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AIRE Is a Critical Spindle-Associated Protein in Embryonic Stem Cells Bin Gu1, Jean-Philippe Lambert2, Katie Cockburn1, Anne-Claude Gingras2,3, Janet Rossant1,3*
RESEARCH ARTICLE AIRE is a critical spindle-associated protein in embryonic stem cells Bin Gu1, Jean-Philippe Lambert2, Katie Cockburn1, Anne-Claude Gingras2,3, Janet Rossant1,3* 1Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada; 2Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Toronto, Canada; 3Department of Molecular Genetics, University of Toronto, Toronto, Canada Abstract Embryonic stem (ES) cells go though embryo-like cell cycles regulated by specialized molecular mechanisms. However, it is not known whether there are ES cell-specific mechanisms regulating mitotic fidelity. Here we showed that Autoimmune Regulator (Aire), a transcription coordinator involved in immune tolerance processes, is a critical spindle-associated protein in mouse ES(mES) cells. BioID analysis showed that AIRE associates with spindle-associated proteins in mES cells. Loss of function analysis revealed that Aire was important for centrosome number regulation and spindle pole integrity specifically in mES cells. We also identified the c-terminal LESLL motif as a critical motif for AIRE’s mitotic function. Combined maternal and zygotic knockout further revealed Aire’s critical functions for spindle assembly in preimplantation embryos. These results uncovered a previously unappreciated function for Aire and provide new insights into the biology of stem cell proliferation and potential new angles to understand fertility defects in humans carrying Aire mutations. DOI: 10.7554/eLife.28131.001 *For correspondence: janet. [email protected] Introduction Competing interests: The Self-renewal capability, defined as the ability of cells to proliferate while sustaining differentiation authors declare that no potential, is one of the defining features of stem cells (Martello and Smith, 2014). -
An Interview with Maria Leptin
Disease Models & Mechanisms 3, 136-137 (2010) doi:10.1242/dmm.005454 A MODEL FOR LIFE © 2010. Published by The Company of Biologists Ltd Embracing new ideas: an interview with Maria Leptin Maria Leptin works simultaneously in the independent fields of immunology and development. She is the new director of the European Molecular Biology Organization (EMBO) and runs a laboratory in Heidelberg, as well as one in Cologne. Here, she describes how she moved between fields and some of the mechanisms that she believes foster creative science. aria Leptin is not afraid to At that time, developmental biology was accept new challenges. Her beginning to use new molecular techniques early postgraduate work such as chromosome walking, which was in immunology and her allowed researchers to clone genes with recent work uses the ze- known locations, and other tools to under- brafishM as a model organism to understand stand genetics that were just becoming es- host-pathogen interactions. During the tablished. I was interested in a number of time in between, she switched both her re- things like transcription and gene regula- search focus and the model organism that tion in general, as well as the field of she used. As a group leader at the Max Drosophila development. I ended up de- DMM Planck Institute in Tübingen, she uncovered ciding spontaneously to join a lab working some of the pathways that regulate tissue on fly development at the MRC Laboratory differentiation and morphology during of Molecular Biology (LMB) in Cambridge, Drosophila development. Recent work although I originally hadn’t applied to this from her lab shows important similarities in group. -
Beacon in Developmental Biology
NEWS Beacon in developmental biology n Cite as: CMAJ 2017 October 16;189:E1298-9. doi: 10.1503/cmaj.109-5460 Posted on cmajnews.com on September 27, 2017. he identification of Gurdon, whom some people the genes responsi- may know recently received ble for controlling the Nobel Prize for his work Tcellular fate and embryonic cloning frogs; undertaking development in mice has research that demonstrates made Dr. Janet Rossant a that all of development is beacon in the field of written in our genes, and all developmental biology. of our cells contain DNA that Her work pioneered tech- has that information, yet niques that allowed genes somehow during develop- to be altered within ment, different genes are embryos. It also acceler- turned on and differentiation ated avenues in the fields occurs. That’s what really of stem cell biology and turned me on to the underly- regenerative medicine. ing problem of ‘how do we She was awarded the get from a fertilized egg to an 2015 Canada Gairdner organism?’ John is the per- Wightman Award, pre- son who really turned me on sented annually to a Cana- to that question and he has dian who has demon- been pursuing it ever since strated outstanding and so have I.” leadership in medicine and medical science. Rossant For the diverse audience was recognized “for her who read CMAJ, can you outstanding contributions explain what stem cells to developmental biology are? and for her exceptional “Stem cells are cells that international leadership in have the ability to self- stem cell biology and pol- renew, make endless copies icy-making, and in advanc- of themselves and yet also ing research programs for retain the potential to differ- children’s illnesses.” Courtesy of Dr. -
And Short‐Term Outcomes in Renal Allografts with Deceased Donors
Received: 30 May 2017 | Revised: 28 October 2017 | Accepted: 13 November 2017 DOI: 10.1111/ajt.14594 ORIGINAL ARTICLE Long- and short- term outcomes in renal allografts with deceased donors: A large recipient and donor genome- wide association study Maria P. Hernandez-Fuentes1 | Christopher Franklin2 | Irene Rebollo-Mesa1 | Jennifer Mollon1,33 | Florence Delaney1,3 | Esperanza Perucha1 | Caragh Stapleton6 | Richard Borrows4 | Catherine Byrne5 | Gianpiero Cavalleri6 | Brendan Clarke7 | Menna Clatworthy8 | John Feehally9 | Susan Fuggle10 | Sarah A. Gagliano11 | Sian Griffin12 | Abdul Hammad13 | Robert Higgins14 | Alan Jardine15 | Mary Keogan31 | Timothy Leach16 | Iain MacPhee17 | Patrick B. Mark15 | James Marsh18 | Peter Maxwell19 | William McKane20 | Adam McLean21 | Charles Newstead22 | Titus Augustine23 | Paul Phelan24 | Steve Powis25 | Peter Rowe26 | Neil Sheerin27 | Ellen Solomon28 | Henry Stephens24 | Raj Thuraisingham29 | Richard Trembath28 | Peter Topham9 | Robert Vaughan30 | Steven H. Sacks1,3 | Peter Conlon6,31 | Gerhard Opelz32 | Nicole Soranzo2,33 | Michael E. Weale28 | Graham M. Lord1,3 | for the United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3 1King’s College London, MRC Centre for Transplantation, London, UK 2Welcome Trust Sanger Institute, Human Genetics, Cambridge, UK 3NIHR Biomedical Research Centre at Guy’s and St Thomas’, NHS Foundation Trust and King’s College London, London, UK 4Renal Institute of Birmingham, Department of Nephrology and Transplantation, -
A Genome-Wide Meta-Analysis Yields 46 New Loci Associating with Biomarkers of Iron Homeostasis
A Genome-Wide Meta-Analysis Yields 46 New Loci Associating with Biomarkers of Iron Homeostasis Bell, Steven ; Rigas, Andreas S. ; Magnusson, Magnus K. ; Ferkingstad, Egil ; Allara, Elias ; Bjornsdottir, Gyda ; Ramond, Anna ; Sørensen, Erik; Halldorsson, Gisli H. ; Paul, Dirk S. ; Burgdorf, Kristoffer Sølvsten; Eggertsson, Hanne P. ; Howson, Joanna M. M. ; Thørner, Lise W. ; Kristmundsdottir, Snaedis ; Astle, William J. ; Erikstrup, Christian; Sigurdsson, Jon K. ; Vukovic, Dragana; Dinh, Khoa M. ; Tragante, Vinicius ; Surendran, Praveen ; Pedersen, Ole Birger; Vidarsson, Brynja ; Jiang, Tao; Paarup, Helene M.; Onundarson, Pall T. ; Akbari, Parsa ; Nielsen, Kaspar René; Lund, Sigrun H. ; Juliusson, Kristinn ; Magnusson, Magnus I. ; Frigge, Michael L. ; Oddsson, Asmundur ; Olafsson, Isleifur ; Kaptoge, Stephen ; Hjalgrim, Henrik; Runarsson, Gudmundur ; Wood, Angela M. ; Jonsdottir, Ingileif ; Folkmann Hansen, Thomas; Sigurdardottir, Olof ; Stefansson, Hreinn ; Rye, David ; Andersen, Steffen; Banasik, Karina; Brunak, Søren; Burgdorf, Kristoffer ; Erikstrup, Christian; Jemec, Gregor Borut Ernst; Jennum, Poul; Johanssond, Pär I.; Nyegaard, Mette; Petersen, Mikkel; Werge, Thomas; Peters, James E. ; Westergaard, David; Holm, Hilma ; Soranzo, Nicole ; Thorleifsson, Gudmar ; Ouwehand, Willem H. ; Thorsteinsdottir, Unnur ; Roberts, David J. ; Sulem, Patrick; Butterworth, Adam S. ; Gudbjartsson, Daniel F. ; Danesh, John ; Brunak, Søren; Angelantonio, Emanuele Di ; Ullum, Henrik; Stefansson, Kari Document Version Final published version Published in: Communications Biology DOI: 10.1038/s42003-020-01575-z Publication date: 2021 License CC BY Citation for published version (APA): Bell, S., Rigas, A. S., Magnusson, M. K., Ferkingstad, E., Allara, E., Bjornsdottir, G., Ramond, A., Sørensen, E., Halldorsson, G. H., Paul, D. S., Burgdorf, K. S., Eggertsson, H. P., Howson, J. M. M., Thørner, L. W., Kristmundsdottir, S., Astle, W. J., Erikstrup, C., Sigurdsson, J. -
A Computational and Evolutionary Approach to Understanding Cryptic Unstable Transcripts in Yeast
A Computational and Evolutionary Approach to Understanding Cryptic Unstable Transcripts in Yeast By Jessica M. Vera B.S. University of Wisconsin-Madison, 2007 A thesis submitted to the Faculty of the Graduate School in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Molecular, Cellular, and Developmental Biology 2015 This thesis entitled: A Computational and Evolutionary Approach to Understanding Cryptic Unstable Transcripts in Yeast written by Jessica M. Vera has been approved for the Department of Molecular, Cellular, and Developmental Biology Tom Blumenthal Robin Dowell Date The final copy of this thesis has been examined by the signatories, and we find that both the content and the form meet acceptable presentation standards of scholarly work in the above mentioned discipline iii Vera, Jessica M. (Ph.D., Molecular, Cellular and Developmental Biology) A Computational and Evolutionary Approach to Understanding Cryptic Unstable Transcripts in Yeast Thesis Directed by Robin Dowell Cryptic unstable transcripts (CUTs) are a largely unexplored class of nuclear exosome degraded, non-coding RNAs in budding yeast. It is highly debated whether CUT transcription has a functional role in the cell or whether CUTs represent noise in the yeast transcriptome. I sought to ascertain the extent of conserved CUT expression across a variety of Saccharomyces yeast strains to further understand and characterize the nature of CUT expression. To this end I designed a Hidden Markov Model (HMM) to analyze strand-specific RNA sequencing data from nuclear exosome rrp6Δ mutants to identify and compare CUTs in four different yeast strains: S288c, Σ1278b, JAY291 (S.cerevisiae) and N17 (S.paradoxus). -
Methodology for Predicting Semantic Annotations of Protein Sequences by Feature Extraction Derived of Statistical Contact Potentials and Continuous Wavelet Transform
Universidad Nacional de Colombia Sede Manizales Master’s Thesis Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform Author: Supervisor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez A thesis submitted in fulfillment of the requirements for the degree of Master’s on Engineering - Industrial Automation in the Department of Electronic, Electric Engineering and Computation Signal Processing and Recognition Group June 2014 Universidad Nacional de Colombia Sede Manizales Tesis de Maestr´ıa Metodolog´ıapara predecir la anotaci´on sem´antica de prote´ınaspor medio de extracci´on de caracter´ısticas derivadas de potenciales de contacto y transformada wavelet continua Autor: Tutor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez Tesis presentada en cumplimiento a los requerimientos necesarios para obtener el grado de Maestr´ıaen Ingenier´ıaen Automatizaci´onIndustrial en el Departamento de Ingenier´ıaEl´ectrica,Electr´onicay Computaci´on Grupo de Procesamiento Digital de Senales Enero 2014 UNIVERSIDAD NACIONAL DE COLOMBIA Abstract Faculty of Engineering and Architecture Department of Electronic, Electric Engineering and Computation Master’s on Engineering - Industrial Automation Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform by Gustavo Alonso Arango Argoty In this thesis, a method to predict semantic annotations of the proteins from its primary structure is proposed. The main contribution of this thesis lies in the implementation of a novel protein feature representation, which makes use of the pairwise statistical contact potentials describing the protein interactions and geometry at the atomic level. -
University of Cambridge Department of Veterinary Medicine Self
University of Cambridge Department of Veterinary Medicine Self-Evaluation Report Prepared for the joint visit of The Royal College of Veterinary Surgeons and The European Association of Establishments for Veterinary Education 1 List of Visitors Professor Susan Rhind University of Edinburgh, Chair Mr David Wadsworth RCVS Dr Katharina Stärk Spallek RCVS Professor Laslo Fodor EAEVE Dr Pierre Lekeux EAEVE Co-ordinator Professor John Elmerdahl EAEVE Professor Norman Williamson Australasian Veterinary Boards Council Miss Hannelore De Porte EAEVE-nominated student Mrs Clare Tapsfield-Wright RCVS observer Professor Vinny Naidoo South African Veterinary Council observer Mrs Freda Andrews RCVS staff Mrs Christine Warman RCVS staff 2 CONTENTS List of Visitors ............................................................................................................. 2 INTRODUCTION ........................................................................................................ 5 CHAPTER 1 OBJECTIVES ..................................................................................... 11 1.1 Factual information and overall objectives ................................................... 11 1.2 Comments ................................................................................................... 15 1.3 Suggestions ................................................................................................. 16 CHAPTER 2 ORGANISATION ................................................................................ 17 2.1 Factual information -
EMBO Press Release
EMBO – excellence in the life sciences PRESS RELEASE Embargo: 8 June 2021, 14:00 CEST EMBO announces 64 newly elected members EMBO announces the election of 64 life scientists to its membership. 8 June 2021 – EMBO is pleased to announce that 64 life scientists have been elected to its membership. The new EMBO Members and Associate Members join the community of more than 1,800 leading life scientists. “I am delighted to welcome the new members into our organization and look forward to working with them,” says EMBO Director Maria Leptin. “An election to the EMBO Membership recognizes outstanding achievements in the life sciences. The new members will provide expertise and guidance that will help EMBO to further strengthen its initiatives.” The 64 newly elected members reside in 21 countries: 55 new EMBO Members reside in member states of the EMBC, the intergovernmental organization that funds the major EMBO Programmes and activities. Nine new EMBO Associate Members reside in Argentina, Australia, India, Japan, and the USA. 26 of the new EMBO Members (41%) are women. EMBO Members are actively involved in the organization. They serve on EMBO Council, Committees and Advisory Editorial Boards of EMBO Press journals, evaluate applications for EMBO funding, and mentor early-career scientists. Collectively, they can influence the direction of the life sciences in Europe and beyond. New members are nominated and elected by the existing EMBO Membership; it is not possible to apply to become a member. One election is held each year. The new EMBO Members will be formally welcomed at the annual EMBO Members’ Meeting between 27 and 29 October 2021. -
Endogenous Opioids in the Nucleus Accumbens Promote Approach to High-Fat Food in the Absence of Caloric Need Kevin Caref1, Saleem M Nicola1,2*
RESEARCH ARTICLE Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need Kevin Caref1, Saleem M Nicola1,2* 1Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States; 2Department of Psychiatry, Albert Einstein College of Medicine, Bronx, United States Abstract When relatively sated, people (and rodents) are still easily tempted to consume calorie-dense foods, particularly those containing fat and sugar. Consumption of such foods while calorically replete likely contributes to obesity. The nucleus accumbens (NAc) opioid system has long been viewed as a critical substrate for this behavior, mainly via contributions to the neural control of consumption and palatability. Here, we test the hypothesis that endogenous NAc opioids also promote appetitive approach to calorie-dense food in states of relatively high satiety. We simultaneously recorded NAc neuronal firing and infused a m-opioid receptor antagonist into the NAc while rats performed a cued approach task in which appetitive and consummatory phases were well separated. The results reveal elements of a neural mechanism by which NAc opioids promote approach to high-fat food despite the lack of caloric need, demonstrating a potential means by which the brain is biased towards overconsumption of palatable food. DOI: https://doi.org/10.7554/eLife.34955.001 Introduction *For correspondence: People often seek and consume calorie-dense food in the absence of hunger, and this behavior has [email protected] profound implications for human health. Although preference for sweet and fatty foods may once Competing interests: The have been adaptive, it now very likely contributes to epidemic rates of obesity and diabetes. -
Annual Report Fy 2018 Human Frontier Science Program Organization
APRIL 2017 APRIL 2018 — MARCH 2019 ANNUAL REPORT FY 2018 HUMAN FRONTIER SCIENCE PROGRAM ORGANIZATION The Human Frontier Science Program Organization (HFSPO) is unique, supporting international collaboration to undertake innovative, risky, basic research at the frontier of the life sciences. Special emphasis is given to the support and training of independent young investigators, beginning at the postdoctoral level. The Program is implemented by an international organisation, supported financially by Australia, Canada, France, Germany, India, Italy, Japan, the Republic of Korea, New Zealand, Norway, Singapore, Switzerland, the United Kingdom of Great Britain and Nothern Ireland, the United States of America, and the European Commission. Since 1990, over 7000 researchers from more than 70 countries have been supported. Of these, 28 HFSP awardees have gone on to receive the Nobel Prize. 2 The following documents are available on the HFSP website www.hfsp.org: Joint Communiqués (Tokyo 1992, Washington 1997, Berlin 2002, Bern 2004, Ottawa 2007, Canberra 2010, Brussels 2013, London 2016): https://www.hfsp.org/about/governance/membership Statutes of the International Human Frontier Science Program Organization: https://www.hfsp.org/about/governance/hfspo-statutes Guidelines for the participation of new members in HFSPO: https://www.hfsp.org/about/governance/membership General reviews of the HFSP (1996, 2001, 2006-2007, 2010, 2018): https://www.hfsp.org/about/strategy/reviews Updated and previous lists of awards, including titles and abstracts: -
Balancing Potency and Differentiation in Mouse Embryo-Derived Stem Cells and in Vivo
Balancing potency and differentiation in mouse embryo-derived stem cells and in vivo By Anne Christine Helness A thesis submitted to Imperial College London for the degree of Doctor of Philosophy Department of Surgery and Oncology Imperial College London September 2011 1 Abstract An inherent challenge for developing organisms is to maintain a critical balance between cell potency and differentiation. This is most obvious in embryonic stem (ES) cells where genetic, epigenetic and cell signalling pathways support ES cell ability to self-renew and to generate all embryonic lineages. Recently, a series of reports revealed how Polycomb-mediated repression might buffer the precocious expression of somatic lineage regulators in ES cells. Notably, these genes carry bivalent chromatin enriched in both repressive (H3K27me3) and permissive (H3K4me2) histone marks. They are targeted by the Polycomb repressive complexes PRC1 (Ring1B) and PRC2, which mediates H3K27me3 and assemble poised RNA polymerase II (RNAP II), conferring silencing of loci primed for future activation (or repression) upon ES cell differentiation. During early development the transition from morula to blastocyst is the starting point for lineage segregation into the inner cell mass (ICM) and trophectoderm (TE). ES cells are derived from the ICM and are pluripotent. By contrast, TE-derived trophoblast stem (TS) cells are multipotent and contribute solely to placenta formation in vivo. To address whether ES cells epigenetic features are unique attributes of pluripotent cells in the early embryo, we compared the epigenetic status of key developmental genes in blastocyst-derived stem cells and in vivo. We provide direct evidence that bivalent histone markings operate in vivo from the eight-cell up to the blastocyst stage.