a complete set of thousands of genes that act as instructions, controlling our growth, development and how our bodies work. Inside human cells there is a nucleus where the genes are carried on microscopically small, thread-like structures called chromosomes which are made up p arm p arm of DNA. p arm p arm Chromosomes come in pairs of different sizes and are numbered from largest to smallest, roughly according to their size, from number 1 to number 22. In addition to these so-called autosomal chromosomes there are the sex chromosomes, X and Y. So a human cell has 46 chromosomes: 23 inherited from the mother and 23 inherited from the father, making two sets of 23 chromosomes. A girl has two X chromosomes (XX) while a boy will have one X and one Y chromosome (XY). -
12Q Deletions FTNW
12q deletions rarechromo.org What is a 12q deletion? A deletion from chromosome 12q is a rare genetic condition in which a part of one of the body’s 46 chromosomes is missing. When material is missing from a chromosome, it is called a deletion. What are chromosomes? Chromosomes are the structures in each of the body’s cells that carry genetic information telling the body how to develop and function. They come in pairs, one from each parent, and are numbered 1 to 22 approximately from largest to smallest. Additionally there is a pair of sex chromosomes, two named X in females, and one X and another named Y in males. Each chromosome has a short (p) arm and a long (q) arm. Looking at chromosome 12 Chromosome analysis You can’t see chromosomes with the naked eye, but if you stain and magnify them many hundreds of times under a microscope, you can see that each one has a distinctive pattern of light and dark bands. In the diagram of the long arm of chromosome 12 on page 3 you can see the bands are numbered outwards starting from the point at the top of the diagram where the short and long arms meet (the centromere). Molecular techniques If you magnify chromosome 12 about 850 times, a small piece may be visibly missing. But sometimes the missing piece is so tiny that the chromosome looks normal through a microscope. The missing section can then only be found using more sensitive molecular techniques such as FISH (fluorescence in situ hybridisation, a technique that reveals the chromosomes in fluorescent colour), MLPA (multiplex ligation-dependent probe amplification) and/or array-CGH (microarrays), a technique that shows gains and losses of tiny amounts of DNA throughout all the chromosomes. -
Ce Document Est Le Fruit D'un Long Travail Approuvé Par Le Jury De Soutenance Et Mis À Disposition De L'ensemble De La Communauté Universitaire Élargie
AVERTISSEMENT Ce document est le fruit d'un long travail approuvé par le jury de soutenance et mis à disposition de l'ensemble de la communauté universitaire élargie. Il est soumis à la propriété intellectuelle de l'auteur. Ceci implique une obligation de citation et de référencement lors de l’utilisation de ce document. D'autre part, toute contrefaçon, plagiat, reproduction illicite encourt une poursuite pénale. Contact : [email protected] LIENS Code de la Propriété Intellectuelle. articles L 122. 4 Code de la Propriété Intellectuelle. articles L 335.2- L 335.10 http://www.cfcopies.com/V2/leg/leg_droi.php http://www.culture.gouv.fr/culture/infos-pratiques/droits/protection.htm Ecole Doctorale BioSE (Biologie-Santé-Environnement) Thèse Présentée et soutenue publiquement pour l’obtention du titre de DOCTEUR DE l’UNIVERSITE DE LORRAINE Mention : « Sciences de la Vie et de la Santé » Par Andréa GEOFFROY Conséquences d’une carence en donneurs de méthyles sur la différenciation neuronale et la plasticité : influence d’une supplémentation périnatale sur le développement cérébral. Le 08 Septembre 2015 Membres du jury : Rapporteurs : Pr. Marie-Laure Kottler PU-PH, U1075 INSERM, Caen, France Dr. Patrick Anglard DR, U7364 CNRS, Strasbourg, France Examinateurs : Dr. Hervé Moine DR, CNRS 7104 / INSERM U964, Strasbourg, France Pr. Jean-Louis Guéant PU-PH, U954 INSERM, Nancy, France Dr. Jean-Luc Daval DR, U954 INSERM, Nancy, France Directeur de thèse Dr. Carine Bossenmeyer-Pourié MCU, U954 INSERM, Nancy, France, Co-directeur de thèse Membres invités: Pr. Bruno Charpentier PR, U7365 CNRS, Nancy, France _________________________________________________________________________________ UMR 954 INSERM – «Nutrition, génétique et exposition aux risques environnementaux» 9 avenue de la Forêt de Haye-Faculté de Médecine - 54500 Vandoeuvre-lès-Nancy REMERCIEMENTS Je transmets mes sincères remerciements : A Madame le Professeur Marie-Laure Kottler et à Monsieur le Docteur Patrick Anglard pour avoir accepté d’être rapporteurs pour ma soutenance de thèse. -
The Breakpoint of an Inversion of Chromosome 14 in a T-Cell
Proc. Nati. Acad. Sci. USA Vol. 84, pp. 9069-9073, December 1987 Genetics The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: Sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis (T-cell receptor/ataxia-telangiectasia) R. BAER*t, A. HEPPELLt, A. M. R. TAYLORt, P. H. RABBITTS§, B. BOULLIER§, AND T. H. RABBITTS* *Medical Research Council Laboratory of Molecular Biology and §Ludwig Institute for Cancer Research, Hills Road, Cambridge, CB2 2QH, England; and tUniversity of Birmingham, Cancer Research Laboratories, Department of Cancer Studies, the Medical School, Birmingham, B15 2TJ, England Communicated by C. Milstein, August 11, 1987 (received for review July 13, 1987) ABSTRACT T-cell tumors are characterized by inversions this alternative view. Cytogenetic studies of inv(14) chromo- or translocations of chromosome 14. The breakpoints of these some, by high resolution banding, have identified two differ- karyotypic abnormalities occur in chromosome bands 14qll ent break-reassociation points involved in inv(14) chromo- and 14q32-the same bands in which the T-cell receptor (TCR) somes (15). Notably, the 14q32 breakpoints of nonmalignant a-chain and immunoglobulin heavy chain genes have been clone inversions associated in ataxia-telangiectasia (A-T) are mapped, respectively. Patients with ataxia-telangiectasia are distinct from the 14q32 breakpoints of sporadic inversions particularly prone to development of T-cell chronic lympho- from normal subjects. A similar dichotomy of 14q32 cytic leukemia with such chromosomal abnormalities. We now breakpoints was found in clonal and sporadic t(14;14)(qll;- describe DNA rearrangements of the TCR a-chain gene in an q32) translocations (16). -
Investigation of Differentially Expressed Genes in Nasopharyngeal Carcinoma by Integrated Bioinformatics Analysis
916 ONCOLOGY LETTERS 18: 916-926, 2019 Investigation of differentially expressed genes in nasopharyngeal carcinoma by integrated bioinformatics analysis ZhENNING ZOU1*, SIYUAN GAN1*, ShUGUANG LIU2, RUjIA LI1 and jIAN hUANG1 1Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023; 2Department of Pathology, The Eighth Affiliated hospital of Sun Yat‑sen University, Shenzhen, Guangdong 518033, P.R. China Received October 9, 2018; Accepted April 10, 2019 DOI: 10.3892/ol.2019.10382 Abstract. Nasopharyngeal carcinoma (NPC) is a common topoisomerase 2α and TPX2 microtubule nucleation factor), malignancy of the head and neck. The aim of the present study 8 modules, and 14 TFs were identified. Modules analysis was to conduct an integrated bioinformatics analysis of differ- revealed that cyclin-dependent kinase 1 and exportin 1 were entially expressed genes (DEGs) and to explore the molecular involved in the pathway of Epstein‑Barr virus infection. In mechanisms of NPC. Two profiling datasets, GSE12452 and summary, the hub genes, key modules and TFs identified in GSE34573, were downloaded from the Gene Expression this study may promote our understanding of the pathogenesis Omnibus database and included 44 NPC specimens and of NPC and require further in-depth investigation. 13 normal nasopharyngeal tissues. R software was used to identify the DEGs between NPC and normal nasopharyngeal Introduction tissues. Distributions of DEGs in chromosomes were explored based on the annotation file and the CYTOBAND database Nasopharyngeal carcinoma (NPC) is a common malignancy of DAVID. Gene ontology (GO) and Kyoto Encyclopedia of occurring in the head and neck. It is prevalent in the eastern Genes and Genomes (KEGG) pathway enrichment analysis and southeastern parts of Asia, especially in southern China, were applied. -
SZDB: a Database for Schizophrenia Genetic Research
Schizophrenia Bulletin vol. 43 no. 2 pp. 459–471, 2017 doi:10.1093/schbul/sbw102 Advance Access publication July 22, 2016 SZDB: A Database for Schizophrenia Genetic Research Yong Wu1,2, Yong-Gang Yao1–4, and Xiong-Jian Luo*,1,2,4 1Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China; 2Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China; 3CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China 4YGY and XJL are co-corresponding authors who jointly directed this work. *To whom correspondence should be addressed; Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; tel: +86-871-68125413, fax: +86-871-68125413, e-mail: [email protected] Schizophrenia (SZ) is a debilitating brain disorder with a Introduction complex genetic architecture. Genetic studies, especially Schizophrenia (SZ) is a severe mental disorder charac- recent genome-wide association studies (GWAS), have terized by abnormal perceptions, incoherent or illogi- identified multiple variants (loci) conferring risk to SZ. cal thoughts, and disorganized speech and behavior. It However, how to efficiently extract meaningful biological affects approximately 0.5%–1% of the world populations1 information from bulk genetic findings of SZ remains a and is one of the leading causes of disability worldwide.2–4 major challenge. There is a pressing -
Amplified Fragments of an Autosome-Borne Gene
G C A T T A C G G C A T genes Article Amplified Fragments of an Autosome-Borne Gene Constitute a Significant Component of the W Sex Chromosome of Eremias velox (Reptilia, Lacertidae) Artem Lisachov 1,2,* , Daria Andreyushkova 3, Guzel Davletshina 2,3, Dmitry Prokopov 3 , Svetlana Romanenko 3 , Svetlana Galkina 4 , Alsu Saifitdinova 5 , Evgeniy Simonov 1, Pavel Borodin 2,6 and Vladimir Trifonov 3,6 1 Institute of Environmental and Agricultural Biology (X-BIO), University of Tyumen, Lenina str. 23, 625003 Tyumen, Russia; [email protected] 2 Institute of Cytology and Genetics SB RAS, Acad. Lavrentiev Ave. 10, 630090 Novosibirsk, Russia; [email protected] (G.D.); [email protected] (P.B.) 3 Institute of Molecular and Cellular Biology SB RAS, Acad. Lavrentiev Ave. 8/2, 630090 Novosibirsk, Russia; [email protected] (D.A.); [email protected] (D.P.); [email protected] (S.R.); [email protected] (V.T.) 4 Department of Genetics and Biotechnology, Saint Petersburg State University, Universitetskaya Emb. 7–9, 199034 Saint Petersburg, Russia; [email protected] 5 Department of Human and Animal Anatomy and Physiology, Herzen State Pedagogical University of Russia, Moyka Emb. 48, 191186 Saint Petersburg, Russia; saifi[email protected] 6 Novosibirsk State University, Pirogova str. 3, 630090 Novosibirsk, Russia Citation: Lisachov, A.; * Correspondence: [email protected] Andreyushkova, D.; Davletshina, G.; Prokopov, D.; Romanenko, S.; Abstract: Heteromorphic W and Y sex chromosomes often experience gene loss and heterochroma- Galkina, S.; Saifitdinova, A.; Simonov, tinization, which is frequently viewed as their “degeneration”.