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Sample records for jen-kun lin editor

  1. New Editor

    NASA Astrophysics Data System (ADS)

    2007-03-01

    It is an honour and a challenge to take up the editorship of the Messenger at this time of ESO's expanding role in European and worldwide astronomy. In order to mark the change, we have made a few adjustments to the appearance without departing from the overall style that Peter Shaver had evolved during his term as editor. I would like to thank Peter for gen-tly coaching me into the position and Jutta Boxheimer, the technical editor, for the high quality of the layout.

  2. Editor's note

    NASA Astrophysics Data System (ADS)

    Umapathy, Siva

    2017-01-01

    This is an editor's note related to the publication 'Biologically active and thermally stable polymeric Schiff base and its metal polychelates: Their synthesis and spectral aspects' by Raza Rasool and Sumaiya Hasnain, which appeared in Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 148 (2015) 435-443.

  3. TOAD Editor

    NASA Technical Reports Server (NTRS)

    Bingle, Bradford D.; Shea, Anne L.; Hofler, Alicia S.

    1993-01-01

    Transferable Output ASCII Data (TOAD) computer program (LAR-13755), implements format designed to facilitate transfer of data across communication networks and dissimilar host computer systems. Any data file conforming to TOAD format standard called TOAD file. TOAD Editor is interactive software tool for manipulating contents of TOAD files. Commonly used to extract filtered subsets of data for visualization of results of computation. Also offers such user-oriented features as on-line help, clear English error messages, startup file, macroinstructions defined by user, command history, user variables, UNDO features, and full complement of mathematical statistical, and conversion functions. Companion program, TOAD Gateway (LAR-14484), converts data files from variety of other file formats to that of TOAD. TOAD Editor written in FORTRAN 77.

  4. WRR editors

    NASA Astrophysics Data System (ADS)

    New editors of AGU's Water Resources Research journal will be Soroosh Sorooshian and Roger E. Smith.Soroosh Sorooshian was born in Kerman, Iran. He received his B.S. degree in mechanical engineering from California State Polytechnic University, San Luis Obispo, in 1971. He received his M.S. degree in operations research in 1973 and his Ph.D. degree in water resources systems engineering in 1978, both from the University of California, Los Angeles.

  5. MPS Editor

    NASA Technical Reports Server (NTRS)

    Mathews, William S.; Liu, Ning; Francis, Laurie K.; OReilly, Taifun L.; Schrock, Mitchell; Page, Dennis N.; Morris, John R.; Joswig, Joseph C.; Crockett, Thomas M.; Shams, Khawaja S.

    2011-01-01

    Previously, it was time-consuming to hand-edit data and then set up simulation runs to find the effect and impact of the input data on a spacecraft. MPS Editor provides the user the capability to create/edit/update models and sequences, and immediately try them out using what appears to the user as one piece of software. MPS Editor provides an integrated sequencing environment for users. It provides them with software that can be utilized during development as well as actual operations. In addition, it provides them with a single, consistent, user friendly interface. MPS Editor uses the Eclipse Rich Client Platform to provide an environment that can be tailored to specific missions. It provides the capability to create and edit, and includes an Activity Dictionary to build the simulation spacecraft models, build and edit sequences of commands, and model the effects of those commands on the spacecraft. MPS Editor is written in Java using the Eclipse Rich Client Platform. It is currently built with four perspectives: the Activity Dictionary Perspective, the Project Adaptation Perspective, the Sequence Building Perspective, and the Sequence Modeling Perspective. Each perspective performs a given task. If a mission doesn't require that task, the unneeded perspective is not added to that project's delivery. In the Activity Dictionary Perspective, the user builds the project-specific activities, observations, calibrations, etc. Typically, this is used during the development phases of the mission, although it can be used later to make changes and updates to the Project Activity Dictionary. In the Adaptation Perspective, the user creates the spacecraft models such as power, data store, etc. Again, this is typically used during development, but will be used to update or add models of the spacecraft. The Sequence Building Perspective allows the user to create a sequence of activities or commands that go to the spacecraft. It provides a simulation of the activities and

  6. Journal Editors Celebrated at Editors' Evening

    NASA Astrophysics Data System (ADS)

    Panning, Jeanette

    2014-02-01

    At the Fall Meeting, the premiere social event for AGU's many journal editors is the annual Editors' Evening, an opportunity for members to celebrate and to recognize the efforts of retiring editors. At the event, AGU president Carol Finn welcomed all those in attendance and thanked them for volunteering their time for the benefit of AGU and the wider research community.

  7. DNAAlignEditor: DNA alignment editor tool

    PubMed Central

    Sanchez-Villeda, Hector; Schroeder, Steven; Flint-Garcia, Sherry; Guill, Katherine E; Yamasaki, Masanori; McMullen, Michael D

    2008-01-01

    Background With advances in DNA re-sequencing methods and Next-Generation parallel sequencing approaches, there has been a large increase in genomic efforts to define and analyze the sequence variability present among individuals within a species. For very polymorphic species such as maize, this has lead to a need for intuitive, user-friendly software that aids the biologist, often with naïve programming capability, in tracking, editing, displaying, and exporting multiple individual sequence alignments. To fill this need we have developed a novel DNA alignment editor. Results We have generated a nucleotide sequence alignment editor (DNAAlignEditor) that provides an intuitive, user-friendly interface for manual editing of multiple sequence alignments with functions for input, editing, and output of sequence alignments. The color-coding of nucleotide identity and the display of associated quality score aids in the manual alignment editing process. DNAAlignEditor works as a client/server tool having two main components: a relational database that collects the processed alignments and a user interface connected to database through universal data access connectivity drivers. DNAAlignEditor can be used either as a stand-alone application or as a network application with multiple users concurrently connected. Conclusion We anticipate that this software will be of general interest to biologists and population genetics in editing DNA sequence alignments and analyzing natural sequence variation regardless of species, and will be particularly useful for manual alignment editing of sequences in species with high levels of polymorphism. PMID:18366684

  8. Boerhaave: Author and Editor *

    PubMed Central

    Lindeboom, G. A.

    1974-01-01

    The many facets of Herman Boerhaave's life are presented. He was a renowned teacher, physician, author, and editor. Discussed here are his activities as cataloger of the Vossius Collection, author of books on chemistry, botany, and medicine, and as editor of works by Vesalius and early Greek medical writers. Printing and bookselling in Leiden during Boerhaave's era are described. Images PMID:4596962

  9. [Research progress of Lin28 function].

    PubMed

    Shen, Honghong; Niu, Yun

    2014-09-01

    As a highly conserved RNA binding protein, Lin28 is a specific post-transcriptional inhibitor of let-7 biogenesis and can inhibit the let-7 processing and synthesis. Lin28 is involved in the stem cell proliferation and promote the rapid growth of embryonic stem cells. Lin28 plays an important role in the formation of tumor stem cells. Overexpression of Lin28 promotes the tumor cell proliferation and is associated with advanced human cancers. Lin28 can promote tissue repair.

  10. Editors' Fall Picks

    ERIC Educational Resources Information Center

    Hoffert, Barbara; Heilbrun, Margaret; Kuzyk, Raya; Kim, Ann; McCormack, Heather; Katterjohn, Anna; Burns, Ann; Williams, Wilda

    2008-01-01

    From the fall's cascade of great new books, "Library Journal's" editors select their favorites--a dark rendition of Afghan life, a look at the "self-esteem trap," a celebration of Brooklyn activism, and much more.

  11. ISTP CDF Skeleton Editor

    NASA Technical Reports Server (NTRS)

    Chimiak, Reine; Harris, Bernard; Williams, Phillip

    2013-01-01

    Basic Common Data Format (CDF) tools (e.g., cdfedit) provide no specific support for creating International Solar-Terrestrial Physics/Space Physics Data Facility (ISTP/SPDF) standard files. While it is possible for someone who is familiar with the ISTP/SPDF metadata guidelines to create compliant files using just the basic tools, the process is error-prone and unreasonable for someone without ISTP/SPDF expertise. The key problem is the lack of a tool with specific support for creating files that comply with the ISTP/SPDF guidelines. There are basic CDF tools such as cdfedit and skeletoncdf for creating CDF files, but these have no specific support for creating ISTP/ SPDF compliant files. The SPDF ISTP CDF skeleton editor is a cross-platform, Java-based GUI editor program that allows someone with only a basic understanding of the ISTP/SPDF guidelines to easily create compliant files. The editor is a simple graphical user interface (GUI) application for creating and editing ISTP/SPDF guideline-compliant skeleton CDF files. The SPDF ISTP CDF skeleton editor consists of the following components: A swing-based Java GUI program, JavaHelp-based manual/ tutorial, Image/Icon files, and HTML Web page for distribution. The editor is available as a traditional Java desktop application as well as a Java Network Launching Protocol (JNLP) application. Once started, it functions like a typical Java GUI file editor application for creating/editing application-unique files.

  12. A century of editors.

    PubMed

    Riley, R W

    1983-07-08

    They are unalike and far apart, these 13 past editors of The Journal. Between Nathan S. Davis's first issue and William R. Barclay's retirement, there was almost a century of change in medicine, society, the American Medical Association, prose style, and editorial needs. During these years, the editors ranged from the brilliant organizers John B. Hamilton and George H. Simmons to the diligent John H. Hollister and the devoted Johnson F. Hammond. There were editors with the hot determination of James C. Culbertson, John H. Talbott, and Robert H. Moser, and there were those with the cool precision of Austin Smith and Hugh H. Hussey. They varied from Morris Fishbein, who wrote and spoke "with the grade of an eagle in its unhindered soar," to Truman W. Miller, who wrote scarcely a word. Here, briefly, they are together.

  13. PANEL LIBRARY AND EDITOR

    NASA Technical Reports Server (NTRS)

    Raible, E.

    1994-01-01

    The Panel Library and Editor is a graphical user interface (GUI) builder for the Silicon Graphics IRIS workstation family. The toolkit creates "widgets" which can be manipulated by the user. Its appearance is similar to that of the X-Windows System. The Panel Library is written in C and is used by programmers writing user-friendly mouse-driven applications for the IRIS. GUIs built using the Panel Library consist of "actuators" and "panels." Actuators are buttons, dials, sliders, or other mouse-driven symbols. Panels are groups of actuators that occupy separate windows on the IRIS workstation. The application user can alter variables in the graphics program, or fire off functions with a click on a button. The evolution of data values can be tracked with meters and strip charts, and dialog boxes with text processing can be built. Panels can be stored as icons when not in use. The Panel Editor is a program used to interactively create and test panel library interfaces in a simple and efficient way. The Panel Editor itself uses a panel library interface, so all actions are mouse driven. Extensive context-sensitive on-line help is provided. Programmers can graphically create and test the user interface without writing a single line of code. Once an interface is judged satisfactory, the Panel Editor will dump it out as a file of C code that can be used in an application. The Panel Library (v9.8) and Editor (v1.1) are written in C-Language (63%) and Scheme, a dialect of LISP, (37%) for Silicon Graphics 4D series workstations running IRIX 3.2 or higher. Approximately 10Mb of disk space is required once compiled. 1.5Mb of main memory is required to execute the panel editor. This program is available on a .25 inch streaming magnetic tape cartridge in UNIX tar format for an IRIS, and includes a copy of XScheme, the public-domain Scheme interpreter used by the Panel Editor. The Panel Library Programmer's Manual is included on the distribution media. The Panel Library and

  14. MSSP Associate Editors

    NASA Astrophysics Data System (ADS)

    Mottershead, John E.

    2015-08-01

    MSSP is pleased to announce the appointment of three distinguished researchers, Professors Jerome Antoni, Spilios Fassois and Paolo Pennacchi, as Associate Editors. The broad coverage of MSSP research topics demands editorial expertise in several disciplines and the appointment of an editorial team of the highest quality is essential in maintaining and further enhancing the reputation of MSSP as a journal at the forefront of modern experimental mechanics that combines dynamic systems with measurement technology, signal processing and active control. Brief descriptions of the backgrounds and experience of the Associate Editors are provided in the following paragraphs.

  15. PANEL LIBRARY AND EDITOR

    NASA Technical Reports Server (NTRS)

    Raible, E.

    1994-01-01

    The Panel Library and Editor is a graphical user interface (GUI) builder for the Silicon Graphics IRIS workstation family. The toolkit creates "widgets" which can be manipulated by the user. Its appearance is similar to that of the X-Windows System. The Panel Library is written in C and is used by programmers writing user-friendly mouse-driven applications for the IRIS. GUIs built using the Panel Library consist of "actuators" and "panels." Actuators are buttons, dials, sliders, or other mouse-driven symbols. Panels are groups of actuators that occupy separate windows on the IRIS workstation. The application user can alter variables in the graphics program, or fire off functions with a click on a button. The evolution of data values can be tracked with meters and strip charts, and dialog boxes with text processing can be built. Panels can be stored as icons when not in use. The Panel Editor is a program used to interactively create and test panel library interfaces in a simple and efficient way. The Panel Editor itself uses a panel library interface, so all actions are mouse driven. Extensive context-sensitive on-line help is provided. Programmers can graphically create and test the user interface without writing a single line of code. Once an interface is judged satisfactory, the Panel Editor will dump it out as a file of C code that can be used in an application. The Panel Library (v9.8) and Editor (v1.1) are written in C-Language (63%) and Scheme, a dialect of LISP, (37%) for Silicon Graphics 4D series workstations running IRIX 3.2 or higher. Approximately 10Mb of disk space is required once compiled. 1.5Mb of main memory is required to execute the panel editor. This program is available on a .25 inch streaming magnetic tape cartridge in UNIX tar format for an IRIS, and includes a copy of XScheme, the public-domain Scheme interpreter used by the Panel Editor. The Panel Library Programmer's Manual is included on the distribution media. The Panel Library and

  16. LIN28/LIN28B: an emerging oncogenic driver in cancer stem cells.

    PubMed

    Zhou, Jianbiao; Ng, Siok-Bian; Chng, Wee-Joo

    2013-05-01

    LIN28 (LIN28A) is a reprogramming factor and conserved RNA-binding protein. LIN28B is the only homolog of LIN28 in humans, sharing structure and certain function. LIN28/LIN28B has been identified to be overexpressed in a wide range of solid tumors and hematological malignancies. Blockage of let-7 miRNA biogensis and subsequent derepression of let-7 miRNA target genes by LIN28/LIN28B play important roles in cancer progression and metastasis. We will first provide an overview of LIN28/LIN28B gene and protein structures, followed by summary of the studies that showed their aberrant expression in primary human cancers and relevant clinical significance with emphasis on their roles in formation of cancer stem cells. Next, we will highlight the current knowledge of LIN28/LIN28B regulators and molecular mechanisms of LIN28/LIN28B-mediated oncogenesis. The potential medical applications for targeting LIN28/LIN28B will also be discussed in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Editors' Spring Picks

    ERIC Educational Resources Information Center

    Library Journal, 2011

    2011-01-01

    While they do not represent the rainbow of reading tastes American public libraries accommodate, Book Review editors are a wildly eclectic bunch. One look at their bedside tables and ereaders would reveal very little crossover. This article highlights an eclectic array of spring offerings ranging from print books to an audiobook to ebook apps. It…

  18. Editor's message: Student involvement

    Treesearch

    Bill Block

    2012-01-01

    In the initial Editor's Message of this volume, I stated my intent to involve more students in the publication process. A number of people commented on it being a good idea, but only a couple have followed up. One was Paul Krausman, President of The Wildlife Society. We matched graduate students from the University of Montana wildlife program with manuscripts...

  19. Editors' Fall Picks

    ERIC Educational Resources Information Center

    Heilbrun, Margaret; McCormack, Heather; Katterjohn, Anna; Kuzyk, Raya; Roncevic, Mirela; Fox, Bette-Lee; Hoffert, Barbara

    2009-01-01

    "Library Journal's" review editors select fall titles readers won't want to miss--"Waiting on a Train: The Embattled Future of Passenger Rail Service" (James McCommons); "Happy" (Alex Lemon); "Free for All: Joe Papp, the Public, and the Greatest Theater Story Ever Told" (Kenneth Turan & Joseph Papp); "In My Father's Shadow: A Daughter Remembers…

  20. LDAP Browser/Editor

    SciTech Connect

    Gawor, Jarek; Laszewski, Gregor von

    2000-07-18

    The LDAP Browser/Editor provides a user-friendly Java-based interface to LDAP databases with tightly integrated browsing and editing capabilities. Entirely written in Java with help of the JFC (Swingset) and JNDI class libraries. It connects to any X.500, LDAP v2 and v3 servers and supports editing of multiple-value attributes.

  1. Editors' Spring Picks

    ERIC Educational Resources Information Center

    Library Journal, 2011

    2011-01-01

    While they do not represent the rainbow of reading tastes American public libraries accommodate, Book Review editors are a wildly eclectic bunch. One look at their bedside tables and ereaders would reveal very little crossover. This article highlights an eclectic array of spring offerings ranging from print books to an audiobook to ebook apps. It…

  2. WRR editor Ronald Cummings

    NASA Astrophysics Data System (ADS)

    1984-04-01

    It has been nearly a year since Ronald Cummings took over as policy sciences editor of Water Resources Research (WRR), and in that time he has worked to make the journal live up to its role as “an interdisciplinary journal integrating research in the social and natural sciences of water.” Cummings takes the “interdisciplinary” part seriously. “I'd like to see a much broader range of policy issues presented to readers,” he says. “I would hope it would then stimulate interchange between our colleagues concerning evolving issues of the '80s and '90s.”Cummings brings a solid background as a resource economist to his 4-year term as editor, which began last January and runs until December 1987. Cummings succeeds Jared Cohon as policy sciences editor. Stephen J. Burges is the WRR editor for hydrological, physical, chemical, and biological sciences. Now a Professor of Economics and Director of the Program in Natural Resources Economics at the University of New Mexico, Cummings is a past president of the Association of Environmental and Resource Economists. He has been a consultant in matters of water resources management, forestry management, and energy policy for more than a decade, working on projects in both the United States and Latin America. Since joining the faculty at New Mexico in 1975, he has, among other things, worked with engineers at the Los Alamos National Laboratory in developing operation'management models for hot, dry rock geothermal systems.

  3. Editors' Fall Picks

    ERIC Educational Resources Information Center

    Heilbrun, Margaret; McCormack, Heather; Katterjohn, Anna; Kuzyk, Raya; Roncevic, Mirela; Fox, Bette-Lee; Hoffert, Barbara

    2009-01-01

    "Library Journal's" review editors select fall titles readers won't want to miss--"Waiting on a Train: The Embattled Future of Passenger Rail Service" (James McCommons); "Happy" (Alex Lemon); "Free for All: Joe Papp, the Public, and the Greatest Theater Story Ever Told" (Kenneth Turan & Joseph Papp); "In My Father's Shadow: A Daughter Remembers…

  4. Guest Editors' Preface

    NASA Astrophysics Data System (ADS)

    Gille, Peter; Miller, Wolfram; Sangwal, Keshra; Talik, Ewa

    2014-09-01

    The 17th International Conference on Crystal Growth and Epitaxy (ICCGE-17) was held in Warsaw during 11 and 16 August 2013. The contributions during the ICCGE-17 were of three types: Invited lectures, oral presentations and poster presentions. The conference participants were also invited to submit manuscripts based on their contributions for publication in the ICCGE-17 Proceedings volume of Journal of Crystal Growth. The present volume contains manuscripts accepted by the guest editors for this conference volume.

  5. Writers, Editors, and Computer,

    DTIC Science & Technology

    1980-07-01

    future will be for publishers, writers, and editors; it’s usually quite a different matter to make those dreams come true. Occasionally others will say...resources that are completely operational today; there is usually quite a gap between that reality and our dreams ! I’ve spent some time recently trying...AND COMPUTERS. Availability Codes Alo ail Constance U. Greaser list SP~oaJ~\\Head, Publications Department ,tseasy to dream about how marvelous the

  6. Letters to the Editor

    NASA Astrophysics Data System (ADS)

    1997-03-01

    All the Letters to the Editor in this issue are in the same PostScript or PDF file. Contents Criticisms of hands-on pseudoscience David J Fisher 27 Elderberry Road, Cardiff CF5 3RG, UK Measuring varying fields Don Koks Adelaide University, Australia Relativity at A-level: a comment David Sang 3 Ellasdale Road, Bognor Regis, PO21 2SG, UK

  7. ION Configuration Editor

    NASA Technical Reports Server (NTRS)

    Borgen, Richard L.

    2013-01-01

    The configuration of ION (Inter - planetary Overlay Network) network nodes is a manual task that is complex, time-consuming, and error-prone. This program seeks to accelerate this job and produce reliable configurations. The ION Configuration Editor is a model-based smart editor based on Eclipse Modeling Framework technology. An ION network designer uses this Eclipse-based GUI to construct a data model of the complete target network and then generate configurations. The data model is captured in an XML file. Intrinsic editor features aid in achieving model correctness, such as field fill-in, type-checking, lists of valid values, and suitable default values. Additionally, an explicit "validation" feature executes custom rules to catch more subtle model errors. A "survey" feature provides a set of reports providing an overview of the entire network, enabling a quick assessment of the model s completeness and correctness. The "configuration" feature produces the main final result, a complete set of ION configuration files (eight distinct file types) for each ION node in the network.

  8. The Lin28 Expression in Stallion Testes.

    PubMed

    Lee, Geumhui; Jung, Heejun; Yoon, Minjung

    2016-01-01

    The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal. We performed a reverse transcription polymerase chain reaction to confirm the presence of Lin28 mRNA in the testicular tissues and a western blot analysis to verify the cross-reactivity of rabbit Lin28 antibody with horse testicular tissue. For immunohistochemistry, Lin28 (rabbit anti-human), GATA4 (goat anti-human) or DAZL (goat anti-human) antibodies were used. The results of RT-PCR confirmed the expression of Lin28 mRNA in the stallion testes. The western blot analysis showed that the expression of 28 kDa Lin28 protein was localized in the cytoplasm of spermatogonia at both reproductive stages. The numbers of Lin28-positive germ cells per 1000 Sertoli cells in pre- and post-pubertal stages were 253 ± 8.66 and 29.67 ± 2.18, respectively. At both reproductive stages, all Lin28 positive cells showed no co-stained with GATA4 antibody, whereas only some of the Lin28-positive germ cells showed co-staining with DAZL antibody. The results from whole-mount staining showed that the Lin28 expression was limited to Asingle (As) and Apaired (Apr) spermatogonia. In conclusion, Lin28 might be utilized as a molecular marker for undifferentiated spermatogonial stem cells when used with DAZL antibody.

  9. The Lin28 Expression in Stallion Testes

    PubMed Central

    Yoon, Minjung

    2016-01-01

    The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal. We performed a reverse transcription polymerase chain reaction to confirm the presence of Lin28 mRNA in the testicular tissues and a western blot analysis to verify the cross-reactivity of rabbit Lin28 antibody with horse testicular tissue. For immunohistochemistry, Lin28 (rabbit anti-human), GATA4 (goat anti-human) or DAZL (goat anti-human) antibodies were used. The results of RT-PCR confirmed the expression of Lin28 mRNA in the stallion testes. The western blot analysis showed that the expression of 28 kDa Lin28 protein was localized in the cytoplasm of spermatogonia at both reproductive stages. The numbers of Lin28-positive germ cells per 1000 Sertoli cells in pre- and post-pubertal stages were 253 ± 8.66 and 29.67 ± 2.18, respectively. At both reproductive stages, all Lin28 positive cells showed no co-stained with GATA4 antibody, whereas only some of the Lin28-positive germ cells showed co-staining with DAZL antibody. The results from whole-mount staining showed that the Lin28 expression was limited to Asingle (As) and Apaired (Apr) spermatogonia. In conclusion, Lin28 might be utilized as a molecular marker for undifferentiated spermatogonial stem cells when used with DAZL antibody. PMID:27798668

  10. EDITORIAL: Editor's Farewell

    NASA Astrophysics Data System (ADS)

    Hudson, R. P.

    1989-01-01

    The completion of Volume 26, 1989, marked the end of my tenure as Editor of Metrologia. My association with the journal, its parent body the Comité International des Poids et Mesures, its host organization the Bureau International des Poids et Mesures, the publishers Springer-Verlag and last (but by no means least) the Editorial Board, has been a pleasant one and I trust that the subscribers will have found the product to be generally satisfactory. There have been, it is true, some disappointments along the way and I shall mention two of these while expressing the hope that the new Editor will enjoy a greater success in their regard. First is the question of circulation, which has stayed dangerously low, although the shrinkage has tapered off in the most recent years. Because of the narrow public support, the costs of production are relatively high and this, through a consequently high subscription rate, tends to enshrine the unsatisfactory state of affairs. Modest schemes to broaden the journal's appeal and bring in a wider readership have foundered upon the first step, namely, that of procuring from staff members of the national standards laboratories the hoped-for articles which would discuss the state of the art in delivering the highest-quality measurement services to the public. However, some very interesting and bolder schemes are presently under discussion. I had also hoped to leaven the journal's content a little by regularly appearing articles on the latest developments within the great national laboratories. But, as with technical review articles, it has proven very difficult to find the right authors who can also spare the time, and only a few laboratories have found it possible to collaborate. In taking my leave, it remains for me to thank all the contributors, referees and readers for their support, to express the hope of an ever brighter future for Metrologia and to wish to the new Editor, Dr D A Blackburn, a happy and successful tenure.

  11. Letters to the Editor

    NASA Astrophysics Data System (ADS)

    1998-01-01

    All the Letters to the Editor in this issue are in the same PostScript or PDF file. Contents Physics and history Arthur I Miller Department of Science & Technology Studies, University College London, Gower Street, London WC1E 6BT, UK Physics and history: a reply David Miller Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT, UK Cathode rays, the electron and Thomson's discovery John Harris 33 Glentham Road, London SW13 9JD, UK Vectors: swallow them whole! David Wheeler Mahanakorn University of Technology, Bangkok, Thailand

  12. Letters to the Editor

    NASA Astrophysics Data System (ADS)

    1998-03-01

    All the Letters to the Editor in this issue are in the same PostScript or PDF file. Contents Comment on `Magnetic and electric field strengths of high voltage power lines and household appliances' José Luis Giordano Dept. de Ciencia y Tecnología de Materiales y Fluidos, CPSI, Universidad de Zaragoza, Spain Twins paradox S R Carson Norton College, Malton, North Yorkshire, UK On alternative ways of finding the ratio of specific heats of gases Tomas Ficker Physics Department, Technical University of Brno, Czech Republic

  13. Letters to the Editor

    NASA Astrophysics Data System (ADS)

    1998-09-01

    All the Letters to the Editor in this issue are in the same PostScript or PDF file. Contents Science spreadsheets Richard Beare Institute of Education, University of Warwick, Coventry, UK Calculating the `lost energy' Zhang Yongzhao and Zhang Shuyan Police Frontier Guard Patrol Boat Institute, Zhejiang, Ningbo 315801, People's Republic of China Cartesian diver solves the inverse sprinkler problem Boris M Valiyov and Vladimir D Yegorenkov Department of Physics, Kharkov State University, 4 Svobody sq., 310077, Kharkov, Ukraine Update excellence Karen Barker Lytham St Annes, Lancs, UK

  14. Letters to the Editor

    NASA Astrophysics Data System (ADS)

    1997-01-01

    All the Letters to the Editor in this issue are in the same PostScript or PDF file. Contents Software teaching of modular physics: SToMP Stephen Hearn Head of Science, Charterhouse, Godalming, Surrey GU7 2DX Bridging the gap or avoiding a chasm? R W West York Strengths and weaknesses of science John Bausor Christians in Science Education, Edgware, London HA8 6RR Addressing the issues Philip Britton Head of Physics, Leeds Grammar School Modern syllabuses and old textbooks: a useful synthesis Richard Barrass St Mary's College, Doncaster DN1 2ES

  15. [Brief explanation of shi lin (urolithic stranguria)].

    PubMed

    Li, Yuan-yuan

    2010-05-01

    Shi lin (urolithic stranguria) is a kind of stranguria, manifested as pain occurred when pissing and sand-like in the urine, developed from the early concept of shi long. This name of disease was appeared firstly in Shen nong ben cao jing (Shennong's Classic of Materia Medica), and then, the disease name of sha lin, sha shi lin and sha lin were derived from it by the Song Dynasty. It was said that the disease with sha (sand-like) was easy to treat, and with shi (stone-like) was difficult to cure. This disease was also happened in the children, and the reasons were the same with ones of the adult. Furthermore, there was a name of disease, xue sha lin, which was a kind of woman disease and had nothing to do with shi lin.

  16. New TOR editor

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    1984-04-01

    David A. Brooks, associate professor at Texas A&M University's oceanography department, has been appointed editor designate of The Oceanography Report (TOR). He succeeds Arnold L. Gordon of the Lamont-Doherty Geological Observatory. Gordon, who initiated TOR in September 1981, is the new president-elect of the AGU Ocean Sciences Section.Brooks, a physical oceanographer, has been at Texas A&M for 6 years. His research interests include waves and tides, the interaction of waves and currents, Gulf Stream fluctuations, and Gulf of Mexico and Gulf of Maine circulation. Before going to Texas A&M, Brooks was a research associate and graduate faculty member at North Carolina State University in Raleigh.

  17. EDITORIAL: Editor's Introduction

    NASA Astrophysics Data System (ADS)

    Blackburn, D. A.

    1990-01-01

    Since its first issue in 1965 Metrologia has had just three editors, a history of tenure which suggests that those who hold the post find in it sufficient to interest, occupy, challenge and amuse them. I see no reason to doubt that this happy circumstance will continue and look forward to my own period as editor with the intention of retaining, insofar as I am able to interpret them, the best traditions the journal has established so far. As I take up my editorial duties I have become aware that surrounding Metrologia there is a small community of authors, reviewers and readers on whose support the success of the journal entirely depends. It is a community in which the roles change daily with some of its members engaged, even simultaneously, as reader, reviewer and author. I am well aware that the goodwill extended to me as I enter this community is in no small part due the efforts of the outgoing editor, Dr Ralph Hudson, whose easy, engaging and courteous, yet firm, relationship with authors and reviewers emerges clearly from editorial correspondence. I thank him for that he has done and wish him an active and happy retirement. A short foray into the records of Metrologia shows - in the first editorial - that four main kinds of article were originally envisaged: research articles likely to contribute to progress in fundamental scientific measurements, reports of experiments or techniques of particular importance or originality in the area of secondary measurement, articles concerning the decisions of the Comité International des Poids et Mesures, and review articles. No balance was specified but a priority was assigned to articles dealing with fundamental metrology. Of the four categories, the first two represent the core of Metrologia's activity and largely determine its reputation as a publication. For this reason, editorial implementation of the policy set by the CIPM is mainly exercised through the operation of a reviewing system which is intentionally strict

  18. Message from the Editor

    NASA Astrophysics Data System (ADS)

    Stambaugh, Ronald D.

    2014-01-01

    This last year being an odd numbered year, the pages of Nuclear Fusion saw a large influx of expanded papers from the 2012 Fusion Energy Conference in San Diego. Many papers have focused on the scientific and technical challenges posed by ITER. Contributions are steadily increasing from the new superconducting tokamaks in Asia. The ITER Project continues to move ahead. Construction at the Cadarache site is quite remarkable. Buildings completed include the huge Poloidal Field Coils Winding Facility and the Headquarters building, which has been occupied by the ITER staff. Work is progressing on the Assembly building and the Cryostat Workshop. The base of the tokamak complex is being laid. Besides the construction that is taking place and will take place at the site, components from around the world have to navigate the complex route from Marseilles to the site. A test convoy replicating the dimensions and weights of the most exceptional ITER loads successfully traversed that route in 2013. We are pleased to report that the IAEA and ITER have finalized the agreement for ITER authors to publish papers in Nuclear Fusion . Nuclear Fusion is proud to continue its key role in providing the leading forum for the documentation of scientific progress and exchange of research results internationally toward fusion energy. Refereeing The Nuclear Fusion editorial office appreciates greatly the effort made by our referees to sustain the high quality of the journal. Since January 2005, we have been offering the most active referees over the past year a personal subscription to Nuclear Fusion with electronic access for one year, free of charge. We have excluded our Board Members, Guest Editors of special editions and those referees who were already listed in previous years. The following people have been selected: J.M. Canik, Oak Ridge National Laboratory, USA I.T. Chapman, Culham Centre for Fusion Energy, UK L.-G. Eriksson, Commission of the European Communities, Belgium T. Evans

  19. Microbial Properties Database Editor Tutorial

    EPA Science Inventory

    A Microbial Properties Database Editor (MPDBE) has been developed to help consolidate microbial-relevant data to populate a microbial database and support a database editor by which an authorized user can modify physico-microbial properties related to microbial indicators and pat...

  20. Editors in the Electronic Age.

    ERIC Educational Resources Information Center

    Dye, Robert M., Ed.

    Intended for newspaper writers and editors, this collection of articles includes the following titles and authors: "VDTs, TV Haven't Shocked Editors" by Jay Rogers; "Opinions Vary on Electronics' Effect" by Bob Nordyke; "A Few Kind Words for the Censors" by Hugh A. Mulligan; "Those Awards Have Their Limitations" by Larry Fortner; "Obituaries Are…

  1. Microbial properties database editor tutorial

    USDA-ARS?s Scientific Manuscript database

    A Microbial Properties Database Editor (MPDBE) has been developed to help consolidate microbialrelevant data to populate a microbial database and support a database editor by which an authorized user can modify physico-microbial properties related to microbial indicators and pathogens. Physical prop...

  2. Microbial Properties Database Editor Tutorial

    EPA Science Inventory

    A Microbial Properties Database Editor (MPDBE) has been developed to help consolidate microbial-relevant data to populate a microbial database and support a database editor by which an authorized user can modify physico-microbial properties related to microbial indicators and pat...

  3. GUEST EDITORS' INTRODUCTION: Guest Editors' introduction

    NASA Astrophysics Data System (ADS)

    Coulson, Geoff; de Meer, Jan B.

    1997-03-01

    . Their scheme is embedded in an experimental ATM network with the potential for guaranteed QoS. The system features QoS support mechanisms in both the network and the end systems. Of particular interest is reported experience with a dynamic QoS adaptation protocol implemented in the network and based on video scaling techniques and filtering. In summary, this special issue provides an up to date review of approaches to QoS management and their practical realization. Of course, no claim is made as to comprehensiveness, but the chosen papers do serve as a highly representative sample of current directions in QoS research. The editors are very much obliged to all authors, reviewers and publishers. Without their excellent work, and the contribution of their valuable time this special issue would not have been possible.

  4. Different expression patterns of Lin28 and Lin28b in mouse molar development.

    PubMed

    Dong, Ning; Liu, Yan; Zhang, Tiantian; Zhao, Lin; Tian, Jiangang; Ruan, Jianping

    2017-10-01

    The RNA-binding proteins Lin28 and Lin28b are expressed in many developing tissues and are involved in the biosynthesis of the microRNA let-7 family and embryogenesis processes. However, their roles in mammalian tooth development remain ill-defined. The spatiotemporal expressions of Lin28 and Lin28b during mouse molar odontogenesis from day E11.5 to P21 were examined through immunohistochemistry and western blot analysis. Both Lin28 and Lin28b were initially expressed in dental epithelium, but the expression patterns varied thereafter. Lin28 was expressed in tooth germ from early embryonic stages and was consistently expressed in the ameloblasts and odontoblasts throughout all stages of tooth development. However, positive staining of Lin28b gradually faded out with tooth germ development, before finally disappearing in tooth organ cells after birth. These results indicate that Lin28 was spatiotemporally expressed in tooth germ throughout tooth development progression and may play an active role in ameloblast and odontoblast differentiation, as well as matrix secretion and the mineralization of enamel and dentin. Its paralogue Lin28b may have a distinct function in tooth germ formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans Neurons.

    PubMed

    Kirszenblat, Leonie; Pattabiraman, Divya; Hilliard, Massimo A

    2011-09-01

    Nervous system function requires proper development of two functional and morphological domains of neurons, axons and dendrites. Although both these domains are equally important for signal transmission, our understanding of dendrite development remains relatively poor. Here, we show that in C. elegans the Wnt ligand, LIN-44, and its Frizzled receptor, LIN-17, regulate dendrite development of the PQR oxygen sensory neuron. In lin-44 and lin-17 mutants, PQR dendrites fail to form, display stunted growth, or are misrouted. Manipulation of temporal and spatial expression of LIN-44, combined with cell-ablation experiments, indicates that this molecule is patterned during embryogenesis and acts as an attractive cue to define the site from which the dendrite emerges. Genetic interaction between lin-44 and lin-17 suggests that the LIN-44 signal is transmitted through the LIN-17 receptor, which acts cell autonomously in PQR. Furthermore, we provide evidence that LIN-17 interacts with another Wnt molecule, EGL-20, and functions in parallel to MIG-1/Frizzled in this process. Taken together, our results reveal a crucial role for Wnt and Frizzled molecules in regulating dendrite development in vivo.

  6. Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Strassmeier, Klaus G.

    2008-01-01

    As of 2006, Astronomische Nachrichten -- Astronomical Notes has reached its all-time high regarding the ISI journal impact factor, with an impressive increase of 60% compared to 2005. We now rank at position 1,399, as shown in the statistics below. This is solely due to the increased number and quality of published articles: In 2006, Astronomische Nachrichten -- Astronomical Notes published 208 research papers and received 1,033 citations -- five citations per paper on average. In 2007, we have published 177 research papers, and one may be curious to see how their factor will develop. In co-operation with Wiley InterScience we have achieved an average o nline publication time of just 4.5 months. As in the past, publication in Astronomische Nachrichten -- Astronomical Notes} continues to be free of charge. Also, all articles of the first issue of each volume can be downloaded free of charge, as can all articles labelled ``Editor's Choice'', which are additionally featured with a color image on the front cover.

  7. Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Strassmeier, Klaus G.

    2009-01-01

    As of 2007, Astronomische Nachrichten -- Astronomical Notes has reached its all-time high regarding the ISI journal impact factor, with an impressive increase of 60% compared to 2005. We now rank at 1,461, as shown in the statistics below. This is solely due to the increased quality of the published articles: In 2006, Astronomische Nachrichten -- Astronomical Notes published 208 research papers and received 1,033 citations -- five citations per paper on average. In 2007, we have published 177 research papers with roughly the same number of citations. In co-operation with Wiley InterScience we have achieved an average online publication time of just 4.5 months. We hope that the year 2008 will be comparably prosperous. As in the past, publication in Astronomische Nachrichten -- Astronomical Notes continues to be free of charge. Also, all articles of the first issue of each volume can be downloaded free of charge, as can all articles labelled ``Editor's Choice'', which are additionally featured with a color image on the front cover.

  8. [Effects of Lin28a and Lin28b on let-7 family activity].

    PubMed

    Liu, Xue-Rong; Tian, Wen-Hong; Dong, Xiao-Yan; Wu, Xiao-Zhe; Lv, Jian-Xin; Wu, Xiao-Bing

    2011-11-01

    In this report, we study the effects of over-expression of Lin28a and Lin28b on let-7 family activity in HeLaS3. Firstly, we constructed pAAV2neo-Lin28a and pAAV2neo-Lin28b to express Lin28a and Lin28b, respectively. Then, pAAV2neo-Lin28a and pAAV2neo-Lin28b were transfected into HeLaS3, selected with G418 and obtained cell lines, HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b, to express Lin28a and Lin28b stably. Thereafter, we constructed eight plasmid vectors for detection of let-7 family activity based on pAAV2neo-Gluc-(Fluc). These vectors were further packaged into recombinant adeno-associated viral vectors (rAAV) which were used as sensors, nominated as Asensors, to detect inhibition activity of miRNA at post-transcriptional level. Subsequently, with HeLaS3 as a control, we assayed expression levels of Lin28a and Lin28b by Western blot, detected expression levels of let-7 family by QRT-PCR, and tested let-7 family activity by Asensors in HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b. Results demonstrated that both HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b could express Lin28a and Lin28b effectively. Compared with HeLaS3, the expression level of let-7 family except let-7e declined in HeLaS3/pAAV2neo-Lin28a. But declining extent among members of let-7 family was different. The let-7 family activity also decreased while the decreasing extent varied among members. Furthermore, the activity level was not consistent with its expression level for the same member in let-7 family. Compared with HeLaS3, both expression level and activity level of let-7 family in HeLaS3/ pAAV2neo-Lin28b were decreased. However, the decreasing extent of let-7 family expression changes was larger than that of HeLaS3/pAAV2neo-Lin28a while the decreasing extent of activity changes was similar. In this study, we established a method to detect and compare post-transcriptional inhibition level mediated by miRNA complementary targets. We firstly clarified the effect of Lin28a

  9. STE - The Software Tools Editor

    NASA Astrophysics Data System (ADS)

    Software tools is an excellent book written by B. W. Kernighan and P. J. Plauger, published by Addison-Wesley. In it the authors discuss how to write programs that make good tools, and how to program well in the process. One of the tools they develop is a fairly powerful editor, written in Ratfor (a structured form of FORTRAN IV). This program has been implemented on the UCL Starlink VAX (with a few modifications and extensions) and is recommended as the editor to use on the VAX. This note gives a brief introduction to, and description of, the editor which has been abstracted from the book (which you are recommended to buy). There are some short command summary sections at the end of this note. After reading this note you may like to print these short files and use them for reference when using the editor.

  10. PREFACE: Scientific and Publishing Editors

    NASA Astrophysics Data System (ADS)

    2016-02-01

    1.Scientific Editors Section 1: Particle physics Mikhail Skorohvatov - NRC Kurchatov Institute, Moscow, Russia Section 2: Nuclear physics Mikhail Danilov - ITEP NRC Kurchatov Institute, Moscow, Russia Section 3: Cosmic rays Arkady Galper - NRNU MEPhI, Moscow, Russia Anatoly Petrukhin - NRNU MEPhI, Moscow, Russia Section 4: Methods of experimental physics Valery Dmitrenko - NRNU MEPhI, Moscow, Russia 2.Publishing Editors Irene Arkhangelskaja - NRNU MEPhI, Moscow, Russia Pavel Buzhan - NRNU MEPhI, Moscow, Russia

  11. Remarks from a retiring Editor

    NASA Astrophysics Data System (ADS)

    Mansur, Louis K.

    2015-10-01

    At the end of 2015 I plan to step down as Chairman of Editors for the Journal of Nuclear Materials. I use the opportunity to express thoughts that have recurred to me but were muted in comparison with the day to day priorities of editorial work. The most important is that I hold the deepest gratitude for your enduring support- authors, reviewers, readers, the Advisory Editorial Board, and my fellow Editors.

  12. Guest Editor's introduction

    NASA Astrophysics Data System (ADS)

    1996-03-01

    pleasure to be Guest Editor and I look forward to future developments in this growing research area and expositions in Distributed Systems Engineering. Peter G Harrison Imperial College, London

  13. GRL editors: 1986”1988

    NASA Astrophysics Data System (ADS)

    The leading rapid publication journal in the geophysical sciences is seeking candidates to succeed James C.G. Walker, whose term as editor-in-chief ends December 1985. AGU also seeks candidates to succeed the five regional editors: Rob Van der Voo, North America; Gaston J. Kockarts and William Lowrie, Europe; Tetsuya Sato, Asia; and Kurt Lambeck, Australia.AGU President Charles L. Drake has appointed a committee to recommend candidates for the 1986-1988 term. Resumes of those interested in serving in these influential and prestigious posts or letters of recommendation from those who wish to suggest candidates should be sent by February 15, 1985, to GRL Editor Search Committee, American Geophysical Union, 2000 Florida Ave., N.W., Washington, DC 20009.

  14. Message from the Editor

    NASA Astrophysics Data System (ADS)

    Stambaugh, Ronald D.

    2013-01-01

    reviewed five manuscripts in the period November 2011 to December 2012 and provided excellent advice to the authors. We have excluded our Board Members, Guest Editors of special editions and those referees who were already listed in recent years. The following people have been selected: Marina Becoulet, CEA-Cadarache, France Jiaqui Dong, Southwestern Institute of Physics, China Emiliano Fable, Max-Planck-Institut für Plasmaphysik, Germany Ambrogio Fasoli, Ecole Polytechnique Federale de Lausanne, Switzerland Eric Fredrickson, Princeton Plasma Physics Laboratory, USA Manuel Garcia-Munoz, Max-Planck-Institut fuer Plasmaphysik, Germany William Heidbrink, California University, USA Katsumi Ida, National Inst. For Fusion Science, Japan Peter Stangeby, Toronto University, Canada James Strachan, Princeton Plasma Physics Laboratory, USA Victor Yavorskij, Ukraine National Academy of Sciences, Ukraine In addition, there is a group of several hundred referees who have helped us in the past year to maintain the high scientific standard of Nuclear Fusion. At the end of this issue we give the full list of all referees for 2012. Our thanks to them!

  15. Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice.

    PubMed

    Grieco, Anthony; Rzeczkowska, Paulina; Alm, Christina; Palmert, Mark R

    2013-01-30

    Genome-wide association studies recently identified 32 loci that associate with the age at menarche (AAM) in humans. Because the locus most robustly associated with AAM is in/near LIN28B, the goal of this study was to investigate how the Lin28 pathway might modulate pubertal timing by examining expression of Lin28b, and its homologue, Lin28a, across the pubertal transition in female mice. Quantitative reverse-transcriptase PCR data indicate that, prior to the onset of puberty, expression of both Lin28b and Lin28a decreases in the ovary, while expression of only Lin28a decreases in the hypothalamus; the expression of Lin28a increases after the onset of puberty in the pituitary. Immunohistochemistry in ovarian tissue verified that Lin28a protein levels decreased in parallel with gene expression. Although these data do not demonstrate cause and effect, they do suggest that decreased expression of Lin28a/Lin28b may facilitate the transition into puberty, consistent with previous data showing that overexpression of Lin28a in transgenic mice leads to delayed puberty. In addition, although Lin28b and/or Lin28a expression significantly decreased prior to puberty, neither Let-7a nor Let-7g miRNA levels changed significantly, raising the possibility that some effects of Lin28b and Lin28a within the hypothalamic-pituitary-gonadal (HPG) axis may be Let-7 miRNA independent. Subsequent studies, such as tissue and age specific modulation of Lin28b and Lin28a expression, could determine whether the expression patterns observed are responsible for modulating the onset of puberty and delineate further the role of this pathway in the HPG axis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Investigation of Peripubertal Expression of Lin28a and Lin28b in C57BL/6 Female Mice

    PubMed Central

    Grieco, Anthony; Rzeczkowska, Paulina; Alm, Christina; Palmert, Mark R.

    2012-01-01

    Genome-wide association studies recently identified 32 loci that associate with the age at menarche (AAM) in humans. Because the locus most robustly associated with AAM is in/near LIN28B, the goal of this study was to investigate how the Lin28 pathway might modulate pubertal timing by examining expression of Lin28b, and its homologue, Lin28a, across the pubertal transition in female mice. Quantitative reverse-transcriptase PCR data indicate that, prior to the onset of puberty, expression of both Lin28b and Lin28a decreases in the ovary, while expression of only Lin28a decreases in the hypothalamus; the expression of Lin28a increases after the onset of puberty in the pituitary. Immunohistochemistry in ovarian tissue verified that Lin28a protein levels decreased in parallel with gene expression. Although these data do not demonstrate cause and effect, they do suggest that decreased expression of Lin28a/Lin28b may facilitate the transition into puberty, consistent with previous data showing that overexpression of Lin28a in transgenic mice leads to delayed puberty. In addition, although Lin28b and/or Lin28a expression significantly decreased prior to puberty, neither Let-7a nor Let-7g miRNA levels changed significantly, raising the possibility that some effects of Lin28b and Lin28a within the hypothalamic-pituitary-gonadal (HPG) axis may be Let-7 miRNA independent. Subsequent studies, such as tissue and age specific modulation of Lin28b and Lin28a expression, could determine whether the expression patterns observed are responsible for modulating the onset of puberty and delineate further the role of this pathway in the HPG axis. PMID:23138112

  17. New Editors for AGU Journals

    NASA Astrophysics Data System (ADS)

    Panning, Jeanette

    2014-10-01

    John Orcutt, the editor in chief of Earth and Space Science, has filled in his editorial board with Andrea Donnellan (University of Southern California), Jonathan H. Jiang (NASA Jet Propulsion Laboratory, California Institute of Technology), Benoît Pirenne (University of Victoria, BC, Canada), and Frank Vernon (University of California, San Diego).

  18. MAP kinase signaling specificity mediated by the LIN-1 Ets/LIN-31 WH transcription factor complex during C. elegans vulval induction.

    PubMed

    Tan, P B; Lackner, M R; Kim, S K

    1998-05-15

    The let-23 receptor/mpk-1 MAP kinase signaling pathway induces the vulva in C. elegans. We show that MPK-1 directly regulates both the LIN-31 winged-helix and the LIN-1 Ets transcription factors to specify the vulval cell fate. lin-31 and lin-1 act genetically downstream of mpk-1, and both proteins can be directly phosphorylated by MAP kinase. LIN-31 binds to LIN-1, and the LIN-1/LIN-31 complex inhibits vulval induction. Phosphorylation of LIN-31 by MPK-1 disrupts the LIN-1/LIN-31 complex, relieving vulval inhibition. Phosphorylated LIN-31 may also act as a transcriptional activator, promoting vulval cell fates. LIN-31 is a vulval-specific effector of MPK-1, while LIN-1 acts as a general effector. The partnership of tissue-specific and general effectors may confer specificity onto commonly used signaling pathways, creating distinct tissue-specific outcomes.

  19. In vitro expansion of Lin+ and Lin- mononuclear cells from human peripheral blood

    NASA Astrophysics Data System (ADS)

    Norhaiza, H. Siti; Rohaya, M. A. W.; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

    2013-11-01

    Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin-) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin+) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin- cell population. The ability of Lin+ and Lin- to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin+ and Lin- were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin+ mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin- stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation medium support Lin

  20. Research Review: Magazine Editors and Editing Practices.

    ERIC Educational Resources Information Center

    Jolliffe, Lee

    1994-01-01

    Reviews and critiques literature in the subfield of magazine editing research, chiefly biographical studies of individual editors and various types of studies of editorial practices, including surveys, magazine content analyses, and close qualitative examinations of editors' relationships with others. (SR)

  1. Research Review: Magazine Editors and Editing Practices.

    ERIC Educational Resources Information Center

    Jolliffe, Lee

    1994-01-01

    Reviews and critiques literature in the subfield of magazine editing research, chiefly biographical studies of individual editors and various types of studies of editorial practices, including surveys, magazine content analyses, and close qualitative examinations of editors' relationships with others. (SR)

  2. Lin28a regulates germ cell pool size and fertility

    PubMed Central

    Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

  3. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.

    PubMed

    Piskounova, Elena; Polytarchou, Christos; Thornton, James E; LaPierre, Robert J; Pothoulakis, Charalabos; Hagan, John P; Iliopoulos, Dimitrios; Gregory, Richard I

    2011-11-23

    Lin28A and Lin28B selectively block the expression of let-7 microRNAs and function as oncogenes in a variety of human cancers. Lin28A recruits a TUTase (Zcchc11/TUT4) to let-7 precursors to block processing by Dicer in the cell cytoplasm. Here we find that unlike Lin28A, Lin28B represses let-7 processing through a Zcchc11-independent mechanism. Lin28B functions in the nucleus by sequestering primary let-7 transcripts and inhibiting their processing by the Microprocessor. The inhibitory effects of Zcchc11 depletion on the tumorigenic capacity and metastatic potential of human cancer cells and xenografts are restricted to Lin28A-expressing tumors. Furthermore, the majority of human colon and breast tumors analyzed exclusively express either Lin28A or Lin28B. Lin28A is expressed in HER2-overexpressing breast tumors, whereas Lin28B expression characterizes triple-negative breast tumors. Overall our results illuminate the distinct mechanisms by which Lin28A and Lin28B function and have implications for the development of new strategies for cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Oncogenic Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms

    PubMed Central

    Piskounova, Elena; Polytarchou, Christos; Thornton, James E.; Hagan, John P.; LaPierre, Robert J.; Pothoulakis, Charalabos; Iliopoulos, Dimitrios; Gregory, Richard I.

    2011-01-01

    Lin28A and Lin28B selectively block the expression of let-7 microRNAs and function as oncogenes in a variety of human cancers. Lin28A recruits a TUTase (Zcchc11/TUTase4) to let-7 precursors to block processing by Dicer in the cell cytoplasm. Here we find that unlike Lin28A, Lin28B represses let-7 processing through a TUTase-independent mechanism. Lin28B functions in the nucleus by sequestering primary let-7 transcripts and inhibiting their processing by the Microprocessor. The inhibitory effects of Zcchc11 depletion on the tumorigenic capacity and metastatic potential of human cancer cells and xenografts is restricted to Lin28A-expressing tumors. Furthermore, the majority of human colon and breast tumors analyzed exclusively express either Lin28A or Lin28B. Lin28A is expressed in HER2-overexpressing breast tumors while Lin28B expression characterizes triple-negative breast tumors. Overall our results illuminate the distinct mechanisms by which Lin28A and Lin28B function, and have implications for the development of new strategies for cancer therapy. PMID:22118463

  5. SIERRA Editor v. 1.2.1

    SciTech Connect

    Hoffman, Edward; Friedman-Hill, Ernest; Gibson, Marcus; Heinstein, Martin; & Whittford, Greg

    2010-03-24

    The SIERRA Editor is a syntax editor for text-based input decks for the SIERRA modeling and simulations codes. The SIERRA Editor provides color coded syntax, error checking, hyperlink navigation to referenced entities (e.g. functions and materials), and visual verification of mesh entity references (blocks, sidesets, and nodesets). The SIERRA Editor helps modeling and simulation analysts who use the SIERRA codes to produce syntactically correct input decks.

  6. Learning To Use a Text Editor.

    ERIC Educational Resources Information Center

    Beal, Carole R.; Griffin, Elizabeth A.

    Designed to determine how quickly elementary school children can learn to use a text editor and what editing concepts are difficult for them to master, this study presents preliminary data on children's acquisition of text editor skills and on the kinds of revisions they accomplished with the text editor. Observations were made on a total of 25…

  7. Message from the Editor Message from the Editor

    NASA Astrophysics Data System (ADS)

    Thomas, Paul

    2012-04-01

    Whilst travelling to Vienna to hand over the Editorship of Nuclear Fusion to Ron Stambaugh, I jotted down a few ideas to put in a farewell message. Somewhat unsurprisingly, I find them almost identical to the remarks that Chris Schueller made in handing over to me five years ago. Both of us served in this role for five years, which seems like a good timescale to replace presidents and editors alike; just to allow a fresh approach. In addition, since I have been directly involved in ITER, I have found it increasingly difficult, due to time pressure, to give the journal the attention that it deserves. Therefore, I am very pleased that Ron Stambaugh has agreed to take over as Editor. Not only does he bring the experience as a leading figure in the US fusion programme but, in addition, he has all the contacts, worldwide, from his leadership of the ITPA. I am completely assured that the journal is in a highly competent pair of hands. Such a farewell should not lack my heartfelt thanks to all of those who have made being Editor of Nuclear Fusion so enjoyable and stimulating; readership, authors, referees, the Editorial Board and the NF Office alike. I wish Ron all the best for his tenure and have offered such help and support as I am able to give.

  8. Novel LinA Type 3 δ-Hexachlorocyclohexane Dehydrochlorinase

    PubMed Central

    Shrivastava, Nidhi; Prokop, Zbynek

    2015-01-01

    LinA is the first enzyme of the microbial degradation pathway of a chlorinated insecticide, hexachlorocyclohexane (HCH), and mediates the dehydrochlorination of α-, γ-, and δ-HCH. Its two variants, LinA type 1 and LinA type 2, which differ at 10 out of 156 amino acid residues, have been described. Their activities for the metabolism of different HCH isomers differ considerably but overall are high for γ-HCH, moderate for α-HCH, low for δ-HCH, and lacking for β-HCH. Here, we describe the characterization of a new variant of this enzyme, LinA type 3, whose gene was identified from the metagenome of an HCH-contaminated soil sample. Its deduced primary structure in the region spanning amino acid residues 1 to 147 of the protein exhibits 17 and 12 differences from LinA type 1 and LinA type 2, respectively. In addition, the residues GIHFAPS, present at the region spanning residues 148 to 154 in both LinA type 1 and LinA type 2, are deleted in LinA type 3.The activity of LinA type 3 for the metabolism of δ-HCH is several orders of magnitude higher than that of LinA type 1 or LinA type 2 and can be useful for improvement of the metabolism of δ-HCH. PMID:26296732

  9. Lin28: time for tissue repair.

    PubMed

    Reddien, Peter W

    2013-11-07

    Embryos and juveniles in many organisms repair tissue injuries better than adults. In this issue, Shyh-Chang et al. find that postnatal activation of Lin28a, a gene typically active in embryonic development, promotes better than normal tissue repair in mice, including following ear and digit injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Line-Editor Computer Program

    NASA Technical Reports Server (NTRS)

    Scott, Peter J.

    1989-01-01

    ZED editing program for DEC VAX computer simple, powerful line editor for text, program source code, and nonbinary data. Excels in processing of text by use of procedure files. Also features versatile search qualifiers, global changes, conditionals, online help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. Users of Cambridge implementation devised such ZED procedures as chess games, calculators, and programs for evaluating pi. Written entirely in C.

  11. Line-Editor Computer Program

    NASA Technical Reports Server (NTRS)

    Scott, Peter J.

    1989-01-01

    ZED editing program for DEC VAX computer simple, powerful line editor for text, program source code, and nonbinary data. Excels in processing of text by use of procedure files. Also features versatile search qualifiers, global changes, conditionals, online help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. Users of Cambridge implementation devised such ZED procedures as chess games, calculators, and programs for evaluating pi. Written entirely in C.

  12. A Syntax Directed Editor Environment.

    DTIC Science & Technology

    1983-12-05

    Much of his work was based on research by Bruce J. MacLennan of the Naval Postgraduate School (Ref 9) and two of Mister MacLennan’s former thesis...of Defense. Requirement for ADA Programming Suport | .:Environments - Stoneman. Washington, D.C. 1980. • .,6. Feiler , Peter H. and Raul Medina-Mora...1982. (AD-A053032). 9. MacLennan, Bruce J. The Automatic Generation of Syntax-Directed Editors. Naval Postgraduate School, Monterey, CA., 1981. 10

  13. EDITORIAL: Message from the Editor Message from the Editor

    NASA Astrophysics Data System (ADS)

    Thomas, Paul

    2010-02-01

    November 2009 and provided particularly detailed advice to the authors. The other three have been very helpful in 'minority fields'. We have excluded our Board members, Guest Editors of special editions and those referees who were already listed in the last four years. Guest Editors' work on papers submitted to their Special Issues is also excluded from consideration. The following people have been selected: Tomonori Takizuka, JAEA-Naka Fusion Institute, Japan Rudolf Neu, Max-Planck-Institut für Plasmaphysik, Germany Sibylle Guenter, Max-Planck-Institut für Plasmaphysik, Germany Taik-Soo Hahm, Princeton Plasma Physics Laboratory, United States David R. Mikkelsen, Princeton Plasma Physics Laboratory, United States Peter C. de Vries, EURATOM/UKAEA Fusion Association, United Kingdom Yasuhiro Suzuki, National Institute for Fusion Science, Japan Jerzy Wolowski, Institute of Plasma Physics and Laser Microfusion, Poland Tetsuo Tanabe, Kyushu University, Japan Yasuyuki Yagi, National Institute of Advanced Industrial Science and Technology, Japan Congratulations and many, many thanks! The Guest Editors of special editions deserve a special mention for the excellent help that they have given us. They are: Taik-Soo Hahm, Princeton Plasma Physics Laboratory, United States, Special Issue on H-Mode Physics and Transport Barriers Yaroslav Kolesnichenko, Institute for Nuclear Research, Ukraine, Special Issue on Energetic Particles in Magnetic Confinement Systems Kimitaka Itoh, National Institute for Fusion Science, Japan and Howard R. Wilson, University of York, UK, Special Issue on Plasma Instabilities Bernhard Unterberg, Forschungszentrum Juelich, Germany, Special Issue on Stochastic Fusion Plasma In addition, there is a group of several hundred referees who have helped us in the past year to maintain the high scientific standard of Nuclear Fusion. At the end of this issue we give the full list of all referees for 2009. Our thanks to them! Authors The winner of the 2009 Nuclear Fusion

  14. The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction.

    PubMed

    Zou, Yan; Chiu, Hui; Domenger, Dorothée; Chuang, Chiou-Fen; Chang, Chieh

    2012-06-12

    miR-125 microRNAs, such as lin-4 in Caenorhabditis elegans, were among the first microRNAs discovered, are phylogenetically conserved, and have been implicated in regulating developmental timing. Here, we showed that loss-of-function mutations in lin-4 microRNA increased axon attraction mediated by the netrin homolog UNC-6. The absence of lin-4 microRNA suppressed the axon guidance defects of anterior ventral microtubule (AVM) neurons caused by loss-of-function mutations in slt-1, which encodes a repulsive guidance cue. Selective expression of lin-4 microRNA in AVM neurons of lin-4-null animals indicated that the effect of lin-4 on AVM axon guidance was cell-autonomous. Promoter reporter analysis suggested that lin-4 was likely expressed strongly in AVM neurons during the developmental time frame that the axons are guided to their targets. In contrast, the lin-4 reporter was barely detectable in anterior lateral microtubule (ALM) neurons, axon guidance of which is insensitive to netrin. In AVM neurons, the transcription factor LIN-14, a target of lin-4 microRNA, stimulated UNC-6-mediated ventral guidance of the AVM axon. LIN-14 promoted attraction of the AVM axon through the UNC-6 receptor UNC-40 [the worm homolog of vertebrate Deleted in Colorectal Cancer (DCC)] and its cofactor MADD-2, which signals through both the UNC-34 (Ena) and the CED-10 (Rac1) downstream pathways. LIN-14 stimulated UNC-6-mediated axon attraction in part by increasing UNC-40 abundance. Our study indicated that lin-4 microRNA reduced the activity of LIN-14 to terminate UNC-6-mediated axon guidance of AVM neurons.

  15. Donald R. Nielsen New WRR Editor

    NASA Astrophysics Data System (ADS)

    Robb, David W.

    Bridging the gap between the disciplines of engineering and agriculture is a major goal for Water Resources Research (WRR), says Donald R. Nielsen, who was appointed to a 4-year term as WRR editor, effective January 1, 1985. Nielsen succeeds Stephen J. Burges as the WRR editor for hydrology, physical, chemical, and biological sciences. Ronald G. Cummings, at the University of New Mexico, is the WRR editor for policy sciences, including economics, systems analysis, sociology, and law.

  16. Comparison of the expression and function of Lin28A and Lin28B in colon cancer.

    PubMed

    Wang, Tianzhen; He, Yan; Zhu, Yuanyuan; Chen, Mingwei; Weng, Mingjiao; Yang, Chao; Zhang, Yan; Ning, Ning; Zhao, Ran; Yang, Weiwei; Jin, Yinji; Li, Jing; Redpath, Riju James Rajkumar Ezakiel; Zhang, Lei; Jin, Xiaoming; Zhong, Zhaohua; Zhang, Fengmin; Wei, Yunwei; Shen, Guomin; Wang, Dong; Liu, Ying; Wang, Guangyu; Li, Xiaobo

    2016-11-29

    Lin28A and Lin28B are highly conserved RNA binding proteins with similar structure and functions. Recent studies demonstrated that both of them act as oncogenes and promote cancer progression. However, few researches compared the expression and functions of both oncogenes in human malignant tumors at same time. Additionally, although the expression and role of Lin28B in colon cancer is frequently reported, the expression and functions of Lin28A in colon cancer are largely unknown. In this study, we have systematically evaluated the expressional pattern, mutation status and correlation of both Lin28A and Lin28B in colon cancer tissues for the first time, and compared the roles of Lin28A and Lin28B in the proliferation, migration, invasion and apoptosis of colon cancer cells in vitro. We have showed that they are co-expressed and have functional similarities, however, the molecular mechanisms underlying their similar functions may not be identical. This study contributes to clarify the similarities and differences of Lin28A and Lin28B in colon cancer progression.

  17. Comparison of the expression and function of Lin28A and Lin28B in colon cancer

    PubMed Central

    Weng, Mingjiao; Yang, Chao; Zhang, Yan; Ning, Ning; Zhao, Ran; Yang, Weiwei; Jin, Yinji; Li, Jing; Redpath, Riju James Rajkumar Ezakiel; Zhang, Lei; Jin, Xiaoming; Zhong, Zhaohua; Zhang, Fengmin; Wei, Yunwei; Shen, Guomin; Wang, Dong; Liu, Ying; Wang, Guangyu; Li, Xiaobo

    2016-01-01

    Lin28A and Lin28B are highly conserved RNA binding proteins with similar structure and functions. Recent studies demonstrated that both of them act as oncogenes and promote cancer progression. However, few researches compared the expression and functions of both oncogenes in human malignant tumors at same time. Additionally, although the expression and role of Lin28B in colon cancer is frequently reported, the expression and functions of Lin28A in colon cancer are largely unknown. In this study, we have systematically evaluated the expressional pattern, mutation status and correlation of both Lin28A and Lin28B in colon cancer tissues for the first time, and compared the roles of Lin28A and Lin28B in the proliferation, migration, invasion and apoptosis of colon cancer cells in vitro. We have showed that they are co-expressed and have functional similarities, however, the molecular mechanisms underlying their similar functions may not be identical. This study contributes to clarify the similarities and differences of Lin28A and Lin28B in colon cancer progression. PMID:27793004

  18. Lin28 promotes Her2 expression and Lin28/Her2 predicts poorer survival in gastric cancer.

    PubMed

    Wang, Qinchuan; Zhou, Jichun; Guo, Jufeng; Teng, Rongyue; Shen, Jianguo; Huang, Yasheng; Xie, Shuduo; Wei, Qun; Zhao, Wenhe; Chen, Wenjun; Yuan, Xiaoming; Chen, Yongxia; Wang, Linbo

    2014-11-01

    The main purpose of this study is to investigate the interactions between Lin28 and Her2 in gastric cancer. Lin28 and Her2 expression were evaluated in surgically resected samples of 298 gastric cancer patients using immunohistochemical staining. The correlations between Lin28/Her2 expression and clinical variables were retrospectively analyzed. The mRNA level of LIN28 and HER2 was detected by reverse-transcriptase polymerase chain reaction. Among all gastric cancer patients, 33.9% (101/298) were determined as Her2-positive, and 43.0% (128/298) were defined as Lin28-positive. Lin28 was significantly associated with Her2, advanced tumor stage, lesion size, and Ki67 level (p<0.05 for each). Kaplan-Meier analysis illustrated that both Lin28 and Her2 are poor prognostic factors in gastric cancer; Lin28(+)/Her2(+) patients have the poorest survival (median survival = 17 months, p<0.01). Multivariate Cox analysis showed that Lin28 is a significant prognostic factor (hazard ratio (HR) = 1.79, 95% confidence interval (CI) 1.23-2.62). Further stratification analysis indicated that Lin28 may be a prognostic factor in chemotherapy. In vitro data on MKN-28 and MKN-45 cells showed that Lin28 can upregulate Her2 expression at translational level. Both Lin28 and Her2 are poor prognostic factors in gastric cancer. Lin28 may regulate Her2 post-transcriptionally in gastric cancer cells, which indicates it might be a potential target in the treatment of gastric cancer.

  19. EDITORIAL: Message from the Editor Message from the Editor

    NASA Astrophysics Data System (ADS)

    Thomas, Paul

    2011-01-01

    As usual, being an even year, the 23rd IAEA Fusion Energy Conference took place at Daejeon, Korea. The event was notable not just for the quality of the presentations but also for the spectacular opening ceremony, in the presence of the Prime Minister, Kim Hwang-sik. The Prime Minister affirmed the importance of research into fusion energy research and pledged support for ITER. Such political visibility is good news, of course, but it brings with it the obligation to perform. Fortunately, good performance was much in evidence in the papers presented at the conference, of which a significant proportion contain 'ITER' in the title. Given this importance of ITER and the undertaking by the Nuclear Fusion journal to publish papers associated with Fusion Energy Conference presentations, the Nuclear Fusion Editorial Board has decided to adopt a simplified journal scope that encompasses technology papers more naturally. The scope is available from http://iopscience.iop.org/0029-5515/page/Journal%20information but is reproduced here for clarity: Nuclear Fusion publishes articles making significant advances to the field of controlled thermonuclear fusion. The journal scope includes: the production, heating and confinement of high temperature plasmas; the physical properties of such plasmas; the experimental or theoretical methods of exploring or explaining them; fusion reactor physics; reactor concepts; fusion technologies. The key to scope acceptability is now '....significant advances....' rather than any particular area of controlled thermonuclear fusion research. It is hoped that this will make scope decisions easier for the Nuclear Fusion office, the referees and the Editor.The Nuclear Fusion journal has continued to make an important contribution to the research programme and has maintained its position as the leading journal in the field. This is underlined by the fact that Nuclear Fusion has received an impact factor of 4.270, as listed in ISI's 2009 Science Citation

  20. LIN28A expression reduces sickling of cultured human erythrocytes.

    PubMed

    de Vasconcellos, Jaira F; Fasano, Ross M; Lee, Y Terry; Kaushal, Megha; Byrnes, Colleen; Meier, Emily R; Anderson, Molly; Rabel, Antoinette; Braylan, Raul; Stroncek, David F; Miller, Jeffery L

    2014-01-01

    Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes.

  1. Examining Editor-Author Ethics: Real-World Scenarios from Interviews with Three Journal Editors

    ERIC Educational Resources Information Center

    Amare, Nicole; Manning, Alan

    2009-01-01

    Those who submit manuscripts to academic journals may benefit from a better understanding of how editors weigh ethics in their interactions with authors. In an attempt to ascertain and to understand editors' ethics, we interviewed 3 current academic journal editors of technical and/or business communication journals. We asked them about the…

  2. Examining Editor-Author Ethics: Real-World Scenarios from Interviews with Three Journal Editors

    ERIC Educational Resources Information Center

    Amare, Nicole; Manning, Alan

    2009-01-01

    Those who submit manuscripts to academic journals may benefit from a better understanding of how editors weigh ethics in their interactions with authors. In an attempt to ascertain and to understand editors' ethics, we interviewed 3 current academic journal editors of technical and/or business communication journals. We asked them about the…

  3. PROGRAMMABLE DISPLAY PUSHBUTTON LEGEND EDITOR

    NASA Technical Reports Server (NTRS)

    Busquets, A. M.

    1994-01-01

    The Programmable Display Pushbutton (PDP) is a pushbutton device available from Micro Switch which has a programmable 16 x 35 matrix of LEDs on the pushbutton surface. Any desired legends can be displayed on the PDPs, producing user-friendly applications which greatly reduce the need for dedicated manual controls. Because the PDP can interact with the operator, it can call for the correct response before transmitting its next message. It is both a simple manual control and a sophisticated programmable link between the operator and the host system. The Programmable Display Pushbutton Legend Editor, PDPE, is used to create the LED displays for the pushbuttons. PDPE encodes PDP control commands and legend data into message byte strings sent to a Logic Refresh and Control Unit (LRCU). The LRCU serves as the driver for a set of four PDPs. The legend editor (PDPE) transmits to the LRCU user specified commands that control what is displayed on the LED face of the individual pushbuttons. Upon receiving a command, the LRCU transmits an acknowledgement that the message was received and executed successfully. The user then observes the effect of the command on the PDP displays and decides whether or not to send the byte code of the message to a data file so that it may be called by an applications program. The PDPE program is written in FORTRAN for interactive execution. It was developed on a DEC VAX 11/780 under VMS. It has a central memory requirement of approximately 12800 bytes. It requires four Micro Switch PDPs and two RS-232 VAX 11/780 terminal ports. The PDPE program was developed in 1985.

  4. [Report of the editors, 2011].

    PubMed

    García Puig, J; Gaspar Alonso-Vega, G; Ríos Blanco, J J

    2012-01-01

    The editors of Revista Clínica Española (Rev Clin Esp) inform on their editorial activity during the last 12 months (November 2010 to October 2011): (a) Objectives and attainments during 2011, (b) editorial activity, and (c) objectives for 2012. In 2011 we have updated the editorial algorithm (revision by the responsible editor of all manuscripts sent to peer review and incorporated an «editorial coordinator»), we have renovated two advise facilities (editorial and scientific committees), we have created a new section called «monthly e-image», and we have promoted Rev Clin Esp annual prizes. From the first January 2010 to 31(st) October 2011 we handled 422 manuscripts (42,2 manuscripts per month, higher than the 2010 figure of 40,4 manuscript/month). Overall we have accepted 26% (originals, 16%). We asked for 343 revisions and obtained 231 (67%). Seventy two percent of the reviewers sent their comments in less than two weeks. The mean time taken to accept or reject a given manuscript has been 26 days. The mean time taken since a manuscript is received to publication (october, novembrer and december issues) has dropped from 334 days in 2010 to 254 in 2011 (24% decrease). The collaboration with the working groups has reported about 2 published manuscripts per issue. Our objectives for 2012 are: (a) to improve the editorial process; (b) main article translation into English; (c) improve some sections (i.e. clinical conference); (d) estimulate working groups collaboration; and (e) improve continued medical education. Revista Clínica Española is an open forum for all internal medicine specialists. We all have the responsibility to make our journal, each day, better.

  5. EDITORIAL: Message from the Editor

    NASA Astrophysics Data System (ADS)

    Thomas, Paul

    2009-01-01

    Plasmaphysik, Germany) V. Philipps (Forschungszentrum Juelich, Germany) S. Zweben (Princeton Plasma Physics Laboratory, USA) Y. Hirano (National Institute of Advanced Industrial Science and Technology, Japan) Y. Takase (Tokyo University, Japan) In addition there is a group of several hundred referees who have helped us in the past year to maintain the high scientific standard of Nuclear Fusion. At the end of this issue we give the full list of all referees for 2008. Our thanks to them! Authors The winner of the 2007 award was Clemente Angioni for the paper entitled `Density response to central electron heating: theoretical investigations and experimental observations in ASDEX Upgrade' (Nucl. Fusion 44 8277-845). The winner of the 2008 Nuclear Fusion award is Todd Evans et al for the paper `Suppression of large edge localized modes with edge resonant magnetic fields in high confinement DIII-D plasmas' (Nucl. Fusion 45 595-607). The awards were presented by the IAEA Deputy Director General, Werner Burkart, and the Chairman of the Board of Editors, Mitsuru Kikuchi, on 16 October 2008 at the 22nd IAEA Fusion Energy Conference in Geneva, Switzerland. Given the topicality of these papers for the ITER design, it is a matter of pride to the journal that the work should be published in Nuclear Fusion. Reviews Like many who have worked for a long time in the field, I still make use of Nuclear Fusion Reviews that go back 20 or 30 years. It is particularly useful, therefore, that the Board of Editors has been working to re-activate the review programme. The first fruits will appear in this issue, in the form of `A review of zonal flow experiments', by Akihide Fujisawa. The special procedures for Reviews should be noted: most specifically that they should normally be commissioned by the Board of Editors. However, not only is the Board of Editors working on a programme but I am sure that they would be pleased to consider suggestions for review subjects. Letters The reputation of Nuclear

  6. Linguistic Prescriptivism in Letters to the Editor

    ERIC Educational Resources Information Center

    Lukac, Morana

    2016-01-01

    The public's concern with the fate of the standard language has been well documented in the history of the complaint tradition. The print media have for centuries featured letters to the editor on questions of language use. This study examines a corpus of 258 language-related letters to the editor published in the English-speaking print media. By…

  7. Editorial Commentary: Editor's Conflict of Interest.

    PubMed

    Lubowitz, James H

    2015-09-01

    The Editor-in-chief has recused himself from industry consulting, which he performed before assuming the position, and returned related royalties and divested related stock options, in order to mitigate against conflict-of-interest. The Editor discloses affiliation with an institution that receives support from diverse industry partners in support of research and education.

  8. Linguistic Prescriptivism in Letters to the Editor

    ERIC Educational Resources Information Center

    Lukac, Morana

    2016-01-01

    The public's concern with the fate of the standard language has been well documented in the history of the complaint tradition. The print media have for centuries featured letters to the editor on questions of language use. This study examines a corpus of 258 language-related letters to the editor published in the English-speaking print media. By…

  9. An Idea Book for the Education Editor.

    ERIC Educational Resources Information Center

    Brodinsky, Ben, Ed.

    To be used as a reference and guide for education editors, this booklet contains advice and information on writing, editing, production, publishing, the magazine, and the newsletter. The final section discusses the role and duties of the education editor. This edition contains material from the 1963 brochure of the same name, new material selected…

  10. LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty.

    PubMed

    Tommiska, Johanna; Sørensen, Kaspar; Aksglaede, Lise; Koivu, Rosanna; Puhakka, Lea; Juul, Anders; Raivio, Taneli

    2011-09-22

    Pubertal timing is a strongly heritable trait, but no single puberty gene has been identified. Thus, the genetic background of idiopathic central precocious puberty (ICPP) is poorly understood. Overall, the genetic modulation of pubertal onset most likely arises from the additive effect of multiple genes, but also monogenic causes of ICPP probably exist, as cases of familial ICPP have been reported. Mutations in KISS1 and KISSR, coding for kisspeptin and its receptor, involved in GnRH secretion and puberty onset, have been suggested causative for monogenic ICPP. Variation in LIN28B was associated with timing of puberty in genome-wide association (GWA) studies. LIN28B is a human ortholog of the gene that controls, through microRNAs, developmental timing in C. elegans. In addition, Lin28a transgenic mice manifest the puberty phenotypes identified in the human GWAS. Thus, both LIN28B and LIN28A may have a role in pubertal development and are good candidate genes for monogenic ICPP. Thirty girls with ICPP were included in the study. ICPP was defined by pubertal onset before 8 yrs of age, and a pubertal LH response to GnRH testing. The coding regions of LIN28B, LIN28A, KISS1, and KISS1R were sequenced. The missense change in LIN28B was also screened in 132 control subjects. No rare variants were detected in KISS1 or KISS1R in the 30 subjects with ICPP. In LIN28B, one missense change, His199Arg, was found in one subject with ICPP. However, this variant was also detected in one of the 132 controls. No variation in LIN28A was found. We did not find any evidence that mutations in LIN28B or LIN28A would underlie ICPP. In addition, we confirmed that mutations in KISS1 and KISS1R are not a common cause for ICPP.

  11. Lin28 enhances tissue repair by reprogramming cellular metabolism.

    PubMed

    Shyh-Chang, Ng; Zhu, Hao; Yvanka de Soysa, T; Shinoda, Gen; Seligson, Marc T; Tsanov, Kaloyan M; Nguyen, Liem; Asara, John M; Cantley, Lewis C; Daley, George Q

    2013-11-07

    Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly conserved RNA-binding protein expressed during embryogenesis, plays roles in development, pluripotency, and metabolism. To determine whether Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles and accelerated regrowth of cartilage, bone, and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however, let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PAPERCLIP: Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Lin28 enhances tissue repair by reprogramming cellular metabolism

    PubMed Central

    Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Nguyen, Liem; Asara, John M.; Cantley, Lewis C.; Daley, George Q.

    2014-01-01

    SUMMARY Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly-conserved RNA binding protein expressed during embryogenesis, plays roles in development, pluripotency and metabolism. To determine if Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles, and accelerated regrowth of cartilage, bone and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically-induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PMID:24209617

  13. Lin28a regulates germ cell pool size and fertility.

    PubMed

    Shinoda, Gen; De Soysa, T Yvanka; Seligson, Marc T; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P; Gregory, Richard I; Moss, Eric G; Daley, George Q

    2013-05-01

    Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males, the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild-type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. Copyright © 2013 AlphaMed Press.

  14. LIN28 expression in rat spinal cord after injury.

    PubMed

    Yue, Ying; Zhang, Dongmei; Jiang, Shengyang; Li, Aihong; Guo, Aisong; Wu, Xinming; Xia, Xiaopeng; Cheng, Hongbing; Tao, Tao; Gu, Xingxing

    2014-05-01

    LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. However, its expression and function in central nervous system still unclear. In this study, we performed an acute spinal cord contusion injury (SCI) model in adult rats and investigated the dynamic changes of LIN28 expression in spinal cord. Western blot and immunohistochemistry analysis revealed that LIN28 was present in normal spinal cord. It gradually increased, reached a peak at 3 day, and then nearly declined to the basal level at 14 days after SCI. Double immunofluorescence staining showed that LIN28 immunoreactivity was found in neurons, astrocytes and a handful of microglia. Interestingly, LIN28 expression was increased predominantly in astrocytes but not in neurons. Moreover, the colocalization of LIN28 and proliferating cell nuclear antigen was detected after injury. Western blot showed that LIN28 participated in lipopolysaccharide (LPS) induced astrocytes inflammatory responses by NF-κB signaling pathway. These results suggested that LIN28 may be involved in the pathologic process of SCI, and further research is needed to have a good understanding of its function and mechanism.

  15. Lin Piao and the Doctrine of Confucius and Mencius

    ERIC Educational Resources Information Center

    Chinese Education, 1974

    1974-01-01

    This article examines how Lin Piao used the teaching and ideology of Confucius and Mencius as the backbone of his attempted coup d'etat in 1970. The elitist nature of Confucian philosophy, and Lin Piao's attempt to use Confucius to reject historical materialism is emphasized. (DE)

  16. LIN28B Promotes Colon Cancer Migration and Recurrence

    PubMed Central

    Pang, Minghui; Wu, Gang; Hou, Xiaolin; Hou, Nengyi; Liang, Liqin; Jia, Guiqing; Shuai, Ping; Luo, Bin; Wang, Kang; Li, Guoxin

    2014-01-01

    LIN28B is involved in “stemness” and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer. PMID:25360631

  17. [2009 report from the editors].

    PubMed

    García Puig, J; Gaspar Alonso-Vega, G; Ríos Blanco, J J

    2010-01-01

    The editors of the Rev Clin Esp present the editorial course of action of the journal over the past year. We have up-dated the design of the journal, its contents (sections) and computerized the editorial process. We processed 467 manuscripts and made an editorial decision on 402 of them between November 2008 and October 2009. A total of 92 manuscripts (23%) were accepted. Fifteen (13%) out of the 119 original articles for which the editorial process was completed were accepted. Our goal for the year 2010 is to make the journal available on the Internet for all those who are subscribers to the Rev Clin Esp as well as for internal medicine residents (for which they must be members of each regional society). Other objectives of the editorial team are to edit the E-cases, for the journal to be a continuing education tool and that the coordinators of the work groups develop a monographic number at least once every two years. These actions aim to increase the impact factor and the quality of the Rev Clin Esp, official publication of the Spanish Society of Internal Medicine and of Spanish-speaking internal medicine physicians.

  18. EDITORIAL: Letter from the Editor Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Pashinin, Pavel P.

    2013-01-01

    Dear readers, contributors, and members of the world laser physics community. It is a great honour for us to introduce to you our new publishing partner, IOP Publishing, a subsidiary of the Institute of Physics, United Kingdom. IOP Publishing is a world renowned authority in producing journals, magazines, websites and services that enable researchers and research organizations to present their work to a world-wide audience. Laser Physics, the first English-language scientific journal in Russia, was founded in 1990 on the initiative of Alexander M Prokhorov, a pioneer and leader in laser physics research. Professor Prokhorov served as the first Editor-in-Chief of the journal until 2002. We are proud that it is our 23rd year of publishing Laser Physics and our 10th year of publishing Laser Physics Letters. We would like to honour the memory of our friend, late Professor Igor Yevseyev, whose enthusiasm and unwavering dedication to our journals contributed most significantly to their success. It was initially his idea in 2011 to approach IOP with a partnership proposal. We deeply regret that he is no longer with us as we enter this productive alliance. Now, in partnership with IOP, we are turning a new page in providing world-wide access to the cutting-edge research results in our journals, serving our well established global audience. We see new horizons opening for our journals for years to come and hope that our readers share our enthusiasm and aspirations. Please accept our best wishes for all your new scientific endeavors in the exciting field of laser physics.

  19. Sir William Wilde: an enlightened editor.

    PubMed

    O'Doherty, M

    2016-05-01

    This paper examines Sir William Wilde's peculiar genius as editor, his contribution to the Irish Journal of Medical Science in ensuring its endurance and making it a treasure-house of the history of medicine in Ireland.

  20. Richard Gilbert, Reporter and Assistant City Editor.

    ERIC Educational Resources Information Center

    Bender, Larry

    1988-01-01

    Looks at the experiences of Richard Gilbert, reporter and assistant editor for "The Herald Telephone," a daily newspaper in Bloomington, Indiana, and discusses Gilbert's suggested guidelines for high school journalism advisers. (MS)

  1. Ethical issues faced by nursing editors.

    PubMed

    Freda, Margaret Comerford; Kearney, Margaret H

    2005-06-01

    This study reports on ethical issues faced by editors of nursing journals, a topic which has not appeared in the nursing literature. A survey of nursing editors (n = 88)was conducted via e-mail; this article is the content analysis of survey questions about ethics. Eight categories of ethical issues emerged: problems with society/association/publisher; decisions about inflammatory submissions; informed consent or IRB issues; conflicts of interest; advertising pressures; duplicate publications and/or plagiarism; difficult interactions with authors; and authorship. Some issues were similar to those published about medical editors; however, others were unique. This study can assist authors to better understand some of the ethical issues in publishing, can help editors to view their issues in the context of what others experience, and can assist societies and publishers to work toward avoiding these ethical issues in the future. Professional discussions about ethics in nursing publications should be the subject of ongoing research and scientific inquiry.

  2. Headline Ideas from Reporters Help Copy Editors.

    ERIC Educational Resources Information Center

    Haber, Marian Wynne

    1984-01-01

    Presents a method that has student reporters write headline suggestions on their stories before submission to avoid nonsignificant headlines. This technique was judged worthwhile by three professional copy editors. (CRH)

  3. Report of the editors, 2014.

    PubMed

    García Puig, J; Gaspar Alonso-Vega, G; Ríos Blanco, J J

    2015-01-01

    The editors of Revista Clínica Española(Rev Clin Esp) inform on their editorial activity during the last 12 months: (a) Objectives and attainments in 2014, (b) Editorial activity, 2014, and (c) 2013 impact factor. In 2014 we achieved the 5 planned objectives. We have published the 9 programmed issues and 103% of the planned papers according to the usual fixed sections. We emphasize the publication of 29 editorials, 21 of which are signed by prestigious foreign authors. From the first January to the 30th September 2014 we received 421 manuscripts (46.8 manuscripts per month), a slight lower figure to that obtained in 2013 (50.9 manuscripts per month). The acceptance rate of the 404 manuscripts whose editorial process has been concluded was 32.3% (originals, 22.4%). We asked for 315 revisions to 240 reviewers and we received 53.3% revisions in less than two weeks (10.4 days). The mean time to adopt an editorial decision for all manuscripts («accepted»/«rejected») has been 18,3 (less than half than in 2009). For «originals» this figure has dropped from 56,6 days in 2009 to 26.6 days in 2014. The mean time elapsed from manuscript reception to its on-line publication was 103 days. In 2014 the collaboration with the working groups from the Internal Medicine Spanish Foundation (FEMI) has reported 11 published manuscripts. In July 2014 we were informed that the Journal Citation Reports gave Rev Clin Esp an Impact Factor of 1,314 (year 2013). This Impact Factor without self-citations would have been 0.705 (in 2009 the global impact factor was 0,584). With the Editorial Committee farewell we welcome the new editorial team and we sincerely thank the SEMI Steering Committee, our colleagues, journal officers, reviewers, readers and authors that since 2009 have trusted on our editorial work.

  4. [Report of the editors, 2010].

    PubMed

    García Puig, Juan; Alonso-Vega, Gabriel Gaspar; Blanco, Juan José Ríos

    2011-01-01

    The Editors of the Rev Clin Esp inform herein on their editorial activity in the last year (November 2009 to October 2010) according to three different sections: (a) Objectives and achievements during 2010, (b) editorial activity, and (c) objectives for 2011. During 2010, we have updated the editorial algorithm (manuscript time lag). We have developed the "E-case reports" section and we have linked the abstracts of the Annual Congress of the Spanish Society of Internal Medicine (SEMI) to a journal supplement (electronically available). Since 2010, the subscribers have been able to receive all of the contents of the Rev Clin Esp on-line and to perform self-evaluations in order to obtain 1.7 credits per each journal issue (continuing education). In 2010 we handled 402 manuscripts (7.2% more than in 2009), 35% of which were accepted for publication. We asked 186 reviewers for their expert opinion, 75% of whom sent their reports in less than two weeks. The mean time needed to reach an editorial decision concerning original manuscripts ("accepted / rejected") was 44.5 days and for papers not sent to external reviewers 19.5 days. Collaboration with the work groups produced good results (2.4 published manuscripts per issue), but this could be improved if all the groups collaborated in all the journal sections. Our objectives for 2011 are to complete the renewal of the Rev Clin Esp scientific committee, in accordance with the SEMI Council, and to continue to proceed with the actions initiated to increase the journal impact factor. Rev Clim Esp is an open forum for all internal medicine specialists. Responsibility falls on all of us to collaborate in order to make our journal a little better day by day.

  5. 2012 Editors' Citations for Excellence in Refereeing

    NASA Astrophysics Data System (ADS)

    2013-09-01

    One of the most important services performed for AGU is the conscientious reviewing of submitted papers. Because of the nature of the reviewing process, this service is also one of the least recognized. Every year editors are asked to select the outstanding reviewers from the previous year. The reviewers listed below have been cited by editors of AGU journals and Eos for excellence in refereeing. These individuals are to be commended for consistently providing constructive and thoughtful reviews.

  6. 2013 Editors' Citations for Excellence in Refereeing

    NASA Astrophysics Data System (ADS)

    2014-06-01

    One of the most important services performed for AGU is the conscientious reviewing of submitted papers. Because of the nature of the reviewing process, this service is also one of the least recognized. Every year editors are asked to select the outstanding reviewers from the previous year. The reviewers listed below have been cited by editors of AGU journals and Eos for excellence in refereeing. These individuals are to be commended for consistently providing constructive and thoughtful reviews.

  7. DeviceEditor visual biological CAD canvas

    PubMed Central

    2012-01-01

    Background Biological Computer Aided Design (bioCAD) assists the de novo design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly. Results We report the development and deployment of web-based bioCAD software, DeviceEditor, which provides a graphical design environment that mimics the intuitive visual whiteboard design process practiced in biological laboratories. The key innovations of DeviceEditor include visual combinatorial library design, direct integration with scar-less multi-part DNA assembly design automation, and a graphical user interface for the creation and modification of design specification rules. We demonstrate how biological designs are rendered on the DeviceEditor canvas, and we present effective visualizations of genetic component ordering and combinatorial variations within complex designs. Conclusions DeviceEditor liberates researchers from DNA base-pair manipulation, and enables users to create successful prototypes using standardized, functional, and visual abstractions. Open and documented software interfaces support further integration of DeviceEditor with other bioCAD tools and software platforms. DeviceEditor saves researcher time and institutional resources through correct-by-construction design, the automation of tedious tasks, design reuse, and the minimization of DNA assembly costs. PMID:22373390

  8. How are Editors Selected, Recruited and Approved?

    PubMed

    Teixeira da Silva, Jaime A; Al-Khatib, Aceil

    2016-11-28

    The editors of scholarly journals have a duty to uphold and promote the highest standards of ethical conduct of research. They also have a responsibility to maintain the integrity of the literature, and to promote transparency and honesty in reporting research findings. In the process of screening manuscripts they receive for possible publication, editors have the obligation to report infractions to the institutions of offending authors, and request an investigation. Since editors can reject a paper on ethical grounds, they can be considered to be the guardians of ethics who should express high ethical standards in conducting and publishing their own research. An examination of several publishers' websites reveals no such requirement or clear selection criteria for journal editors. Therefore, we aim to discuss the factors that publishers, in a broad sense, should consider when selecting editors for scholarly journals and believe that such criteria should be made public to ensure accountability. This would restore some of the eroding public trust in disseminated research, fortify confidence in the composition and qualification of members of an editorial board, and help to protect the reputations of publishers and editors.

  9. The Lin28/let-7 axis regulates glucose metabolism

    PubMed Central

    Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

    2012-01-01

    SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

  10. DNA methylation of the LIN28 pseudogene family.

    PubMed

    Davis, Aaron P; Benninghoff, Abby D; Thomas, Aaron J; Sessions, Benjamin R; White, Kenneth L

    2015-04-11

    DNA methylation directs the epigenetic silencing of selected regions of DNA, including the regulation of pseudogenes, and is widespread throughout the genome. Pseudogenes are decayed copies of duplicated genes that have spread throughout the genome by transposition. Pseudogenes are transcriptionally silenced by DNA methylation, but little is known about how pseudogenes are targeted for methylation or how methylation levels are maintained in different tissues. We employed bisulfite next generation sequencing to examine the methylation status of the LIN28 gene and four processed pseudogenes derived from LIN28. The objective was to determine whether LIN28 pseudogenes maintain the same pattern of methylation as the parental gene or acquire a methylation pattern independent of the gene of origin. In this study, we determined that the methylation status of LIN28 pseudogenes does not resemble the pattern evident for the LIN28 gene, but rather these pseudogenes appear to acquire methylation patterns independent of the parental gene. Furthermore, we observed that methylation levels of the examined pseudogenes correlate to the location of insertion within the genome. LIN28 pseudogenes inserted into gene bodies were highly methylated in all tissues examined. In contrast, pseudogenes inserted into genomic regions that are not proximal to genes were differentially methylated in various tissue types. Our analysis suggests that Lin28 pseudogenes do not acquire patterns of tissue-specific methylation as for the parental gene, but rather are methylated in patterns specific to the local genomic environment into which they were inserted.

  11. The Lin28/let-7 axis regulates glucose metabolism.

    PubMed

    Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V; Shinoda, Gen; Shah, Samar P; Einhorn, William S; Takeuchi, Ayumu; Engreitz, Jesse M; Hagan, John P; Kharas, Michael G; Urbach, Achia; Thornton, James E; Triboulet, Robinson; Gregory, Richard I; Altshuler, David; Daley, George Q

    2011-09-30

    The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. RNA-binding protein Lin28 in cancer and immunity.

    PubMed

    Jiang, Shuai; Baltimore, David

    2016-05-28

    The highly conserved RNA-binding protein, Lin28, is involved in many biological processes, including development, reprogramming, pluripotency, and metabolism. Importantly, Lin28 functions as an oncogene, promoting tumor progression and metastasis in various human cancers. Lin28 can regulate gene expression either by directly binding to mRNAs or by blocking microRNA biogenesis, and the underlying mechanisms include Let-7-dependent and Let-7-independent modes of action. Recent evidence shows that Lin28 also plays a fundamental role in immunity. The roles of Lin28 in disease are complex and require characterization of its physiological functions in cancer and immunological contexts. Here we review emerging information on the role of Lin28 in cancer and immunity and the molecular mechanisms it uses. We discuss our present knowledge of the system and highlight remaining mysteries related to the functions of this small RNA-binding protein. This knowledge may lead to Lin28 becoming a diagnostic marker for cancer or immune-related diseases and a possible therapeutic target.

  13. EDITORIAL: Message from the Editor Message from the Editor

    NASA Astrophysics Data System (ADS)

    Thomas, Paul

    2012-01-01

    Board Members, Guest Editors of special editions and those referees who were already listed in the last years. The following people have been selected: Marina Becoulet, CEA Cadarache, France Russell Doerner, University of California - San Diego, USA Emiliano Fable, Max-Planck-Institut fuer Plasmaphysik, Germany Akihide Fujisawa, Kyushi University, Japan Gerardo Giruzzi, CEA Cadarache, France Grigory Kagan, LANL, USA Morten Lennholm, CCFE, UK Akinobu Matsuyama, NIFS, Japan Peter Stangeby, University of Toronto, Canada Leonid Zakharov, PPPL, USA In addition, there is a group of several hundred referees who have helped us in the past year to maintain the high scientific standard of Nuclear Fusion. At the end of this issue we give the full list of all referees for 2011. Our thanks to them! Authors The winner of the 2011 Nuclear Fusion Award is H. Urano, for the paper 'Dimensionless parameter dependence of H-mode pedestal width using hydrogen and deuterium plasmas in JT-60U' (Nucl. Fusion 48 045008). The award was presented at the Plasma Conference 2011 (Joint meeting of 28th JSPF Annual Meeting, The 29th Symposium on Plasma Processing, and Division of Plasma Physics, 2011 Autumn Meeting of The Physical Society of Japan). This is the sixth year that the International Atomic Energy Agency (IAEA) has awarded an annual prize to honour exceptional work published in Nuclear Fusion. IOP Publishing has generously made a contribution of $2500 to the award. The Nuclear Fusion Electronic Archive The journal's electronic archive has been online since the beginning of the year. The archive has been a roaring success and has contributed to the nearly 300 000 downloads of journal papers in 2011. The archive can be accessed via http://iopscience.iop.org/0029-5515/page/Archive. It has direct links to 16 landmark papers, from authors such as Artsimovich and Mercier. The Nuclear Fusion office and IOP Publishing Just as the journal depends on the authors and referees, so its success is also

  14. A Small-Molecule Inhibitor of Lin28.

    PubMed

    Roos, Martina; Pradère, Ugo; Ngondo, Richard P; Behera, Alok; Allegrini, Sara; Civenni, Gianluca; Zagalak, Julian A; Marchand, Jean-Rémy; Menzi, Mirjam; Towbin, Harry; Scheuermann, Jörg; Neri, Dario; Caflisch, Amedeo; Catapano, Carlo V; Ciaudo, Constance; Hall, Jonathan

    2016-10-21

    New discoveries in RNA biology underscore a need for chemical tools to clarify their roles in pathophysiological mechanisms. In certain cancers, synthesis of the let-7 microRNA tumor suppressor is blocked by an RNA binding protein (RBP) Lin28, which docks onto a conserved sequence in let-7 precursor RNA molecules and prevents their maturation. Thus, the Lin28/let-7 interaction might be an attractive drug target, if not for the well-known difficulty in targeting RNA-protein interactions with drugs. Here, we describe a protein/RNA FRET assay using a GFP-Lin28 donor and a black-hole quencher (BHQ)-labeled let-7 acceptor, a fluorescent protein/quencher combination which is rarely used in screening despite favorable spectral properties. We tested 16 000 molecules and identified N-methyl-N-[3-(3-methyl[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl]acetamide, which blocked the Lin28/let-7 interaction, rescued let-7 processing and function in Lin28-expressing cancer cells, induced differentiation of mouse embryonic stem cells, and reduced tumor-sphere formation by 22Rv1 and Huh7 cells. A biotinylated derivative captured Lin28 from cell lysates consistent with an on-target mechanism in cells, though the compound also showed some activity against bromodomains in selectivity assays. The Lin28/let-7 axis is presently of high interest not only for its role as a bistable switch in stem-cell biology but also because of its prominent roles in numerous diseases. We anticipate that much can be learned from the use of this first reported small molecule antagonist of Lin28, including the potential of the Lin28/let-7 interaction as a new drug target for selected cancers. Furthermore, this approach to assay development may be used to identify antagonists of other RBP/RNA interactions suspected to be operative in pathophysiological mechanisms.

  15. On the low regularity of the Benney-Lin equation

    NASA Astrophysics Data System (ADS)

    Chen, Wengu; Li, Junfeng

    2008-03-01

    We consider the low regularity of the Benney-Lin equation ut+uux+uxxx+[beta](uxx+uxxxx)+[eta]uxxxxx=0. We established the global well posedness for the initial value problem of Benney-Lin equation in the Sobolev spaces for 0[greater-or-equal, slanted]s>-2, improving the well-posedness result of Biagioni and Linares [H.A. Biaginoi, F. Linares, On the Benney-Lin and Kawahara equation, J. Math. Anal. Appl. 211 (1997) 131-152]. For s<-2 we also prove some ill-posedness issues.

  16. [Report of the editors, 2013].

    PubMed

    García Puig, J; Gaspar Alonso-Vega, G; Ríos Blanco, J J

    2014-01-01

    The editors of Revista Clínica Española(Rev Clin Esp) inform on their editorial activity during the last 12 months: (a) objectives and attainments, (b) editorial activity, and (c) objectives for 2014. In 2013 the most relevant modification concerning the editorial activity has been the translation into English of the 5 manuscripts with abstract contained in each issue (http://www.revclinesp.es/). From the first January to the 30th September 2013 we received 458 manuscripts (50.9 manuscripts per month), a similar figure to that obtained in 2012 (51.1 manuscripts per month). The acceptance rate of the 443 manuscripts whose editorial process has been concluded was 23.7% (originals, 11.8%). We asked for 253 revisions to 186 reviewers and we received 74.4% revisions in less than 2 weeks (10.9 days). The mean time to adopt an editorial decision for all manuscripts («accepted»/«rejected») has been 20,3 (half than in 2009). For «originals» this figure has dropped from 56.6 days in 2009 to 22.5 days in 2013. The mean time elapsed from manuscript reception to its on-line publication was 94.8 days in 2013 (110.5 in 2012 and 155.8 in 2011). In 2013 the collaboration with the working groups from the Internal Medicine Spanish Foundation has reported 17 published manuscripts. In 2013 we were informed that the Journal Citation Reports excluded Rev Clin Esp from its impact factor journal list due to its elevated self-citations. We have taken a number of actions to reduce self-citations and we expect to be a minority in 2014. Some other data concerning the editorial policy are encouraging. In this sense, manuscript citation to Rev Clin Esp published articles has seen a substantial increase from 19% in 2008 to 29% in 2012. We work to achieve the digitalization of Rev Clin Esp from 1940 to 1999 (the journal is already digitalized since 2000). The continuous renewal of the journal sections and the working groups collaboration are necessary elements to make our journal, each day

  17. EDITORIAL: Letter from the Editor Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Hauptmann, Peter

    2011-01-01

    Dear authors and reviewers of articles for Measurement Science and Technology, I would like to thank all those who have published papers with us in 2010, and special thanks go to those of you who have kindly reviewed articles for the journal. I would also like to take this opportunity to update you on some of the developments on the journal and look ahead to 2011. As many of you are no doubt aware, our impact factor (a measure of the average number of times recent papers are referred to by others) is currently 1.317. This is often taken as an indication of the quality and relevance of recently published research, and although as readers we develop our own instinct for journals of high quality, it is gratifying as an Editor to see the data from an independent organization (Thomson ISI) agreeing with my own assessment. Measurement Science and Technology is a journal with a broad scope covering new measurement techniques in all fields of science and engineering. I therefore find it particularly enjoyable to read summaries of recent research in our strong topical review programme as these cover many varied topics of interest. In 2010 several interesting articles by international leaders in their field were published, for example: Single-photon generation and detection, by G S Buller and R J Collins of Heriot-Watt University [1]. Fluorescence lifetime imaging microscopy in life sciences, by Jan Willem Borst and Antonie J W G Visser, from the Microspectroscopy Centre of Wageningen University [2]. Biological and chemical sensors for cancer diagnosis, by Elfriede Simon of Siemens AG [3]. I hope that these articles, and the others published in 2010 and now in 2011, will provide a useful overview for our readers, and be helpful to new researchers. When speaking to young researchers I am particularly aware that having their articles published in a timely fashion is important, and I am pleased that our publication times are highly competitive, with most authors receiving a

  18. [The Chilean Association of Biomedical Journal Editors].

    PubMed

    Reyes, H

    2001-01-01

    On September 29th, 2000, The Chilean Association of Biomedical Journal Editors was founded, sponsored by the "Comisión Nacional de Investigación Científica y Tecnológica (CONICYT)" (the Governmental Agency promoting and funding scientific research and technological development in Chile) and the "Sociedad Médica de Santiago" (Chilean Society of Internal Medicine). The Association adopted the goals of the World Association of Medical Editors (WAME) and therefore it will foster "cooperation and communication among Editors of Chilean biomedical journals; to improve editorial standards, to promote professionalism in medical editing through education, self-criticism and self-regulation; and to encourage research on the principles and practice of medical editing". Twenty nine journals covering a closely similar number of different biomedical sciences, medical specialties, veterinary, dentistry and nursing, became Founding Members of the Association. A Governing Board was elected: President: Humberto Reyes, M.D. (Editor, Revista Médica de Chile); Vice-President: Mariano del Sol, M.D. (Editor, Revista Chilena de Anatomía); Secretary: Anna María Prat (CONICYT); Councilors: Manuel Krauskopff, Ph.D. (Editor, Biological Research) and Maritza Rahal, M.D. (Editor, Revista de Otorrinolaringología y Cirugía de Cabeza y Cuello). The Association will organize a Symposium on Biomedical Journal Editing and will spread information stimulating Chilean biomedical journals to become indexed in international databases and in SciELO-Chile, the main Chilean scientific website (www.scielo.cl).

  19. A standard syntax-directed editor for hyperprogramming systems

    SciTech Connect

    Zhogolev, E.A.; Kuz`menkova, E.A.; Mailingova, O.L.; Poprygaev, E.V.

    1995-05-01

    The main operations of a syntax-directed editor are considered. The requirements to the standard syntax-directed editor are stated. The structure of the standard syntax-directed editor and the functions of its components are discussed. The language base properties needed for syntax-directed editor development are described. Methods for transforming the standard syntax-directed editor into a specialized one are carried out.

  20. AGU Publications Volunteers Feted At Elegant Editors' Evening

    NASA Astrophysics Data System (ADS)

    Panning, Jeanette

    2013-01-01

    The 2012 Fall Meeting Editors' Evening, held at the City Club of San Francisco, was hosted by the Publications Committee and is the premier social event for editors and associate editors attending the Fall Meeting. The evening commenced with a welcome from Carol Finn, incoming AGU president, in which she expressed her thanks to the editors and associate editors for volunteering their time to benefit AGU.

  1. In vitro expansion of Lin{sup +} and Lin{sup −} mononuclear cells from human peripheral blood

    SciTech Connect

    Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul; Rohaya, M. A. W.

    2013-11-27

    Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin{sup −}) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin{sup +}) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin{sup −} cell population. The ability of Lin{sup +} and Lin{sup −} to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin{sup +} and Lin{sup −} were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin{sup +} mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin{sup −} stem cells were not able to survive in proliferation medium however

  2. lin-8, which antagonizes Caenorhabditis elegans Ras-mediated vulval induction, encodes a novel nuclear protein that interacts with the LIN-35 Rb protein.

    PubMed

    Davison, Ewa M; Harrison, Melissa M; Walhout, Albertha J M; Vidal, Marc; Horvitz, H Robert

    2005-11-01

    Ras-mediated vulval development in C. elegans is inhibited by the functionally redundant sets of class A, B, and C synthetic Multivulva (synMuv) genes. Three of the class B synMuv genes encode an Rb/DP/E2F complex that, by analogy with its mammalian and Drosophila counterparts, has been proposed to silence genes required for vulval specification through chromatin modification and remodeling. Two class A synMuv genes, lin-15A and lin-56, encode novel nuclear proteins that appear to function as a complex. We show that a third class A synMuv gene, lin-8, is the defining member of a novel C. elegans gene family. The LIN-8 protein is nuclear and can interact physically with the product of the class B synMuv gene lin-35, the C. elegans homolog of mammalian Rb. LIN-8 likely acts with the synMuv A proteins LIN-15A and LIN-56 in the nucleus, possibly in a protein complex with the synMuv B protein LIN-35 Rb. Other LIN-8 family members may function in similar complexes in different cells or at different stages. The nuclear localization of LIN-15A, LIN-56, and LIN-8, as well as our observation of a direct physical interaction between class A and class B synMuv proteins, supports the hypothesis that the class A synMuv genes control vulval induction through the transcriptional regulation of gene expression.

  3. How does Lin28 let-7 control development and disease?

    PubMed Central

    Thornton, James E.; Gregory, Richard I.

    2012-01-01

    One of the most ancient and highly conserved microRNAs (miRNAs), the let-7 family, has gained notoriety owing to its regulation of stem cell differentiation, essential role in normal development, as well as its tumor suppressor function. Mechanisms controlling let-7 expression have recently been uncovered, specifically the role of the RNA-binding protein Lin28 – a key developmental regulator - in blocking let-7 biogenesis. This review focuses on our current understanding of the Lin28-mediated control of let-7 maturation and highlights the central role of Lin28 in stem cell biology, development, control of glucose metabolism, and dysregulation in human disease. Manipulating the Lin28 pathway for the precise control of let-7 expression may therefore provide novel therapeutic opportunities for cancer and other diseases. PMID:22784697

  4. EDITORIAL: Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Hauptmann, Peter

    2009-01-01

    Marella de Angelis and her colleagues on precision gravimetry using atomic sensors and from Dr Peter Becker on determination of the Avogadro constant via enriched silicon-28. I recommend setting up a free e-mail alert so that you can read them as soon as they are published! As many of you are already aware, our impact factor (a measure of the average number of times recent papers are referred to by others) has risen again to 1.297. This is often taken as an indication of the quality and relevance of recently published research, and although as readers we develop our own instinct for journals of high quality, it is gratifying as an Editor to see the data from an independent organization (Thomson ISI) agreeing with my own assessment. Of course the publication of high quality articles in the journal is dependent both on you the authors who trust us with the publication of your best work and on our referees and Editorial Board Members who we depend on to maintain the high standards you have grown to expect. I must also thank our referees for their rapid response when asked to review papers for Measurement Science and Technology. On average, authors receive a decision on their article in 45 days. Therefore I would like to end this message by saying thank you again to all those who have contributed to our success in the past year, and wish you all the best for a successful 2009!

  5. EDITORIAL: Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Hauptmann, Peter

    2008-01-01

    Dear authors and reviewers of articles for Measurement Science and Technology, I would like to thank all those who have published papers with us in 2007, and special thanks go to those of you who have kindly reviewed articles for the journal this year. I would also like to take this opportunity to update you on some of the developments on the journal. As many of you are no doubt aware, our latest impact factor (a measure of the average number of times recent papers are referred to by others) has risen to 1.228. This is often taken as an indication of the quality and relevance of recently published research, and although as readers we develop our own instinct for journals of high quality, it is gratifying as an Editor to see the data from an independent organization agreeing with my own assessment. The popularity of the journal amongst authors and readers has prompted us to introduce a new subject classification for articles, to make it easier for readers to find articles of interest. The eight subject categories are: Measurement theory and practical developments (e.g. precision measurements, metrology, new measurement principles, signal processing techniques, theory of measurement, calibration); Sensors and sensing systems (based on physical, chemical or biological principles; micro- and nano-scale systems; sensors for physical, chemical and biological quantities); Optical and laser based techniques (e.g. fibre optics, interferometry, etc); Fluid mechanics measurements (e.g. fluid flow, velocimetry, particle sizing, etc); Imaging techniques (e.g. tomography, microscopy, holography, THz, etc); Spectroscopy (e.g. optical, acoustic, dielectric, MS, NMR, ESR, IR, UV-VIS, fluorescence, PCS, x-ray, etc); New and improved techniques for materials evaluation (e.g. non-destructive testing and evaluation, structural measurements); Novel instrumentation. We kindly ask you to assign your paper to a category when you send it to the journal. In order to maintain our rapid

  6. EDITORIAL: Message from the Editor

    NASA Astrophysics Data System (ADS)

    Thomas, Paul

    2008-01-01

    To begin, I would like to wish our readers, authors, referees and Board of Editors a successful and happy 2008 and thank them for their contributions to Nuclear Fusion in 2007. I took over the editorship of Nuclear Fusion in January, and the year has been one in which the community as a whole has been busier than ever with a variety of duties associated with the ITER project. It was with pride that we published the Progress in the ITER Physics Basis in the June issue of the journal (stacks.iop.org/NF/47/i=6). The task undertaken by the coordinators, authors and referees was a daunting one but one which led to an outstandingly successful issue. The response from readers has been phenomenal and there were in the region of 10 000 downloads of papers in the first month following publication. Looking to 2008 and beyond, the journal will endeavour to continue to support the work of the fusion community. Refereeing As we have done since January 2005, we would like to thank our top ten most loyal referees who have helped the journal with its double-referee peer-review procedure in the past year. At the Nuclear Fusion Editorial Office we are fully aware of the load we put on the shoulders of our referees. At the end of 2004 the Editorial Board decided that a gesture of gratitude should be made to our most loyal referees. We offer them a personal subscription to Nuclear Fusion with electronic access for one year, free of charge. To select the top referees we have adopted the criterion that a researcher should have acted as a referee or adjudicator for at least three different manuscripts during the period from summer 2006 to the end of 2007. We have excluded our Board members and those referees who were already listed in the top ten in the last two years. According to our records the following people met this criterion. Congratulations and many, many thanks! H.L. Berk (Texas University, USA) J.S. DeGrassie (GAT, USA) C. Deutsch (Paris University, France) N. Hayashi (JAEA

  7. The LIN28/let-7 Pathway in Cancer.

    PubMed

    Balzeau, Julien; Menezes, Miriam R; Cao, Siyu; Hagan, John P

    2017-01-01

    Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function. For LIN28B, the precise mechanism responsible for let-7 inhibition remains controversial. Functionally, the decrease in let-7 microRNAs leads to overexpression of their oncogenic targets such as MYC, RAS, HMGA2, BLIMP1, among others. Furthermore, mouse models demonstrate that ectopic LIN28 expression is sufficient to drive and/or accelerate tumorigenesis via a let-7 dependent mechanism. In this review, the LIN28/let-7 pathway is discussed, emphasizing its role in tumorigenesis, cancer stem cell biology, metabolomics, metastasis, and resistance to ionizing radiation and several chemotherapies. Also, emerging evidence will be presented suggesting that molecular targeting of this pathway may provide therapeutic benefit in cancer.

  8. LIN28A Expression Reduces Sickling of Cultured Human Erythrocytes

    PubMed Central

    de Vasconcellos, Jaira F.; Fasano, Ross M.; Lee, Y. Terry; Kaushal, Megha; Byrnes, Colleen; Meier, Emily R.; Anderson, Molly; Rabel, Antoinette; Braylan, Raul; Stroncek, David F.; Miller, Jeffery L.

    2014-01-01

    Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes. PMID:25188417

  9. Drosha mediates destabilization of Lin28 mRNA targets.

    PubMed

    Qiao, Chong; Ma, Jing; Xu, Jie; Xie, Mingyi; Ma, Wei; Huang, Yingqun

    2012-10-01

    Lin28 plays important roles in development, stem cell maintenance, oncogenesis and metabolism. As an RNA-binding protein, it blocks the biogenesis primarily of let-7 family miRNAs and also promotes translation of a cohort of mRNAs involved in cell growth, metabolism and pluripotency, likely through recognition of distinct sequence and structural motifs within mRNAs. Here, we show that one such motif, shared by multiple Lin28-responsive elements (LREs) present in Lin28 mRNA targets also participates in a Drosha-dependent regulation and may contribute to destabilization of its cognate mRNAs. We further show that the same mutations in the LREs known to abolish Lin28 binding and stimulation of translation also abrogate Drosha-dependent mRNA destabilization, and that this effect is independent of miRNAs, uncovering a previously unsuspected coupling between Drosha-dependent destabilization and Lin28-mediated regulation. Thus, Lin28-dependent stimulation of translation of target mRNAs may, in part, serve to compensate for their intrinsic instability, thereby ensuring optimal levels of expression of genes critical for cell viability, metabolism and pluripotency.

  10. The LIN28/let-7 Pathway in Cancer

    PubMed Central

    Balzeau, Julien; Menezes, Miriam R.; Cao, Siyu; Hagan, John P.

    2017-01-01

    Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function. For LIN28B, the precise mechanism responsible for let-7 inhibition remains controversial. Functionally, the decrease in let-7 microRNAs leads to overexpression of their oncogenic targets such as MYC, RAS, HMGA2, BLIMP1, among others. Furthermore, mouse models demonstrate that ectopic LIN28 expression is sufficient to drive and/or accelerate tumorigenesis via a let-7 dependent mechanism. In this review, the LIN28/let-7 pathway is discussed, emphasizing its role in tumorigenesis, cancer stem cell biology, metabolomics, metastasis, and resistance to ionizing radiation and several chemotherapies. Also, emerging evidence will be presented suggesting that molecular targeting of this pathway may provide therapeutic benefit in cancer. PMID:28400788

  11. Lin-28 regulates oogenesis and muscle formation in Drosophila melanogaster.

    PubMed

    Stratoulias, Vassilis; Heino, Tapio I; Michon, Frederic

    2014-01-01

    Understanding the control of stem cell (SC) differentiation is important to comprehend developmental processes as well as to develop clinical applications. Lin28 is a conserved molecule that is involved in SC maintenance and differentiation by regulating let-7 miRNA maturation. However, little is known about the in vivo function of Lin28. Here, we report critical roles for lin-28 during oogenesis. We found that let-7 maturation was increased in lin-28 null mutant fly ovaries. We showed that lin-28 null mutant female flies displayed reduced fecundity, due to defects in egg chamber formation. More specifically, we demonstrated that in mutant ovaries, the egg chambers fuse during early oogenesis resulting in abnormal late egg chambers. We also showed that this phenotype is the combined result of impaired germline SC differentiation and follicle SC differentiation. We suggest a model in which these multiple oogenesis defects result from a misregulation of the ecdysone signaling network, through the fine-tuning of Abrupt and Fasciclin2 expression. Our results give a better understanding of the evolutionarily conserved role of lin-28 on GSC maintenance and differentiation.

  12. LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer

    PubMed Central

    Permuth-Wey, Jennifer; Kim, Donghwa; Tsai, Ya-Yu; Lin, Hui-Yi; Chen, Y. Ann; Barnholtz-Sloan, Jill; Birrer, Michael J.; Bloom, Gregory; Chanock, Stephen J.; Chen, Zhihua; Cramer, Daniel W.; Cunningham, Julie M.; Dagne, Getachew; Ebbert-Syfrett, Judith; Fenstermacher, David; Fridley, Brooke L.; Garcia-Closas, Montserrat; Gayther, Simon A.; Ge, William; Gentry-Maharaj, Aleksandra; Gonzalez-Bosquet, Jesus; Goode, Ellen L.; Iversen, Edwin; Jim, Heather; Kong, William; McLaughlin, John; Menon, Usha; Monteiro, Alvaro N.A.; Narod, Steven A.; Pharoah, Paul D.P.; Phelan, Catherine M.; Qu, Xiaotao; Ramus, Susan J.; Risch, Harvey; Schildkraut, Joellen M.; Song, Honglin; Stockwell, Heather; Sutphen, Rebecca; Terry, Kathryn L.; Tyrer, Jonathan; Vierkant, Robert A.; Wentzensen, Nicolas; Lancaster, Johnathan M.; Cheng, Jin Q.; Sellers, Thomas A.

    2011-01-01

    Defective miRNA biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNPs) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P<0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), a SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR=0.90, 95% CI: 0.82–0.98; P=0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B over-expression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be due to reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility. PMID:21482675

  13. Lin-28 Regulates Oogenesis and Muscle Formation in Drosophila melanogaster

    PubMed Central

    Stratoulias, Vassilis; Heino, Tapio I.; Michon, Frederic

    2014-01-01

    Understanding the control of stem cell (SC) differentiation is important to comprehend developmental processes as well as to develop clinical applications. Lin28 is a conserved molecule that is involved in SC maintenance and differentiation by regulating let-7 miRNA maturation. However, little is known about the in vivo function of Lin28. Here, we report critical roles for lin-28 during oogenesis. We found that let-7 maturation was increased in lin-28 null mutant fly ovaries. We showed that lin-28 null mutant female flies displayed reduced fecundity, due to defects in egg chamber formation. More specifically, we demonstrated that in mutant ovaries, the egg chambers fuse during early oogenesis resulting in abnormal late egg chambers. We also showed that this phenotype is the combined result of impaired germline SC differentiation and follicle SC differentiation. We suggest a model in which these multiple oogenesis defects result from a misregulation of the ecdysone signaling network, through the fine-tuning of Abrupt and Fasciclin2 expression. Our results give a better understanding of the evolutionarily conserved role of lin-28 on GSC maintenance and differentiation. PMID:24963666

  14. Lin28 sustains early renal progenitors and induces Wilms tumor.

    PubMed

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S; Zhu, Hao; Perez-Atayde, Antonio R; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q

    2014-05-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis.

  15. Using Lin's method to solve Bykov's problems

    NASA Astrophysics Data System (ADS)

    Knobloch, Jürgen; Lamb, Jeroen S. W.; Webster, Kevin N.

    2014-10-01

    We consider nonwandering dynamics near heteroclinic cycles between two hyperbolic equilibria. The constituting heteroclinic connections are assumed to be such that one of them is transverse and isolated. Such heteroclinic cycles are associated with the termination of a branch of homoclinic solutions, and called T-points in this context. We study codimension-two T-points and their unfoldings in Rn. In our consideration we distinguish between cases with real and complex leading eigenvalues of the equilibria. In doing so we establish Lin's method as a unified approach to (re)gain and extend results of Bykov's seminal studies and related works. To a large extent our approach reduces the study to the discussion of intersections of lines and spirals in the plane. Case (RR): Under open conditions on the eigenvalues, there exist open sets in parameter space for which there exist periodic orbits close to the heteroclinic cycle. In addition, there exist two one-parameter families of homoclinic orbits to each of the saddle points p1 and p2.See Theorem 2.1 and Proposition 2.2 for precise statements and Fig. 2 for bifurcation diagrams. Cases (RC) and (CC): At the bifurcation point μ=0 and for each N≥2, there exists an invariant set S0N close to the heteroclinic cycle on which the first return map is topologically conjugated to a full shift on N symbols. For any fixed N≥2, the invariant set SμN persists for |μ| sufficiently small.In addition, there exist infinitely many transversal and non-transversal heteroclinic orbits connecting the saddle points p1 and p2 in a neighbourhood of μ=0, as well as infinitely many one-parameter families of homoclinic orbits to each of the saddle points.For full statements of the results see Theorem 2.3 and Propositions 2.4, 2.5 and Fig. 3 for bifurcation diagrams. The dynamics near T-points has been studied previously by Bykov [6-10], Glendinning and Sparrow [20], Kokubu [27,28] and Labouriau and Rodrigues [30,31,38]. See also the surveys

  16. Hepatitis B virus X protein upregulates Lin28A/Lin28B through Sp-1/c-Myc to enhance the proliferation of hepatoma cells.

    PubMed

    You, X; Liu, F; Zhang, T; Lv, N; Liu, Q; Shan, C; Du, Y; Kong, G; Wang, T; Ye, L; Zhang, X

    2014-01-23

    Hepatitis B virus X protein (HBx) plays critical roles in the pathogenesis of hepatocellular carcinoma (HCC). Here, we were interested in knowing whether the oncogene Lin28A and its homolog Lin28B are involved in the hepatocarcinogenesis mediated by HBx. We showed that the expression levels of Lin28A and Lin28B were increased in clinical HCC tissues, HepG2.2.15 cell line and liver tissues of p21-HBx transgenic mice. Interestingly, the expression levels of HBx were positively associated with those of Lin28A/Lin28B in clinical HCC tissues. Moreover, the overexpression of HBx resulted in the upregulation of Lin28A/Lin28B in hepatoma HepG2/H7402 cell lines by transient transfection, suggesting that HBx was able to upregulate Lin28A and Lin28B. Then, we examined the mechanism by which HBx upregulated Lin28A and Lin28B. We identified that the promoter region of Lin28A regulated by HBx was located at nt -235/-66 that contained Sp-1 binding element. Co-immunoprecipitation showed that HBx was able to interact with Sp-1 in HepG2-X cells. Moreover, chromatin immunoprecipitation (ChIP) demonstrated that HBx could bind to the promoter of Lin28A, which failed to work when Sp-1 was silenced. Electrophoretic mobility shift assay (EMSA) further identified that HBx was able to interact with Sp-1 element in Lin28A promoter via transcription factor Sp-1. In addition, we found that c-Myc was involved in the activation of Lin28B mediated by HBx. In function, Lin28A/Lin28B played important roles in HBx-enhanced proliferation of hepatoma cells in vitro and in vivo. In conclusion, HBx activates Lin28A/Lin28B through Sp-1/c-Myc in hepatoma cells. Lin28A/Lin28B serves as key driver genes in HBx-induced hepatocarcinogenesis.

  17. A Command Editor Tool for NEXTSTEP

    DTIC Science & Technology

    1993-07-01

    appears and presents the hierarchy of CEMenuCells A Command Editor Tool for NEXTSTEP 2 of 27 m arble Final Report for Contract # DAAHO1-93-C-R013 in the...icon, "Default" status, state list, textual description, tool sta- A Command Editor Tool for NEXTSTEP 3 of 27 m arble Final Report for Contract... arble Final Report for Contract # DAAH01-93-C-R013 FIGURE 7 Configuration of a TAV 3.0.. Acietr O ev 3.1 luBman d aetn Cmoe a ConQ summw t. Paletta e

  18. EDITORIAL: Letter from the Editor

    NASA Astrophysics Data System (ADS)

    Hauptmann, Peter

    2006-12-01

    Dear authors and reviewers of articles for Measurement Science and Technology, I would like to thank all those who have published papers with us in 2006, and special thanks go to those of you who have kindly reviewed articles for the journal this year. I would also like to take this opportunity to update you on some of the developments on the journal this year. As many of you are no doubt aware our impact factor (a measure of the average number of times recent papers are referred to by others) has remained above 1 for the second year in a row. This is often taken as an indication of the quality and relevance of recently published research, and although as readers we develop our own instinct for journals of high quality, it is gratifying as an Editor to see the data from an independent organization agreeing with my own assessment. This year we have welcomed several new faces to our Editorial Board and International Advisory Board. We are delighted to welcome Professor Hirofumi Yamada of the University of Kyoto as a representative from Japan. From China we have been joined by Professor Xuzong Chen of Peking University and Professor Zhiyi Wei of Chinese Academy of Sciences, Beijing. Professor Ivan Marusic from University of Minnesota and Dr Paul Williams of the National Institute of Standards and Technology in Boulder have joined as North American representatives. As usual you will be able to submit your articles through them or direct to the Editorial Office in Bristol, UK. As part of our ongoing initiative to give our authors' work the highest visibility, all articles are freely available online for 30 days from the date of publication, allowing all researchers to read and view the latest research as soon as it is published, and this year there have been many interesting articles to read! As regular readers are aware, Measurement Science and Technology publishes special issues and features, which highlight an area of current interest. This year's topics included

  19. Stepwise enhancement of catalytic performance of haloalkane dehalogenase LinB towards β-hexachlorocyclohexane

    PubMed Central

    2014-01-01

    Two haloalkane dehalogenases, LinBUT and LinBMI, each with 296 amino acid residues, exhibit only seven amino acid residue differences between them, but LinBMI’s catalytic performance towards β-hexachlorocyclohexane (β-HCH) is considerably higher than LinBUT’s. To elucidate the molecular basis governing this difference, intermediate mutants between LinBUT and LinBMI were constructed and kinetically characterized. The activities of LinBUT-based mutants gradually increased by cumulative mutations into LinBUT, and the effects of the individual amino acid substitutions depended on combination with other mutations. These results indicated that LinBUT’s β-HCH degradation activity can be enhanced in a stepwise manner by the accumulation of point mutations. PMID:25401073

  20. LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency.

    PubMed

    Zhang, Jin; Ratanasirintrawoot, Sutheera; Chandrasekaran, Sriram; Wu, Zhaoting; Ficarro, Scott B; Yu, Chunxiao; Ross, Christian A; Cacchiarelli, Davide; Xia, Qing; Seligson, Marc; Shinoda, Gen; Xie, Wen; Cahan, Patrick; Wang, Longfei; Ng, Shyh-Chang; Tintara, Supisara; Trapnell, Cole; Onder, Tamer; Loh, Yuin-Han; Mikkelsen, Tarjei; Sliz, Piotr; Teitell, Michael A; Asara, John M; Marto, Jarrod A; Li, Hu; Collins, James J; Daley, George Q

    2016-07-07

    The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Open Simulation Laboratories [Guest editors' introduction

    SciTech Connect

    Alexander, Francis J.; Meneveau, Charles

    2015-09-01

    The introduction for the special issue on open simulation laboratories, the guest editors describe how OSLs will become more common as their potential is better understood and they begin providing access to valuable datasets to much larger segments of the scientific community. Moreover, new analysis tools and ways to do science will inevitably develop as a result.

  2. Open Simulation Laboratories [Guest editors' introduction

    DOE PAGES

    Alexander, Francis J.; Meneveau, Charles

    2015-09-01

    The introduction for the special issue on open simulation laboratories, the guest editors describe how OSLs will become more common as their potential is better understood and they begin providing access to valuable datasets to much larger segments of the scientific community. Moreover, new analysis tools and ways to do science will inevitably develop as a result.

  3. Are Editors Out of the Tenure Process?

    ERIC Educational Resources Information Center

    Howard, Jennifer

    2007-01-01

    University presses have complained for years that tenure committees unfairly expect their editors to be arbiters of what counts as tenure-worthy work. At the same time, the presses have been caught in a business-side squeeze between dwindling sales (and shrinking subsidies) and the ever-greater pressure on scholars to publish. In this article, the…

  4. Editors, Teachers Disagree about Definition of Plagiarism.

    ERIC Educational Resources Information Center

    Chaney, Jerry; Duncan, Tom

    1985-01-01

    Describes a study of plagiarism policies in journalism schools and newsrooms. Concludes that instructors felt educating students about plagiarism was one of the most important services journalism schools offer, but editors felt that plagiarism standards must be set in the real world of the newsroom. (HTH)

  5. A Visual Editor in Java for View

    NASA Technical Reports Server (NTRS)

    Stansifer, Ryan

    2000-01-01

    In this project we continued the development of a visual editor in the Java programming language to create screens on which to display real-time data. The data comes from the numerous systems monitoring the operation of the space shuttle while on the ground and in space, and from the many tests of subsystems. The data can be displayed on any computer platform running a Java-enabled World Wide Web (WWW) browser and connected to the Internet. Previously a special-purpose program bad been written to display data on emulations of character-based display screens used for many years at NASA. The goal now is to display bit-mapped screens created by a visual editor. We report here on the visual editor that creates the display screens. This project continues the work we bad done previously. Previously we had followed the design of the 'beanbox,' a prototype visual editor created by Sun Microsystems. We abandoned this approach and implemented a prototype using a more direct approach. In addition, our prototype is based on newly released Java 2 graphical user interface (GUI) libraries. The result has been a visually more appealing appearance and a more robust application.

  6. Are Editors Out of the Tenure Process?

    ERIC Educational Resources Information Center

    Howard, Jennifer

    2007-01-01

    University presses have complained for years that tenure committees unfairly expect their editors to be arbiters of what counts as tenure-worthy work. At the same time, the presses have been caught in a business-side squeeze between dwindling sales (and shrinking subsidies) and the ever-greater pressure on scholars to publish. In this article, the…

  7. Research Writing and NNSs: From the Editors.

    ERIC Educational Resources Information Center

    Gosden, Hugh

    1992-01-01

    Varied linguistic and sociopragmatic skills required for effective international research reporting are discussed based on a survey of journal editors in North America and the United Kingdom. Emphasis is on language-related criteria that influence publication decisions, and suggestions are offered for teaching research writing. (17 references)…

  8. OPM Scheme Editor 2: A graphical editor for specifying object-protocol structures

    SciTech Connect

    Chen, I-Min A.; Markowitz, V.M.; Pang, F.; Ben-Shachar, O.

    1993-07-01

    This document describes an X-window based Schema Editor for the Object-Protocol Model (OPM). OPM is a data model that supports the specification of complex object and protocol classes. objects and protocols are qualified in OPM by attributes that are defined over (associated with) value classes. Connections of object and protocol classes are expressed in OPM via attributes. OPM supports the specification (expansion) of protocols in terms of alternative and sequences of component (sub) protocols. The OPM Schema Editor allows specifying, displaying, modifying, and browsing through OPM schemas. The OPM Schema Editor generates an output file that can be used as input to an OPM schema translation tool that maps OPM schemas into definitions for relational database management systems. The OPM Schema Editor was implemented using C++ and the X11 based Motif toolkit, on Sun SPARCstation under Sun Unix OS 4.1. This document consists of the following parts: (1) A tutorial consisting of seven introductory lessons for the OPM Schema Editor. (2) A reference manual describing all the windows and functions of the OPM Schema Editor. (3) An appendix with an overview of OPM.

  9. Advice for a young editor: the scientific publication.

    PubMed

    Turpin, David L

    2005-01-01

    Being the editor of a scientific journal involves the same challenges of working with authors, association officers, and readers as in all publications. In addition to the communication in the journal, editors must manage the communication about the journal. The editor's job involves building and maintaining trust.

  10. Editor and Student Views on the Censorship Game.

    ERIC Educational Resources Information Center

    Raburn, Josephine

    Out of 200 newspaper editors randomly selected from a directory, 64 responded to a questionnaire eliciting their opinions on the subject materials most often censored by groups in the United States. The editors' responses were compared to those of 121 freshmen at Cameron University (Oklahoma). A majority of the editors supported the First…

  11. Lin28 and let-7 in cell metabolism and cancer.

    PubMed

    Nguyen, Liem H; Zhu, Hao

    2015-01-01

    Malignant cells exhibit major metabolic alterations. The regulatory gene networks that regulate metabolism and the impact of these alterations on overall cellular fitness deserve further exploration. The let-7 microRNAs and their antagonists, the Lin28 RNA-binding proteins, are well-known for controlling the timing of embryonic development. This pathway has recently been shown to regulate glucose metabolism in adult mice and to reprogram metabolism during tissue injury and repair. In addition, many lines of evidence have established that Lin28 is an oncogene that drives tumorigenesis in part by suppressing let-7. The metabolic underpinnings of this oncogenic program are just beginning to be uncovered. Here, we will review the current understanding of how Lin28 exerts regenerative and oncogenic effects through metabolic mechanisms.

  12. Lin28 and let-7 in cell metabolism and cancer

    PubMed Central

    Nguyen, Liem H.

    2015-01-01

    Malignant cells exhibit major metabolic alterations. The regulatory gene networks that regulate metabolism and the impact of these alterations on overall cellular fitness deserve further exploration. The let-7 microRNAs and their antagonists, the Lin28 RNA-binding proteins, are well-known for controlling the timing of embryonic development. This pathway has recently been shown to regulate glucose metabolism in adult mice and to reprogram metabolism during tissue injury and repair. In addition, many lines of evidence have established that Lin28 is an oncogene that drives tumorigenesis in part by suppressing let-7. The metabolic underpinnings of this oncogenic program are just beginning to be uncovered. Here, we will review the current understanding of how Lin28 exerts regenerative and oncogenic effects through metabolic mechanisms. PMID:26835354

  13. Evolutionary theory in letters to the editor.

    PubMed

    Silva, Eric Orion; Lowe, Clayton Cory

    2015-05-01

    This research note presents the results of a content analysis of 234 letters to the editors that discuss evolutionary theory and were published in American newspapers. We find that letters to the editor both support and hinder the cause of teaching evolutionary theory in American secondary schools. On the one hand, anti-evolutionary theory messages are marginalized in the letters section. This marginalization signals a low level of legitimacy for creationism. It might also contribute to the sense of tension that sustains creationist identities. On the other hand, relatively few letters explicitly note the fact that scientists or the scientific community accept evolution. Interestingly, the obscuration of the scientific community's support for evolutionary theory occurs both in letters supporting and opposing evolutionary theory.

  14. Unified Meta-Component Model Specification Editor

    DTIC Science & Technology

    2004-04-20

    relationship between the two major user interface modules, the editor and wizard, and their associated features. Functional to module mapping diagrams are...SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18 . NUMBER OF PAGES 148 19a. NAME OF RESPONSIBLE...PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39- 18

  15. Workbench surface editor of brain cortical surface

    NASA Astrophysics Data System (ADS)

    Dow, Douglas E.; Nowinski, Wieslaw L.; Serra, Luis

    1996-04-01

    We have developed a 3D reach-in tool to manually reconstruct 3D cortical surface patches from 2D brain atlas images. The first application of our cortex editor is building 3D functional maps, specifically Brodmann's areas. This tool may also be useful in clinical practice to adjust incorrectly mapped atlas regions due to the deforming effect of lesions. The cortex editor allows a domain expert to control the correlation of control points across slices. Correct correlation has been difficult for 3D reconstruction algorithms because the atlas slices are far apart and because of the complex topology of the cortex which differs so much from slice to slice. Also, higher precision of the resulting surfaces is demanded since these define 3D brain atlas features upon which future stereotactic surgery may be based. The cortex editor described in this paper provides a tool suitable for a domain expert to use in defining the 3D surface of a Brodmann's area.

  16. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors and its effects on the hallmarks of cancer.

    PubMed

    Wang, Tianzhen; Wang, Guangyu; Hao, Dapeng; Liu, Xi; Wang, Dong; Ning, Ning; Li, Xiaobo

    2015-06-30

    RNA binding proteins (RBPs) and microRNAs (miRNAs) are two of the most important post-transcriptional regulators of gene expression, and their aberrant expression contributes to the development of human malignancies. Let-7, one of the most well-known tumor suppressors, is frequently down-regulated in a variety of human cancers. The RBP LIN28A/LIN28B, a direct target of the let-7 family of miRNAs, is an inhibitor of let-7 biogenesis and is frequently up-regulated in cancers. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors is reportedly involved in cancer development, contributing to cellular proliferation, cell death resistance, angiogenesis, metastasis, metabolism reprogramming, tumor-associated inflammation, genome instability, acquiring immortality and evading immune destruction. In this review, we summarized the mechanisms of LIN28A/LIN28B and let-7 loop aberrant regulation in human cancer and discussed the roles and potential mechanisms of the LIN28A/LIN28B and let-7 loop in regulating the hallmarks of cancer. The crosstalk between LIN28A/LIN28B and let-7 loop and certain oncogenes (such as MYC, RAS, PI3K/AKT, NF-κB and β-catenin) in regulating hallmarks of cancer has also been discussed.

  17. Sex-specific regulation of weight and puberty by the Lin28/let-7 axis.

    PubMed

    Corre, Christina; Shinoda, Gen; Zhu, Hao; Cousminer, Diana L; Crossman, Christine; Bellissimo, Christian; Goldenberg, Anna; Daley, George Q; Palmert, Mark R

    2016-03-01

    Growth and pubertal timing differ in boys and girls. Variants in/near LIN28B associate with age at menarche (AAM) in genome-wide association studies and some AAM-related variants associate with growth in a sex-specific manner. Sex-specific growth patterns in response to Lin28b perturbation have been detected in mice, and overexpression of Lin28a has been shown to alter pubertal timing in female mice. To investigate further how Lin28a and Lin28b affect growth and puberty in both males and females, we evaluated Lin28b loss-of-function (LOF) mice and Lin28a gain-of-function (GOF) mice. Because both Lin28a and Lin28b can act via the conserved microRNA let-7, we also examined let-7 GOF mice. As reported previously, Lin28b LOF led to lighter body weights only in male mice while Lin28a GOF yielded heavier mice of both sexes. Let-7 GOF mice weighed less than controls, and males were more affected than females. Timing of puberty was assessed by vaginal opening (VO) and preputial separation (PS). Male Lin28b LOF and male let-7 GOF, but not female, mice displayed alteration of pubertal timing, with later PS than controls. In contrast, both male and female Lin28a GOF mice displayed late onset of puberty. Together, these data point toward a complex system of regulation by Lin28a, Lin28b, and let-7, in which Lin28b and let-7 can impact both puberty and growth in a sex-specific manner, raising the possibility that this pathway may contribute to differential regulation of male and female growth and puberty in humans. © 2016 Society for Endocrinology.

  18. New “Editor's choice”: Online journals debut

    NASA Astrophysics Data System (ADS)

    Cole, Stephen

    With all AGU journal articles now published online in advance of the printed journal, AGU members have new options, in terms of how they access the latest research results. An innovative option for those with specific research interests that are covered in several journals is the " Editor's Choice" virtual journal. The first two "Editor's Choice" journals—Biogeosciences and Atmospheric Electricity— debuted in January and are, for a limited time, freely accessible to members on the AGU Web site.An "Editor's Choice" virtual journal is a collection of electronic articles recently published by AGU that have been specially selected for their relevance to a particular topic area. Everett Shock of Washington University St. Louis, is serving as the Collection Editor for "Editor's Choice: Biogeosciences." The "Editor's Choice: Atmospheric Electricity" Collection Editor is Richard E. Orville of Texas A&M University College Station, who is being assisted by advisors David Sentman, University of Alaska, and Vladimir Rakov, University of Florida.

  19. Lin28 promotes the proliferative capacity of neural progenitor cells in brain development

    PubMed Central

    Yang, Mei; Yang, Si-Lu; Herrlinger, Stephanie; Liang, Chen; Dzieciatkowska, Monika; Hansen, Kirk C.; Desai, Ridham; Nagy, Andras; Niswander, Lee; Moss, Eric G.; Chen, Jian-Fu

    2015-01-01

    Neural progenitor cells (NPCs) have distinct proliferation capacities at different stages of brain development. Lin28 is an RNA-binding protein with two homologs in mice: Lin28a and Lin28b. Here we show that Lin28a/b are enriched in early NPCs and their expression declines during neural differentiation. Lin28a single-knockout mice show reduced NPC proliferation, enhanced cell cycle exit and a smaller brain, whereas mice lacking both Lin28a alleles and one Lin28b allele display similar but more severe phenotypes. Ectopic expression of Lin28a in mice results in increased NPC proliferation, NPC numbers and brain size. Mechanistically, Lin28a physically and functionally interacts with Imp1 (Igf2bp1) and regulates Igf2-mTOR signaling. The function of Lin28a/b in NPCs could be attributed, at least in part, to the regulation of their mRNA targets that encode Igf1r and Hmga2. Thus, Lin28a and Lin28b have overlapping functions in temporally regulating NPC proliferation during early brain development. PMID:25922525

  20. Lin28 promotes the proliferative capacity of neural progenitor cells in brain development.

    PubMed

    Yang, Mei; Yang, Si-Lu; Herrlinger, Stephanie; Liang, Chen; Dzieciatkowska, Monika; Hansen, Kirk C; Desai, Ridham; Nagy, Andras; Niswander, Lee; Moss, Eric G; Chen, Jian-Fu

    2015-05-01

    Neural progenitor cells (NPCs) have distinct proliferation capacities at different stages of brain development. Lin28 is an RNA-binding protein with two homologs in mice: Lin28a and Lin28b. Here we show that Lin28a/b are enriched in early NPCs and their expression declines during neural differentiation. Lin28a single-knockout mice show reduced NPC proliferation, enhanced cell cycle exit and a smaller brain, whereas mice lacking both Lin28a alleles and one Lin28b allele display similar but more severe phenotypes. Ectopic expression of Lin28a in mice results in increased NPC proliferation, NPC numbers and brain size. Mechanistically, Lin28a physically and functionally interacts with Imp1 (Igf2bp1) and regulates Igf2-mTOR signaling. The function of Lin28a/b in NPCs could be attributed, at least in part, to the regulation of their mRNA targets that encode Igf1r and Hmga2. Thus, Lin28a and Lin28b have overlapping functions in temporally regulating NPC proliferation during early brain development. © 2015. Published by The Company of Biologists Ltd.

  1. Lin28a--boost your energy for youthful regeneration.

    PubMed

    Burkhalter, Martin D; Morita, Yohei; Rudolph, Karl Lenhard

    2014-01-07

    The regenerative capacity of most tissues declines dramatically after embryonic development and during post-natal life. The underlying mechanisms of this phenomenon are incompletely understood. In a recent issue of Cell, Shyh-Chang and colleagues provide experimental evidence that Lin28 prolongs youthful regenerative capacity by increasing oxidative glucose metabolism (Shyh-Chang et al, 2013).

  2. 75 FR 842 - Action Affecting Export Privileges: Hailin Lin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-06

    ... case. \\2\\ 50 U.S.C. app. Sec. Sec. 2401-2420 (2000). Since August 21, 2001, the Act has been in lapse... (the ``Regulations''),\\1\\ and Section 13(c) of the Export Administration Act of 1979, as amended (the ``Act''),\\2\\ through the issuance of a charging letter to Lin that alleged that she committed 124...

  3. From the Board of Editors: on Plagiarism

    NASA Astrophysics Data System (ADS)

    2005-04-01

    From the Board of Editors: on Plagiarism

    Dear Colleagues: There has been a significant increase in the number of duplicate submissions and plagiarism cases reported in all major journals, including the journals of the Optical Society of America. Duplicate submissions and plagiarism can take many forms, and all of them are violations of professional ethics, the copyright agreement that an author signs along with the submission of a paper, and OSA's published Author Guidelines. There must be a significant component of new science for a paper to be publishable. The copying of large segments of text from previously published or in-press papers with only minor cosmetic changes is not acceptable and can lead to the rejection of papers. Duplicate submission: Duplicate submission is the most common ethics violation encountered. Duplicate submission is the submission of substantially similar papers to more than one journal. There is a misperception in a small fraction of the scientific community that duplicate submission is acceptable because it sometimes takes a long time to get a paper reviewed and because one of the papers can be withdrawn at any time. This is a clear violation of professional ethics and of the copyright agreement that is signed on submission. Duplicate submission harms the whole community because editors and reviewers waste their time and in the process compound the time it takes to get a paper reviewed for all authors. In cases of duplicate submission, the Editor of the affected OSA journal will consult with the Editor of the other journal involved to determine the proper course of action. Often that action will be the rejection of both papers. Plagiarism: Plagiarism is a serious breach of ethics and is defined as the substantial replication, without attribution, of significant elements of another document already published by the same or other authors. Two types of plagiarism can occur

  4. Performance of a prototype atomic clock based on lin parallel lin coherent population trapping resonances in Rb atomic vapor

    SciTech Connect

    Mikhailov, Eugeniy E.; Horrom, Travis; Belcher, Nathan; Novikova, Irina

    2010-03-15

    We report on the performance of the first table-top prototype atomic clock based on coherent population trapping (CPT) resonances with parallel linearly polarized optical fields (lin parallel lin configuration). Our apparatus uses a vertical-cavity surface-emitting laser (VCSEL) tuned to the D{sub 1} line of {sup 87}Rb with the current modulation at the {sup 87}Rb hyperfine frequency. We demonstrate cancellation of the first-order light shift by the proper choice of rf modulation power and further improve our prototype clock stability by optimizing the parameters of the microwave lock loop. Operating in these optimal conditions, we measured a short-term fractional frequency stability (Allan deviation) 2x10{sup -11}{tau}{sup -1/2} for observation times 1 s{<=}{tau}{<=}20 s. This value is limited by large VCSEL phase noise and environmental temperature fluctuation. Further improvements in frequency stability should be possible with an apparatus designed as a dedicated lin parallel lin CPT resonance clock with environmental impacts minimized.

  5. Lin28: Primal Regulator of Growth and Metabolism in Stem Cells

    PubMed Central

    Shyh-Chang, Ng; Daley, George Q.

    2013-01-01

    In recent years, the highly conserved Lin28 RNA-binding proteins have emerged as factors that define stemness in several tissue lineages. Lin28 proteins repress let-7 microRNAs and influence mRNA translation, thereby regulating the self-renewal of mammalian embryonic stem cells. Subsequent discoveries revealed that Lin28a and Lin28b are also important in organismal growth and metabolism, tissue development, somatic reprogramming and cancer. In this Review, we discuss the Lin28 pathway and its regulation, outline its roles in stem cells, tissue development, and pathogenesis, and examine the ramifications for re-engineering mammalian physiology. PMID:23561442

  6. Beyond an oncogene, Lin28 is a master regulator of cancer progression.

    PubMed

    Wang, Xuefei; Weng, Mingjiao; Jin, Yinji; Yang, Weiwei; Wang, Xin; Wu, Di; Wang, Tianzhen; Li, Xiaobo

    2017-07-26

    The RNA binding protein Lin28 is increased in most human malignancies, and elevated Lin28 is a biomarker for poor prognosis and contributes to cancer progression. Lin28 functions as a master oncogene and is involved in almost all hallmarks of cancer. In this review, we summarize the aberrant molecular expression mechanisms and pathological roles of Lin28 in cancer progression. Moreover, we elaborate on the established molecular mechanisms, from the transcriptional level to the post-transcriptional and translational levels, by which Lin28 regulates cancer progression.

  7. Meet the Editor: Global Biogeochemical Cycles

    NASA Astrophysics Data System (ADS)

    Kumar, Mohi

    Meinrat Andreae was named the editor of the AGU's journal Global Biogeochemical Cycles last year.Andreae, director of the biogeochemistry department at the Max Plank Institute for Chemistry (MPIC), located in Mainz, Germany said that he plans to maintain the journal as a resource that highlights the broad spectrum of interdisciplinary themes that showcase the interactions between the biosphere and the geosphere. “Our special niche is in the field of larger-scale, more integrative studies that have global scope,” he explained.

  8. MPS Editor - An Integrated Sequencing Environment

    NASA Technical Reports Server (NTRS)

    Streiffert, Barbara A.; O'Reilly, Taifun; Schrock, Mitchell; Catchen, Jaime

    2010-01-01

    In today's operations environment, the teams are smaller and need to be more efficient while still ensuring the safety and success of the mission. In addition, teams often begin working on a mission in its early development phases and continue on the team through actual operations. For these reasons the operations teams want to be presented with a software environment that integrates multiple needed software applications as well as providing them with context sensitive editing support for entering commands and sequences of commands. At Jet Propulsion Laboratory, the Multi-Mission Planning and Sequencing (MPS) Editor provided by the Multi-Mission Ground Systems and Services (MGSS) supports those operational needs.

  9. MPS Editor - An Integrated Sequencing Environment

    NASA Technical Reports Server (NTRS)

    Streiffert, Barbara A.; O'Reilly, Taifun; Schrock, Mitchell; Catchen, Jaime

    2010-01-01

    In today's operations environment, the teams are smaller and need to be more efficient while still ensuring the safety and success of the mission. In addition, teams often begin working on a mission in its early development phases and continue on the team through actual operations. For these reasons the operations teams want to be presented with a software environment that integrates multiple needed software applications as well as providing them with context sensitive editing support for entering commands and sequences of commands. At Jet Propulsion Laboratory, the Multi-Mission Planning and Sequencing (MPS) Editor provided by the Multi-Mission Ground Systems and Services (MGSS) supports those operational needs.

  10. From the Board of Editors: on Plagiarism

    NASA Astrophysics Data System (ADS)

    2005-03-01

    Dear Colleagues: There has been a significant increase in the number of duplicate submissions and plagiarism cases reported in all major journals, including the journals of the Optical Society of America. Duplicate submissions and plagiarism can take many forms, and all of them are violations of professional ethics, the copyright agreement that an author signs along with the submission of a paper, and OSA's published Author Guidelines. There must be a significant component of new science for a paper to be publishable. The copying of large segments of text from previously published or in-press papers with only minor cosmetic changes is not acceptable and can lead to the rejection of papers. Duplicate submission is the most common ethics violation encountered. Duplicate submission is the submission of substantially similar papers to more than one journal. There is a misperception in a small fraction of the scientific community that duplicate submission is acceptable because it sometimes takes a long time to get a paper reviewed and because one of the papers can be withdrawn at any time. This is a clear violation of professional ethics and of the copyright agreement that is signed on submission. Duplicate submission harms the whole community because editors and reviewers waste their time and in the process compound the time it takes to get a paper reviewed for all authors. In cases of duplicate submission, the Editor of the affected OSA journal will consult with the Editor of the other journal involved to determine the proper course of action. Often that action will be the rejection of both papers. Plagiarism: Plagiarism is a serious breach of ethics and is defined as the substantial replication, without attribution, of significant elements of another document already published by the same or other authors. Two types of plagiarism can occur-self-plagiarism and plagiarism from others' works. Self-plagiarism is the publication of substantially similar scientific content

  11. lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development.

    PubMed

    Warrander, Fiona; Faas, Laura; Kovalevskiy, Oleg; Peters, Daniel; Coles, Mark; Antson, Alfred A; Genever, Paul; Isaacs, Harry V

    2016-01-01

    Lin28 proteins are post-transcriptional regulators of gene expression with multiple roles in development and the regulation of pluripotency in stem cells. Much attention has focussed on Lin28 proteins as negative regulators of let-7 miRNA biogenesis; a function that is conserved in several animal groups and in multiple processes. However, there is increasing evidence that Lin28 proteins have additional roles, distinct from regulation of let-7 abundance. We have previously demonstrated that lin28 proteins have functions associated with the regulation of early cell lineage specification in Xenopus embryos, independent of a lin28/let-7 regulatory axis. However, the nature of lin28 targets in Xenopus development remains obscure. Here, we show that mir-17∼92 and mir-106∼363 cluster miRNAs are down-regulated in response to lin28 knockdown, and RNAs from these clusters are co-expressed with lin28 genes during germ layer specification. Mature miRNAs derived from pre-mir-363 are most sensitive to lin28 inhibition. We demonstrate that lin28a binds to the terminal loop of pre-mir-363 with an affinity similar to that of let-7, and that this high affinity interaction requires to conserved a GGAG motif. Our data suggest a novel function for amphibian lin28 proteins as positive regulators of mir-17∼92 family miRNAs. © 2015 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc.

  12. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms.

    PubMed

    Feng, Chen; Neumeister, Veronique; Ma, Wei; Xu, Jie; Lu, Lingeng; Bordeaux, Jennifer; Maihle, Nita J; Rimm, David L; Huang, Yingqun

    2012-07-01

    The RNA binding protein Lin28 and its paralog Lin28B are associated with advanced human malignancies. Blocking the biogenesis of let-7 miRNA, a tumor suppressor, by Lin28/Lin28B has been thought to underlie their roles in cancer. Here we report that the mRNA for the human epidermal growth factor receptor 2 (HER2), a HER-family receptor tyrosine kinase known to play a critical role in cell proliferation and survival and also a major therapeutic target in breast cancer, is among several targets of Lin28 regulation. We show that Lin28 stimulates HER2 expression at the posttranscriptional level, and that enforced Lin28 expression promotes cancer cell growth via multiple mechanisms. Consistent with its pleiotropic role in regulating gene expression, Lin28 overexpression in primary breast tumors is a powerful predictor of poor prognosis, representing the first report on the impact of Lin28 expression on clinical outcome in human cancer. While revealing another layer of regulation of HER2 expression in addition to gene amplification, our studies also suggest novel mechanistic insights linking Lin28 expression to disease outcome and imply that targeting multiple pathways is a common mechanistic theme of Lin28-mediated regulation in cancer.

  13. lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development

    PubMed Central

    Warrander, Fiona; Faas, Laura; Kovalevskiy, Oleg; Peters, Daniel; Coles, Mark; Antson, Alfred A.; Genever, Paul

    2015-01-01

    Background: Lin28 proteins are post‐transcriptional regulators of gene expression with multiple roles in development and the regulation of pluripotency in stem cells. Much attention has focussed on Lin28 proteins as negative regulators of let‐7 miRNA biogenesis; a function that is conserved in several animal groups and in multiple processes. However, there is increasing evidence that Lin28 proteins have additional roles, distinct from regulation of let‐7 abundance. We have previously demonstrated that lin28 proteins have functions associated with the regulation of early cell lineage specification in Xenopus embryos, independent of a lin28/let‐7 regulatory axis. However, the nature of lin28 targets in Xenopus development remains obscure. Results: Here, we show that mir‐17∼92 and mir‐106∼363 cluster miRNAs are down‐regulated in response to lin28 knockdown, and RNAs from these clusters are co‐expressed with lin28 genes during germ layer specification. Mature miRNAs derived from pre‐mir‐363 are most sensitive to lin28 inhibition. We demonstrate that lin28a binds to the terminal loop of pre‐mir‐363 with an affinity similar to that of let‐7, and that this high affinity interaction requires to conserved a GGAG motif. Conclusions: Our data suggest a novel function for amphibian lin28 proteins as positive regulators of mir‐17∼92 family miRNAs. Developmental Dynamics 245:34–46, 2016. © 2015 Wiley Periodicals, Inc. PMID:26447465

  14. Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway.

    PubMed

    Sun, Shuhong; Zhang, Mingming; Lin, Jie; Hu, Jianqiang; Zhang, Rongqing; Li, Congye; Wei, Tianlu; Sun, Dongdong; Wei, Jianqin; Wang, Haichang

    2016-01-01

    Lin28a enhances glucose uptake and insulin-sensitivity. However, the role of Lin28a on experimental diabetic cardiomyopathy (DCM) is not well understood. We investigated the potential role and mechanism ofLin28a in diabetes-induced myocardial dysfunction in mice. Diabetes was induced by intraperitoneal (i.p.) injections of Streptozocin (STZ) in mice. Animals were randomized to be treated with lentivirus carrying Lin28a siRNA or Lin28a cDNA. Cardiac function, cardiomyocyte autophagy, apoptosis and mitochondria morphology in diabetic mice were compared between groups. The target proteins of Lin28a were examined by western blot analysis. Lin28a levels were markedly reduced in the cardiac tissue compared to the control mice. Lin28a overexpression significantly improved left ventricular ejection fraction (LVEF), promoted autophagy, decreased myocardial apoptotic index and alleviated mitochondria cristae destruction in diabetic mice. Lin28a knockdown exacerbated diabetic injury as evidenced by decreased LVEF, increased apoptotic index and aggravated mitochondria cristae destruction. Interestingly, pretreatment with a PKA inhibitor, N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide], di-HCl Salt (H89) abolished the beneficial effects of Lin28a overexpression. RhoA-expression and ROCK2-expression were decreased in vivo after Lin28a overexpression, while Lin28a knockdown increased the expression of RhoA and ROCK2 in diabetic mice. Lin28a protects against DCM through PKA/ROCK2 dependent pathway. Lin28a might serve as a potential therapeutic target for the treatment of the patients with DCM. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Lin28 proteins are required for germ layer specification in Xenopus.

    PubMed

    Faas, Laura; Warrander, Fiona C; Maguire, Richard; Ramsbottom, Simon A; Quinn, Diana; Genever, Paul; Isaacs, Harry V

    2013-03-01

    Lin28 family proteins share a unique structure, with both zinc knuckle and cold shock RNA-binding domains, and were originally identified as regulators of developmental timing in Caenorhabditis elegans. They have since been implicated as regulators of pluripotency in mammalian stem cells in culture. Using Xenopus tropicalis, we have undertaken the first analysis of the effects on the early development of a vertebrate embryo resulting from global inhibition of the Lin28 family. The Xenopus genome contains two Lin28-related genes, lin28a and lin28b. lin28a is expressed zygotically, whereas lin28b is expressed both zygotically and maternally. Both lin28a and lin28b are expressed in pluripotent cells of the Xenopus embryo and are enriched in cells that respond to mesoderm-inducing signals. The development of axial and paraxial mesoderm is severely abnormal in lin28 knockdown (morphant) embryos. In culture, the ability of pluripotent cells from the embryo to respond to the FGF and activin/nodal-like mesoderm-inducing pathways is compromised following inhibition of lin28 function. Furthermore, there are complex effects on the temporal regulation of, and the responses to, mesoderm-inducing signals in lin28 morphant embryos. We provide evidence that Xenopus lin28 proteins play a key role in choreographing the responses of pluripotent cells in the early embryo to the signals that regulate germ layer specification, and that this early function is probably independent of the recognised role of Lin28 proteins in negatively regulating let-7 miRNA biogenesis.

  16. Hypothalamic Ventromedial Lin28a Enhances Glucose Metabolism in Diet-Induced Obesity.

    PubMed

    Kim, Jung Dae; Toda, Chitoku; Ramírez, Cristina M; Fernández-Hernando, Carlos; Diano, Sabrina

    2017-08-01

    The Lin28a/Let-7 axis has been studied in peripheral tissues for its role in metabolism regulation. However, its central function remains unclear. Here we found that Lin28a is highly expressed in the hypothalamus compared with peripheral tissues. Its expression is positively correlated with positive energy balance, suggesting a potential central role for Lin28a in metabolism regulation. Thus, we targeted the hypothalamic ventromedial nucleus (VMH) to selectively overexpress (Lin28aKI(VMH) ) or downregulate (Lin28aKD(VMH) ) Lin28a expression in mice. With mice on a standard chow diet, body weight and glucose homeostasis were not affected in Lin28aKI(VMH) or Lin28aKD(VMH) mice. On a high-fat diet, although no differences in body weight and composition were observed, Lin28aKI(VMH) mice showed improved glucose tolerance and insulin sensitivity compared with controls. Conversely, Lin28aKD(VMH) mice displayed glucose intolerance and insulin resistance. Changes in VMH AKT activation of diet-induced obese Lin28aKI(VMH) or Lin28aKD(VMH) mice were not associated with alterations in Let-7 levels or insulin receptor activation. Rather, we observed altered expression of TANK-binding kinase-1 (TBK-1), which was found to be a direct Lin28a target mRNA. VMH-specific inhibition of TBK-1 in mice with diet-induced obesity impaired glucose metabolism and AKT activation. Altogether, our data show a TBK-1-dependent role for central Lin28a in glucose homeostasis. © 2017 by the American Diabetes Association.

  17. A Tisket, A Tasket--Out of the Editor's Basket

    NASA Astrophysics Data System (ADS)

    Williams, Kathryn R.

    2001-05-01

    In September 1940, the Journal introduced Out of the Editor's Basket for short items of interest: excerpts from letters, pamphlets, newspapers, and periodicals. By 1950, however, the Editor's Basket had evolved into a bulletin board for descriptions of new products and services, and it now contains almost exclusively press releases about recently marketed items. Now over 60 years old, the Editor's Basket still provides interesting tidbits for the Journal's broad readership.

  18. From the Board of Editors: on Plagiarism

    NASA Astrophysics Data System (ADS)

    2005-05-01

    Dear Colleagues: There has been a significant increase in the number of duplicate submissions and plagiarism cases reported in all major journals, including the journals of the Optical Society of America. Duplicate submissions and plagiarism can take many forms, and all of them are violations of professional ethics, the copyright agreement that an author signs along with the submission of a paper, and OSA's published Author Guidelines. There must be a significant component of new science for a paper to be publishable. The copying of large segments of text from previously published or in-press papers with only minor cosmetic changes is not acceptable and can lead to the rejection of papers. Duplicate submission: Duplicate submission is the most common ethics violation encountered. Duplicate submission is the submission of substantially similar papers to more than one journal. There is a misperception in a small fraction of the scientific community that duplicate submission is acceptable because it sometimes takes a long time to get a paper reviewed and because one of the papers can be withdrawn at any time. This is a clear violation of professional ethics and of the copyright agreement that is signed on submission. Duplicate submission harms the whole community because editors and reviewers waste their time and in the process compound the time it takes to get a paper reviewed for all authors. In cases of duplicate submission, the Editor of the affected OSA journal will consult with the Editor of the other journal involved to determine the proper course of action. Often that action will be the rejection of both papers. Plagiarism: Plagiarism is a serious breach of ethics and is defined as the substantial replication, without attribution, of significant elements of another document already published by the same or other authors. Two types of plagiarism can occur-self-plagiarism and plagiarism from others' works. Self-plagiarism is the publication of substantially

  19. From the Board of Editors: on Plagiarism

    NASA Astrophysics Data System (ADS)

    2005-04-01

    Dear Colleagues: There has been a significant increase in the number of duplicate submissions and plagiarism cases reported in all major journals, including the journals of the Optical Society of America. Duplicate submissions and plagiarism can take many forms, and all of them are violations of professional ethics, the copyright agreement that an author signs along with the submission of a paper, and OSA's published Author Guidelines. There must be a significant component of new science for a paper to be publishable. The copying of large segments of text from previously published or in-press papers with only minor cosmetic changes is not acceptable and can lead to the rejection of papers. Duplicate submission: Duplicate submission is the most common ethics violation encountered. Duplicate submission is the submission of substantially similar papers to more than one journal. There is a misperception in a small fraction of the scientific community that duplicate submission is acceptable because it sometimes takes a long time to get a paper reviewed and because one of the papers can be withdrawn at any time. This is a clear violation of professional ethics and of the copyright agreement that is signed on submission. Duplicate submission harms the whole community because editors and reviewers waste their time and in the process compound the time it takes to get a paper reviewed for all authors. In cases of duplicate submission, the Editor of the affected OSA journal will consult with the Editor of the other journal involved to determine the proper course of action. Often that action will be the rejection of both papers. Plagiarism: Plagiarism is a serious breach of ethics and is defined as the substantial replication, without attribution, of significant elements of another document already published by the same or other authors. Two types of plagiarism can occur-self-plagiarism and plagiarism from others' works. Self-plagiarism is the publication of substantially

  20. EDITORIAL: Incoming Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Lidström, Suzanne

    2012-04-01

    When Professor Anders Bárány took over as the Executive Editor of Physica Scripta, in 1986, he talked of his trepidation at having to 'dress himself' in his predecessor's 'editorial coveralls'. At that time, they had been worn by Professor Nils Robert Nilsson, a major figure in the physics community, for almost 20 years. Just one year prior to this, Professor Roger Wäppling had been recruited to the position of Subeditor in conjunction with a decision to expand the number of contributions in the field of condensed matter physics, to turn it into one of the dominant subjects in the broad-based journal. Physica Scripta had already gained a reputation for being a high quality journal with wide coverage of both experimental and theoretical physics. Interestingly, in the mid 1980s, the number of papers submitted had been growing and an impressive 250 submissions per year had been attained, with all of the manuscripts being handled in-house. Not many miles away in the town of Uppsala, a group of English students was stepping off a train on a magnificent snowy day in January to embark on their final year projects. A couple of us enjoyed ourselves so much that we stayed on afterwards as PhD students, thereby encountering the mixed pleasure of studying physics in a second language for the first time. I used to copy the notes down meticulously in Swedish, then try to work backwards with a textbook to improve my language skills. One day, returning from a particularly incomprehensible lecture on solid state physics, I showed my roommates my notes and asked if they could please explain what the lecture had been about: 'I don't know', they replied, 'but this bit is about sheep!' Meanwhile, back at Physica Scripta, the journal continued to flourish: 400 submissions were received in 1996, and the march of progress was well underway. Manuscripts could now be sent in on disks and Physica Scripta was available on the World Wide Web. Roger was appointed to manage the journal and

  1. A Dynamic Attitude Measurement System Based on LINS

    PubMed Central

    Li, Hanzhou; Pan, Quan; Wang, Xiaoxu; Zhang, Juanni; Li, Jiang; Jiang, Xiangjun

    2014-01-01

    A dynamic attitude measurement system (DAMS) is developed based on a laser inertial navigation system (LINS). Three factors of the dynamic attitude measurement error using LINS are analyzed: dynamic error, time synchronization and phase lag. An optimal coning errors compensation algorithm is used to reduce coning errors, and two-axis wobbling verification experiments are presented in the paper. The tests indicate that the attitude accuracy is improved 2-fold by the algorithm. In order to decrease coning errors further, the attitude updating frequency is improved from 200 Hz to 2000 Hz. At the same time, a novel finite impulse response (FIR) filter with three notches is designed to filter the dither frequency of the ring laser gyro (RLG). The comparison tests suggest that the new filter is five times more effective than the old one. The paper indicates that phase-frequency characteristics of FIR filter and first-order holder of navigation computer constitute the main sources of phase lag in LINS. A formula to calculate the LINS attitude phase lag is introduced in the paper. The expressions of dynamic attitude errors induced by phase lag are derived. The paper proposes a novel synchronization mechanism that is able to simultaneously solve the problems of dynamic test synchronization and phase compensation. A single-axis turntable and a laser interferometer are applied to verify the synchronization mechanism. The experiments results show that the theoretically calculated values of phase lag and attitude error induced by phase lag can both match perfectly with testing data. The block diagram of DAMS and physical photos are presented in the paper. The final experiments demonstrate that the real-time attitude measurement accuracy of DAMS can reach up to 20″ (1σ) and the synchronization error is less than 0.2 ms on the condition of three axes wobbling for 10 min. PMID:25177802

  2. Lin28 Enhances Tumorigenesis and is Associated With Advanced Human Malignancies

    PubMed Central

    Viswanathan, Srinivas R.; Powers, John T.; Einhorn, William; Hoshida, Yujin; Ng, Tony; Toffanin, Sara; O'Sullivan, Maureen; Lu, Jun; Philips, Letha A.; Lockhart, Victoria L.; Shah, Samar P.; Tanwar, Pradeep S.; Mermel, Craig H.; Beroukhim, Rameen; Azam, Mohammad; Teixeira, Jose; Meyerson, Matthew; Hughes, Timothy P.; Llovet, Josep M; Radich, Jerald; Mullighan, Charles G.; Golub, Todd R.; Sorensen, Poul H.; Daley, George Q.

    2009-01-01

    Multiple members of the let-7 family of miRNAs are often repressed in human cancers1,2, thereby promoting oncogenesis by de-repressing the targets K-Ras, c-Myc, and HMGA2 3,4. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins Lin28 and Lin28B block let-7 precursors from being processed to mature miRNAs5–8, suggesting that over-expression of Lin28/Lin28B might promote malignancy via repression of let-7. Here we show that LIN28 and LIN28B are over-expressed in primary human tumors and human cancer cell lines (overall frequency ∼15%), and that over-expression is linked to repression of let-7 family miRNAs and de-repression of let-7 targets. Lin28/Lin28B facilitate cellular transformation in vitro, and over-expression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28/LIN28B with poor clinical prognosis. PMID:19483683

  3. Lin-28 promotes symmetric stem cell division and drives adaptive growth in the adult Drosophila intestine.

    PubMed

    Chen, Ching-Huan; Luhur, Arthur; Sokol, Nicholas

    2015-10-15

    Stem cells switch between asymmetric and symmetric division to expand in number as tissues grow during development and in response to environmental changes. The stem cell intrinsic proteins controlling this switch are largely unknown, but one candidate is the Lin-28 pluripotency factor. A conserved RNA-binding protein that is downregulated in most animals as they develop from embryos to adults, Lin-28 persists in populations of adult stem cells. Its function in these cells has not been previously characterized. Here, we report that Lin-28 is highly enriched in adult intestinal stem cells in the Drosophila intestine. lin-28 null mutants are homozygous viable but display defects in this population of cells, which fail to undergo a characteristic food-triggered expansion in number and have reduced rates of symmetric division as well as reduced insulin signaling. Immunoprecipitation of Lin-28-bound mRNAs identified Insulin-like Receptor (InR), forced expression of which completely rescues lin-28-associated defects in intestinal stem cell number and division pattern. Furthermore, this stem cell activity of lin-28 is independent of one well-known lin-28 target, the microRNA let-7, which has limited expression in the intestinal epithelium. These results identify Lin-28 as a stem cell intrinsic factor that boosts insulin signaling in intestinal progenitor cells and promotes their symmetric division in response to nutrients, defining a mechanism through which Lin-28 controls the adult stem cell division patterns that underlie tissue homeostasis and regeneration.

  4. Role of LIN28A in mouse and human trophoblast cell differentiation.

    PubMed

    Seabrook, Jill L; Cantlon, Jeremy D; Cooney, Austin J; McWhorter, Erin E; Fromme, Brittany A; Bouma, Gerrit J; Anthony, Russell V; Winger, Quinton A

    2013-10-01

    Proper regulation of trophoblast proliferation, differentiation, and function are critical for placenta development and function. The RNA-binding protein, LIN28A, has been well characterized as a potent regulator of differentiation in embryonic stem cells; however, little is known about the function of LIN28A in the placenta. We assessed LIN28A in vitro using mouse trophoblast stem (mTS) cells and human trophoblast cells (ACH-3P). We observed that LIN28A decreased and let-7 miRNA increased when mTS cells were induced to differentiate into mouse trophoblast giant cells (mTGCs) upon the removal of FGF4, heparin and conditioned medium. Similarly, we observed that LIN28A decreased in ACH-3P cells induced to syncytialize with forskolin treatment. To assess LIN28A in vivo we examined Embryonic Day 11.5 mouse placenta and observed abundant LIN28A in the chorioallantoic interface and labyrinth layer, with little LIN28A staining in spongiotrophoblast or differentiated mTGCs. Additionally, shRNA-mediated LIN28A knockdown in ACH-3P cells resulted in increased spontaneous syncytialization, and increased levels of syncytiotrophoblast markers hCG, LGALS13, and ERVW-1 mRNA. Additionally, targeted degradation of LIN28A mRNA increased responsiveness to forskolin-induced differentiation. In contrast, targeted degradation of Lin28a mRNA in mTS cells did not alter cell phenotype when maintained under proliferative culture conditions. Together, these data establish that LIN28A has a functional role in regulating trophoblast differentiation and function, and that loss of LIN28A in human trophoblast is sufficient to induce differentiation, but does not induce differentiation in the mouse.

  5. Role of LIN28A in Mouse and Human Trophoblast Cell Differentiation1

    PubMed Central

    Seabrook, Jill L.; Cantlon, Jeremy D.; Cooney, Austin J.; McWhorter, Erin E.; Fromme, Brittany A.; Bouma, Gerrit J.; Anthony, Russell V.; Winger, Quinton A.

    2013-01-01

    ABSTRACT Proper regulation of trophoblast proliferation, differentiation, and function are critical for placenta development and function. The RNA-binding protein, LIN28A, has been well characterized as a potent regulator of differentiation in embryonic stem cells; however, little is known about the function of LIN28A in the placenta. We assessed LIN28A in vitro using mouse trophoblast stem (mTS) cells and human trophoblast cells (ACH-3P). We observed that LIN28A decreased and let-7 miRNA increased when mTS cells were induced to differentiate into mouse trophoblast giant cells (mTGCs) upon the removal of FGF4, heparin and conditioned medium. Similarly, we observed that LIN28A decreased in ACH-3P cells induced to syncytialize with forskolin treatment. To assess LIN28A in vivo we examined Embryonic Day 11.5 mouse placenta and observed abundant LIN28A in the chorioallantoic interface and labyrinth layer, with little LIN28A staining in spongiotrophoblast or differentiated mTGCs. Additionally, shRNA-mediated LIN28A knockdown in ACH-3P cells resulted in increased spontaneous syncytialization, and increased levels of syncytiotrophoblast markers hCG, LGALS13, and ERVW-1 mRNA. Additionally, targeted degradation of LIN28A mRNA increased responsiveness to forskolin-induced differentiation. In contrast, targeted degradation of Lin28a mRNA in mTS cells did not alter cell phenotype when maintained under proliferative culture conditions. Together, these data establish that LIN28A has a functional role in regulating trophoblast differentiation and function, and that loss of LIN28A in human trophoblast is sufficient to induce differentiation, but does not induce differentiation in the mouse. PMID:24006280

  6. High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer.

    PubMed

    Hamano, R; Miyata, H; Yamasaki, M; Sugimura, K; Tanaka, K; Kurokawa, Y; Nakajima, K; Takiguchi, S; Fujiwara, Y; Mori, M; Doki, Y

    2012-04-10

    Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not been elucidated. Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line. Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells. High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.

  7. John F. Dewey—Tectonics Editor

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    ‘I want the journal to acquire a reputation for very rapid, fair, and accurate reviewing,’ asserted John F. Dewey, editor-in-chief of AGU's newest journal, Tectonics. Dewey said that he will rule the bimonthly, which will begin publication in February, ‘with a bit of a rod of iron’ to ensure that Tectonics is ‘where only original and important papers are published.’‘I'm going to be very strict with reviewers,’ Dewey explained in his quick British clip. ‘If the review does not come back to me within 10 days to 2 weeks, I'll review the paper myself. I'm also going to have a system whereby, if a paper needs major surgery after being refereed, it will be rejected. Papers will have to be in virtually publishable condition before they are first submitted,’ he said.

  8. A former Editor views the editorial process

    NASA Astrophysics Data System (ADS)

    Freeze, R. Allan

    It was at the AGU Fall Meeting in San Francisco in December 1976, shortly after my appointment as coeditor of Water Resources Research that I first began to realize the strong emotional ties that exist between a scientific community and its journals. Feelings run high, regardless of whether they come from readers, contributors, reviewers, active scientists, or scientific administrators. Opinions are often positive, sometimes negative, usually a mixture of the two; but regardless of their tenor they are delivered to the editor, in person, usually fortissimo. From that day until this, conference life has never been dull. When I meet a colleague in the halls there is never a loss for words, no need to search for a topic of mutual interest; WRR is always there at the ready.

  9. Generating the Field: The Role of Editors in Disciplinary Formation

    ERIC Educational Resources Information Center

    Selfe, Cynthia; Villanueva, Victor; Parks, Steve

    2017-01-01

    In the following conversation, conducted asynchronously through email, three current and former editors discuss the role of publishing in creating a disciplinary identity. Speaking from the academic (Villanueva), digital (Selfe), and community (Parks), and, often crossing these three categories, the editors discuss how the field has failed to…

  10. Journal Editor Perceptions of Universities: Some Empirical Evidence

    ERIC Educational Resources Information Center

    Mainardes, Emerson Wagner; Raposo, Mario; Alves, Helena

    2012-01-01

    Out of considerations as to the importance of university relationships with their various stakeholders, the primary objective of this research project was to identify the perceptions of academic journal editors regarding universities. Editors were asked to provide their perceptions on: (a) the relevance of universities to academic publications;…

  11. Peer reviews and the role of a journal editor

    USDA-ARS?s Scientific Manuscript database

    Obtaining peer reviews for manuscripts submitted to scientific journals is becoming increasingly difficult. Changes to the system are necessary, and editors must cultivate and maintain a solid base of reviewers to help evaluate journal submissions. This article outlines some steps editors can and sh...

  12. A graphic editor for analyzing signal-transduction pathways.

    PubMed

    Koike, T; Rzhetsky, A

    2000-12-23

    We describe a graphical editor designed specifically to facilitate analysis and visualization of complex signal-transduction pathways. The editor provides automatic layout of complex regulatory graphs and enables users easily to maintain, edit, and exchange publication-quality images of regulatory networks.

  13. The RAE and Publications: A Review of Journal Editors.

    ERIC Educational Resources Information Center

    Talib, Ameen Ali

    2000-01-01

    Surveyed editors of academic journals about publication issues related to Britain's Research Assessment Exercise (RAE), a process of grading and funding universities based on published research output. Editors were asked about research quality and output, publication practices, academics' willingness to referee manuscripts, and proliferation of…

  14. How Newspaper Editors Reacted to "Post's" Pulitzer Prize Hoax.

    ERIC Educational Resources Information Center

    Anderson, Douglas A.

    1982-01-01

    Reports the findings of a nationwide survey of newspaper editors, revealing that most thought that the Janet Cooke hoax had been poorly handled by the "Washington Post." Notes that most of the editors said their newspapers had systems of review for stories coming from anonymous sources. (FL)

  15. The RAE and Publications: A Review of Journal Editors.

    ERIC Educational Resources Information Center

    Talib, Ameen Ali

    2000-01-01

    Surveyed editors of academic journals about publication issues related to Britain's Research Assessment Exercise (RAE), a process of grading and funding universities based on published research output. Editors were asked about research quality and output, publication practices, academics' willingness to referee manuscripts, and proliferation of…

  16. March 2017 Letters to the Editor-in-Chief.

    PubMed

    2017-03-01

    Letters to the Editor-in-Chief of JOSPT as follows: "Regarding 'Unraveling the Complexity of Low Back Pain'" with Authors' Response "Beall's List Has Vanished: What Next?" with Editor-in-Chief Response J Orthop Sports Phys Ther 2017;47(3):219-223. doi:10.2519/jospt.2017.0202.

  17. JSME: a free molecule editor in JavaScript.

    PubMed

    Bienfait, Bruno; Ertl, Peter

    2013-01-01

    A molecule editor, i.e. a program facilitating graphical input and interactive editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. Today, when a web browser has become the universal scientific user interface, a tool to edit molecules directly within the web browser is essential. One of the most popular tools for molecular structure input on the web is the JME applet. Since its release nearly 15 years ago, however the web environment has changed and Java applets are facing increasing implementation hurdles due to their maintenance and support requirements, as well as security issues. This prompted us to update the JME editor and port it to a modern Internet programming language - JavaScript. The actual molecule editing Java code of the JME editor was translated into JavaScript with help of the Google Web Toolkit compiler and a custom library that emulates a subset of the GUI features of the Java runtime environment. In this process, the editor was enhanced by additional functionalities including a substituent menu, copy/paste, drag and drop and undo/redo capabilities and an integrated help. In addition to desktop computers, the editor supports molecule editing on touch devices, including iPhone, iPad and Android phones and tablets. In analogy to JME the new editor is named JSME. This new molecule editor is compact, easy to use and easy to incorporate into web pages. A free molecule editor written in JavaScript was developed and is released under the terms of permissive BSD license. The editor is compatible with JME, has practically the same user interface as well as the web application programming interface. The JSME editor is available for download from the project web page http://peter-ertl.com/jsme/

  18. JSME: a free molecule editor in JavaScript

    PubMed Central

    2013-01-01

    Background A molecule editor, i.e. a program facilitating graphical input and interactive editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. Today, when a web browser has become the universal scientific user interface, a tool to edit molecules directly within the web browser is essential. One of the most popular tools for molecular structure input on the web is the JME applet. Since its release nearly 15 years ago, however the web environment has changed and Java applets are facing increasing implementation hurdles due to their maintenance and support requirements, as well as security issues. This prompted us to update the JME editor and port it to a modern Internet programming language - JavaScript. Summary The actual molecule editing Java code of the JME editor was translated into JavaScript with help of the Google Web Toolkit compiler and a custom library that emulates a subset of the GUI features of the Java runtime environment. In this process, the editor was enhanced by additional functionalities including a substituent menu, copy/paste, drag and drop and undo/redo capabilities and an integrated help. In addition to desktop computers, the editor supports molecule editing on touch devices, including iPhone, iPad and Android phones and tablets. In analogy to JME the new editor is named JSME. This new molecule editor is compact, easy to use and easy to incorporate into web pages. Conclusions A free molecule editor written in JavaScript was developed and is released under the terms of permissive BSD license. The editor is compatible with JME, has practically the same user interface as well as the web application programming interface. The JSME editor is available for download from the project web page http://peter-ertl.com/jsme/ PMID:23694746

  19. Representation of women as editors in the Cochrane collaboration.

    PubMed

    Bhaumik, Soumyadeep; Mathew, Rebecca Joyce

    2014-12-01

    There is considerable gender disparity in editorial boards of medical journals. Being an editor in a Cochrane review group (CRG), like being an editor in a medical journal, is an indirect representation of one's reputation and leadership abilities in a particular specialty. The aim of the study was to analyze the representation of women editors on the editorial teams of CRG's and the Central Editorial Unit (CEU) of the Cochrane Collaboration. Information about editorial team members of CRGs and the CEU was extracted from respective websites. Gender of the individual was determined by inspection of names, individual profile description or photographs in the CRG or institutional webpage, social networking sites and internet search. Data was validated by two authors independently and differences sorted by consensus. A total of 788 editors across all CRGs and the CEU with an overall 371 females (47.1%) and 417 (52.9%) males were identified. of the CEU editors, 62.5% were females. There were 68 coordinating editors (35.3% females), and 62 managing editors (56% females), who provided leadership to the CRGs. Eighty-four percent of trial search coordinators were found to be females. Ten CRGs had 75% or more of its editors as females while 7 CRGs had less than or equal to 25% female editors. The representation of women editors in the Cochrane Collaboration was found to be better than in editorial boards of medical journals. There is still scope for improvement to ensure better gender diversity across all roles and in all CRG's. © 2014 Chinese Cochrane Center, West China Hospital of Sichuan University and Wiley Publishing Asia Pty Ltd.

  20. Expression of LIN28 and its regulatory microRNAs in adult adrenocortical cancer.

    PubMed

    Faria, André M; Sbiera, Silviu; Ribeiro, Tamaya C; Soares, Iberê C; Mariani, Beatriz M P; Freire, Daniel S; de Sousa, Gabriela R V; Lerario, Antônio M; Ronchi, Cristina L; Deutschbein, Timo; Wakamatsu, Alda; Alves, Venancio A F; Zerbini, Maria Claudia N; Mendonca, Berenice B; Fragoso, Maria Candida B V; Latronico, Ana Claudia; Fassnacht, Martin; Almeida, Madson Q

    2015-04-01

    LIN28 control cells reprogramming and pluripotency mainly through miRNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN28 and its regulatory miRNAs in a large cohort of adrenocortical tumours (ACTs). LIN28 protein expression was assessed in 266 adults ACTs (78 adenomas and 188 carcinomas) from Brazil and Germany. LIN28A and LIN28B gene expression was analysed in 59 ACTs (31 adenomas and 28 carcinomas) and copy number variation in 39 ACTs. In addition, we determined the expression of let-7 family, mir-9, mir-30 and mir-125 in 28 carcinomas. LIN28A gene was overexpressed in aggressive ACCs when compared with adenomas and nonaggressive ACCs, but no LIN28A copy number variation was found in ACTs. Unexpectedly, weak LIN28 protein expression was significantly associated with reduced disease-free survival in ACC patients (P = 0·01), but for overall survival only a trend was detectable (P = 0·117). In the multivariate analysis, only Ki67 index ≥10% (HR 4·6, P = 0·000) and weak LIN28 protein expression (HR 2·0, P = 0·03) were independent predictors of recurrence in ACC patients. Interestingly, mir-9 expression, a negative LIN28A/B regulator, was significantly higher in aggressive than in nonaggressive ACCs [2076 (from 36 to 9307) vs 133·4 (from 2·4 to 5193); P = 0·011] and was highly associated with reduced overall (P = 0·01) and disease-free survival (P = 0·01). However, mir-9 prognostic role should be further evaluated in a larger cohort. Weak LIN28 protein expression was associated with recurrence in ACCs. Additionally, overexpression of mir-9, a negative LIN28A regulator, was associated with poor outcome. © 2014 John Wiley & Sons Ltd.

  1. Lin28a is dormant, functional, and dispensable during mouse oocyte-to-embryo transition.

    PubMed

    Flemr, Matyas; Moravec, Martin; Libova, Veronika; Sedlacek, Radislav; Svoboda, Petr

    2014-06-01

    The oocyte-to-embryo transition (OET) denotes transformation of a highly differentiated oocyte into totipotent blastomeres of the early mammalian embryo. OET depends exclusively on maternal RNAs and proteins accumulated during oocyte growth, which implies importance of post-transcriptional control of gene expression. OET includes replacement of abundant maternal microRNAs (miRNAs), enriched also in differentiated cells and exemplified by the Let-7 family, with embryonic miRNAs common in pluripotent stem cells (the miR-290 family in the mouse). Lin28a and its homolog Lin28b encode RNA-binding proteins, which interfere with Let-7 maturation and facilitate reprogramming of induced pluripotent stem cells. Both Lin28a and Lin28b transcripts are abundant in mouse oocytes. To test the role of maternal expression of Lin28a and Lin28b during oocyte-to-zygote reprogramming, we generated mice with oocyte-specific knockdown of both genes by using transgenic RNA interference. Lin28a and Lin28b are dispensable during oocyte growth because their knockdown has no effect on Let-7a levels in fully grown germinal vesicle (GV)-intact oocytes. Furthermore, transgenic females were fertile and produced healthy offspring, and their overall breeding performance was comparable to that of wild-type mice. At the same time, 2-cell embryos derived from transgenic females showed up-regulation of mature Let-7, suggesting that maternally provided LIN28A and LIN28B function during zygotic genome activation. Consistent with this conclusion is increased translation of Lin28a transcripts upon resumption of meiosis. Our data imply dual repression of Let-7 during OET in the mouse model, the selective suppression of Let-7 biogenesis by Lin28 homologs superimposed on previously reported global suppression of miRNA activity. © 2014 by the Society for the Study of Reproduction, Inc.

  2. Lin28 promotes growth of prostate cancer cells and activates the androgen receptor.

    PubMed

    Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Zhu, Yezi; Gandour-Edwards, Regina; Chen, Hong-Wu; Evans, Christopher P; Gao, Allen C

    2013-07-01

    Prostate cancer (CaP) progresses to a castration-resistant state assisted by multifold molecular changes, most of which involve activation of the androgen receptor (AR). Having previously demonstrated the importance of the Lin28/let-7/Myc axis in CaP, we tested the hypothesis that Lin28 is overexpressed in CaP and that it activates AR and promotes growth of CaP cells. We analyzed human clinical CaP samples for the expression of Lin28 by quantitative real-time RT-PCR, Western blot analysis, and IHC. Growth characteristics of CaP cell lines transiently and stably expressing Lin28 were examined. The clonogenic ability of CaP cells expressing Lin28 was determined by colony formation and soft agar assays. Increase in expression of AR and subsequent increase in transcription of AR-target genes were analyzed by quantitative real-time RT-PCR, luciferase assays, and ELISA. LNCaP cells stably expressing Lin28 were injected into nude mice, and tumorigenesis was monitored. We found that Lin28 is overexpressed in clinical CaP compared to benign prostates. Overexpression of Lin28 enhanced, while down-regulation reduced, growth of CaP cells. Lin28 enhanced the ability of CaP cells to form colonies in anchorage-dependent and anchorage-independent conditions. LNCaP cells stably expressing Lin28 exhibited significantly higher tumorigenic ability in vivo. Lin28 induced expression of the AR and its target genes such as PSA and NKX3.1. Collectively, our findings demonstrate a novel role for Lin28 in CaP development and activation of the AR axis. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Lin28 Promotes Growth of Prostate Cancer Cells and Activates the Androgen Receptor

    PubMed Central

    Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Zhu, Yezi; Gandour-Edwards, Regina; Chen, Hong-Wu; Evans, Christopher P.; Gao, Allen C.

    2014-01-01

    Prostate cancer (CaP) progresses to a castration-resistant state assisted by multifold molecular changes, most of which involve activation of the androgen receptor (AR). Having previously demonstrated the importance of the Lin28/let-7/Myc axis in CaP, we tested the hypothesis that Lin28 is overexpressed in CaP and that it activates AR and promotes growth of CaP cells. We analyzed human clinical CaP samples for the expression of Lin28 by quantitative real-time RT-PCR, Western blot analysis, and IHC. Growth characteristics of CaP cell lines transiently and stably expressing Lin28 were examined. The clonogenic ability of CaP cells expressing Lin28 was determined by colony formation and soft agar assays. Increase in expression of AR and subsequent increase in transcription of AR-target genes were analyzed by quantitative real-time RT-PCR, luciferase assays, and ELISA. LNCaP cells stably expressing Lin28 were injected into nude mice, and tumorigenesis was monitored. We found that Lin28 is overexpressed in clinical CaP compared to benign prostates. Overexpression of Lin28 enhanced, while down-regulation reduced, growth of CaP cells. Lin28 enhanced the ability of CaP cells to form colonies in anchorage-dependent and anchorage-independent conditions. LNCaP cells stably expressing Lin28 exhibited significantly higher tumorigenic ability in vivo. Lin28 induced expression of the AR and its target genes such as PSA and NKX3.1. Collectively, our findings demonstrate a novel role for Lin28 in CaP development and activation of the AR axis. PMID:23790802

  4. A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans

    PubMed Central

    Polley, Stanley R. G.; Fay, David S.

    2012-01-01

    The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified in genetic screens for mutations that display synthetic phenotypes in conjunction with loss of lin-35. To explore the intestinal role of LIN-35, we conducted a genome-wide RNA-interference-feeding screen for suppressors of lin-35; slr-2 early larval arrest. Of the 26 suppressors identified, 17 fall into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators. Further characterization indicates that different categories of suppressors act through distinct molecular mechanisms. We also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes. We identified 19 genes, most of which are evolutionarily conserved, that can suppress multiple unrelated lin-35-synthetic phenotypes. Our study reveals a network of genes broadly antagonistic to LIN-35 as well as genes specific to the role of LIN-35 in intestinal and vulval development. Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities are most directly relevant to the core functions of the shared gene. PMID:22542970

  5. lin-28 controls the succession of cell fate choices via two distinct activities.

    PubMed

    Vadla, Bhaskar; Kemper, Kevin; Alaimo, Jennifer; Heine, Christian; Moss, Eric G

    2012-01-01

    lin-28 is a conserved regulator of cell fate succession in animals. In Caenorhabditis elegans, it is a component of the heterochronic gene pathway that governs larval developmental timing, while its vertebrate homologs promote pluripotency and control differentiation in diverse tissues. The RNA binding protein encoded by lin-28 can directly inhibit let-7 microRNA processing by a novel mechanism that is conserved from worms to humans. We found that C. elegans LIN-28 protein can interact with four distinct let-7 family pre-microRNAs, but in vivo inhibits the premature accumulation of only let-7. Surprisingly, however, lin-28 does not require let-7 or its relatives for its characteristic promotion of second larval stage cell fates. In other words, we find that the premature accumulation of mature let-7 does not account for lin-28's precocious phenotype. To explain let-7's role in lin-28 activity, we provide evidence that lin-28 acts in two steps: first, the let-7-independent positive regulation of hbl-1 through its 3'UTR to control L2 stage-specific cell fates; and second, a let-7-dependent step that controls subsequent fates via repression of lin-41. Our evidence also indicates that let-7 functions one stage earlier in C. elegans development than previously thought. Importantly, lin-28's two-step mechanism resembles that of the heterochronic gene lin-14, and the overlap of their activities suggests a clockwork mechanism for developmental timing. Furthermore, this model explains the previous observation that mammalian Lin28 has two genetically separable activities. Thus, lin-28's two-step mechanism may be an essential feature of its evolutionarily conserved role in cell fate succession.

  6. Academic Degradation and the Retreat of the Editors: Academic Irregularities and the Spreading of Academic Corruption from an Editor's Perspective

    ERIC Educational Resources Information Center

    Xun, Gong

    2007-01-01

    Against the backdrop of the grave academic crisis in China, editors have become the objects of wooing, favor-currying, connections-seeking, and collusions; they have been targeted for attacks, plots, extortions, and encroachments. Editing and publishing have become avenues for academic irregularities and academic corruption. Editors have the power…

  7. Academic Degradation and the Retreat of the Editors: Academic Irregularities and the Spreading of Academic Corruption from an Editor's Perspective

    ERIC Educational Resources Information Center

    Xun, Gong

    2007-01-01

    Against the backdrop of the grave academic crisis in China, editors have become the objects of wooing, favor-currying, connections-seeking, and collusions; they have been targeted for attacks, plots, extortions, and encroachments. Editing and publishing have become avenues for academic irregularities and academic corruption. Editors have the power…

  8. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models.

    PubMed

    Nguyen, Liem H; Robinton, Daisy A; Seligson, Marc T; Wu, Linwei; Li, Lin; Rakheja, Dinesh; Comerford, Sarah A; Ramezani, Saleh; Sun, Xiankai; Parikh, Monisha S; Yang, Erin H; Powers, John T; Shinoda, Gen; Shah, Samar P; Hammer, Robert E; Daley, George Q; Zhu, Hao

    2014-08-11

    Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans.

    PubMed

    Tu, Ho-Chou; Schwitalla, Sarah; Qian, Zhirong; LaPier, Grace S; Yermalovich, Alena; Ku, Yuan-Chieh; Chen, Shann-Ching; Viswanathan, Srinivas R; Zhu, Hao; Nishihara, Reiko; Inamura, Kentaro; Kim, Sun A; Morikawa, Teppei; Mima, Kosuke; Sukawa, Yasutaka; Yang, Juhong; Meredith, Gavin; Fuchs, Charles S; Ogino, Shuji; Daley, George Q

    2015-05-15

    Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in Apc(Min/+) mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target. © 2015 Tu et al.; Published by Cold Spring Harbor Laboratory Press.

  10. LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

    PubMed Central

    Tu, Ho-Chou; Schwitalla, Sarah; Qian, Zhirong; LaPier, Grace S.; Yermalovich, Alena; Ku, Yuan-Chieh; Chen, Shann-Ching; Viswanathan, Srinivas R.; Zhu, Hao; Nishihara, Reiko; Inamura, Kentaro; Kim, Sun A.; Morikawa, Teppei; Mima, Kosuke; Sukawa, Yasutaka; Yang, Juhong; Meredith, Gavin; Fuchs, Charles S.; Ogino, Shuji

    2015-01-01

    Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in ApcMin/+ mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target. PMID:25956904

  11. Martin Stutzmann: Editor, Teacher, Scientist and Friend

    NASA Astrophysics Data System (ADS)

    Cardona, Manuel

    2005-03-01

    On 2 January 1995 Martin Stutzmann became Editor-in-Chief of physica status solidi, replacing Professor E. Gutsche, who had led the journal through the stormy period involving the fall of the Iron Curtain, the unification of Germany and the change in its Eastern part, where physica status solidi was based, from socialism as found in the real world (a German concept) to real world capitalism. In 1995 it was thought that the process had been completed (we should have known better!) and after the retirement of Prof. Gutsche the new owners of physica status solidi (Wiley-VCH) decided that a change in scientific management was desirable to adapt to the new socio-political facts and to insure the scientific continuity of the journal.Martin had moved in 1993 from my department at the Max-Planck-Institute to Munich where he soon displayed a tremendous amount of science man- agement ability during the build-up of the Walter Schottky Institute. The search for a successor as Edi- tor-in-Chief was not easy: the job was not very glamorous after the upheavals which had taken place in the editorial world following the political changes. Somebody in the Editorial Boards must have suggested Martin Stutzmann. I am sure that there was opposition: one usually looks for a well-established person ready to leave his direct involvement in science and take up a new endeavor of a more administrative nature. Nevertheless, the powers that be soon realized that Martin was an excellent, if somewhat unconventional candidate who had enough energy to remain a topnotch scientist and to lead the journal in the difficult times ahead: he was offered the job. In the negotiations that followed, he insisted in getting the administrative structures that would allow him to improve the battered quality of the journal and to continue his scientific productivity. Today we are happy to see that he succeeded in both endeavors. The journal has since grown in size and considerably improved its quality

  12. A Rapid Induction Mechanism for Lin28a in Trophic Responses.

    PubMed

    Amen, Alexandra M; Ruiz-Garzon, Claudia R; Shi, Jay; Subramanian, Megha; Pham, Daniel L; Meffert, Mollie K

    2017-02-02

    Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophic stimuli to induce Lin28 have remained uncharacterized. We find that Lin28a protein exhibits rapid basal turnover in neurons and that mitogen-activated protein kinase (MAPK)-dependent phosphorylation of the RNA-silencing factor HIV TAR-RNA-binding protein (TRBP) promotes binding and stabilization of Lin28a, but not Lin28b, with an accompanying reduction in Lin28-regulated miRNAs, downstream of brain-derived neurotrophic factor (BDNF). Binding of Lin28a to TRBP in vitro is also enhanced by phospho-mimic TRBP. Further, phospho-TRBP recapitulates BDNF-induced neuronal dendritic spine growth in a Lin28a-dependent manner. Finally, we demonstrate MAPK-dependent TRBP and Lin28a induction, with physiological function in growth and survival, downstream of diverse growth factors in multiple primary cell types, supporting a broad role for this pathway in trophic responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Lin28A and androgen receptor expression in ER-/Her2+ breast cancer.

    PubMed

    Shen, Honghong; Yang, Yong; Zhao, Lin; Yuan, Jinyang; Niu, Yun

    2016-02-01

    The aim of this study was to examine the expression of Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, and to research the association of Lin28A and AR co-expression status with patients' prognosis. The expression of Lin28A and AR in formalin-fixed and paraffin-embedded surgical sections from 305 patients with ER-/Her2+ breast cancer was analyzed by immunohistochemistry, and the co-expression patterns in breast cancer cells were investigated by immunofluorescent staining. The impact of the expression of Lin28A and AR in prognosis was also assessed by the Kaplan-Meier, univariate, and multivariate logistic regression models. This study included 305 cases ER-/Her2+ breast cancer patients. Lin28A and AR were expressed in 240 cases (78.7 %) and 220 cases (72.1 %), respectively. Lin28A tended to be higher in AR-positive patients (75.0 %). Lin28A and AR co-expression (Lin28+/AR+) was significantly associated with high tumor grade (G3) (p = 0.023) and high Ki67 index (p = 0.020). The mRNA and protein expression levels of Lin28A and AR were higher in MDA-MB-453 cells (ER-/Her2+) than in the MDA-MB-231 cells (ER-/Her2-). In univariate analysis, Lin28A+/AR+ was significant risk factors associated with unfavorable OS (p = 0.049) and RFS (p = 0.019). Kaplan-Meier analysis showed that Lin28A+/AR+ expression showed lower RFS rates compared with Lin28A-/AR+ (p = 0.043) and Lin28A-/AR- patients(p = 0.019). Multivariate cox model showed that Lin28A+/AR+ remained an independent negative prognostic factor for RFS. Our study showed that Lin28A and AR co-expressed in ER-/Her-2+ breast cancer and correlated with poor prognosis. The possibility that Lin28A may drive AR expression via a positive feedback mechanism remains to be tested.

  14. Oncogenic mechanisms of Lin28 in breast cancer: new functions and therapeutic opportunities

    PubMed Central

    Seifer, Benjamin J.; Ye, Chenyang; Chen, Yongxia; Jia, Yunlu; Chen, Cong; Shen, Jianguo; Wang, Linbo; Sui, Xinbing; Zhou, Jichun

    2017-01-01

    The RNA binding protein Lin28 is best known for the critical role in cell development, recent researches also have implied its oncogenic function in various human cancers, including breast cancer. Specifically, aberrant Lin28 participates in multiple pathological processes, such as proliferation, metastasis, radiotherapy and chemotherapy resistance, metabolism, immunity and inflammation as well as stemness. In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer. PMID:28147339

  15. Positive expression of Lin28 is correlated with poor survival in gastric carcinoma.

    PubMed

    Xu, Chaoyang; Shen, Jiangguo; Xie, Shuduo; Jiang, Zhinong; Huang, Liming; Wang, Linbo

    2013-03-01

    The purpose of this study was to investigate the expression of Lin28 in gastric carcinoma and to assess its clinical significance. The expression level of Lin28 was assessed by reverse-transcriptase polymerase chain reaction in 10 surgically resected gastric carcinoma and corresponding normal tissues, and by immunohistochemical staining in surgically resected gastric carcinoma tissues of 229 patients, including 215 curative resection patients and 14 palliative resection patients. The expression level of Lin28 mRNA in gastric carcinoma tissues and corresponding normal tissues had no statistically significant difference. In curative resection patients, Lin28 protein expression was positive in 99 of 215 (46.0 %) gastric carcinoma tissues. In palliative resection patients, Lin28 protein expression was positive in 4 of 14 (28.6 %) gastric carcinoma tissues. In R0 patients, Lin28 protein positive expression was correlated with poor outcome (P = 0.017). In multivariate analysis, the Lin28 protein positive expression was a significant independent prognostic factor for overall survival (P = 0.024; HR, 1,768; 95 % CI 1.077-2.903). Our results indicate that Lin28 was expressed in both gastric carcinoma and corresponding normal tissues. Lin28 protein positive expression served as an independent prognostic factor.

  16. Oncogenic mechanisms of Lin28 in breast cancer: new functions and therapeutic opportunities.

    PubMed

    Xiong, Hanchu; Zhao, Wenhe; Wang, Ji; Seifer, Benjamin J; Ye, Chenyang; Chen, Yongxia; Jia, Yunlu; Chen, Cong; Shen, Jianguo; Wang, Linbo; Sui, Xinbing; Zhou, Jichun

    2017-04-11

    The RNA binding protein Lin28 is best known for the critical role in cell development, recent researches also have implied its oncogenic function in various human cancers, including breast cancer. Specifically, aberrant Lin28 participates in multiple pathological processes, such as proliferation, metastasis, radiotherapy and chemotherapy resistance, metabolism, immunity and inflammation as well as stemness. In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer.

  17. Reversible acetylation of Lin28 mediated by PCAF and SIRT1.

    PubMed

    Wang, Ling-xia; Wang, Jing; Qu, Ting-ting; Zhang, Ye; Shen, Yu-fei

    2014-06-01

    Lin28 is a small RNA-binding protein that plays an important role in regulating developmental timing, stem cell reprogramming, and oncogenesis. However, the significance of the effect of post-translational modifications on Lin28 activity is not fully understood. In this study, we demonstrated that PCAF directly interacted with and acetylated Lin28. We also showed that the acetylation of Lin28 can be specifically reversed by the deacetylase SIRT1. These findings suggest that the PCAF/SIRT1 balance plays an important role in regulating Lin28 activity. Furthermore, we found that the cold shock domain of Lin28 is the major target of PCAF-mediated acetylation, which leads to a severe reduction in the Lin28 protein levels and an increase in the level of mature let-7a. This study provides the first demonstration that post-translational modification regulates Lin28 activity during let-7a biogenesis and sheds light on the regulation of Lin28 in ES cells and carcinogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Targeting ornithine decarboxylase reverses the LIN28/Let-7 axis and inhibits glycolytic metabolism in neuroblastoma.

    PubMed

    Lozier, Ann M; Rich, Maria E; Grawe, Anissa Pedersen; Peck, Anderson S; Zhao, Ping; Chang, Anthony Ting-Tung; Bond, Jeffrey P; Sholler, Giselle Saulnier

    2015-01-01

    LIN28 has emerged as an oncogenic driver in a number of cancers, including neuroblastoma (NB). Overexpression of LIN28 correlates with poor outcome in NB, therefore drugs that impact the LIN28/Let-7 pathway could be beneficial in treating NB patients. The LIN28/Let-7 pathway affects many cellular processes including the regulation of cancer stem cells and glycolytic metabolism. Polyamines, regulated by ornithine decarboxylase (ODC) modulate eIF-5A which is a direct regulator of the LIN28/Let-7 axis. We propose that therapy inhibiting ODC will restore balance to the LIN28/Let-7 axis, suppress glycolytic metabolism, and decrease MYCN protein expression in NB. Difluoromethylornithine (DFMO) is an inhibitor of ODC in clinical trials for children with NB. In vitro experiments using NB cell lines, BE(2)-C, SMS-KCNR, and CHLA90 show that DFMO treatment reduced LIN28B and MYCN protein levels and increased Let-7 miRNA and decreased neurosphere formation. Glycolytic metabolic activity decreased with DFMO treatment in vivo. Additionally, sensitivity to DFMO treatment correlated with LIN28B overexpression (BE(2)-C>SMS-KCNR>CHLA90). This is the first study to demonstrate that DFMO treatment restores balance to the LIN28/Let-7 axis and inhibits glycolytic metabolism and neurosphere formation in NB and that PET scans may be a meaningful imaging tool to evaluate the therapeutic effects of DFMO treatment.

  19. The C. elegans developmental timing protein LIN-42 regulates diapause in response to environmental cues

    PubMed Central

    Tennessen, Jason M.; Opperman, Karla J.; Rougvie, Ann E.

    2010-01-01

    Environmental conditions can have a major impact on developmental progression in animals. For example, when C. elegans larvae encounter harsh conditions they can reversibly halt the passage of developmental time by forming a long-lived dauer larva at the end of the second larval stage. Here, we show that the period homolog lin-42, known to control developmental time, also acts as a component of a switch that mediates dauer entry. Loss of lin-42 function renders animals hypersensitive to dauer formation under stressful conditions, whereas misexpression of lin-42 in the pre-dauer stage inhibits dauer formation, indicating that lin-42 acts as a negative regulator of this life history decision. These phenotypes place LIN-42 in opposition to the ligand-free form of the nuclear receptor DAF-12, which indirectly senses environmental conditions and helps to integrate external cues into developmental decisions. Mutations that impair DAF-12 ligand binding are exquisitely sensitive to the absence of lin-42, whereas overexpression of LIN-42 can suppress the dauer constitutive phenotype of a ligand-insensitive daf-12 mutant, suggesting that LIN-42 and DAF-12 are intimate partners in controlling the decision to become a dauer larva. The functional outputs of Period family proteins and nuclear receptors also converge in other organisms, suggesting that the relationship between lin-42 and daf-12 represents an ancient genetic framework for responding to environmental stimuli. PMID:20843862

  20. LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance.

    PubMed

    Wilbert, Melissa L; Huelga, Stephanie C; Kapeli, Katannya; Stark, Thomas J; Liang, Tiffany Y; Chen, Stella X; Yan, Bernice Y; Nathanson, Jason L; Hutt, Kasey R; Lovci, Michael T; Kazan, Hilal; Vu, Anthony Q; Massirer, Katlin B; Morris, Quaid; Hoon, Shawn; Yeo, Gene W

    2012-10-26

    LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28-binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions.

  1. LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance

    PubMed Central

    Wilbert, Melissa L.; Huelga, Stephanie C.; Kapeli, Katannya; Stark, Thomas J.; Liang, Tiffany Y.; Chen, Stella X.; Yan, Bernice Y.; Nathanson, Jason L.; Hutt, Kasey R.; Lovci, Michael T.; Kazan, Hilal; Vu, Anthony Q; Massirer, Katlin B.; Morris, Quaid; Hoon, Shawn; Yeo, Gene W.

    2012-01-01

    SUMMARY LIN28 is a conserved RNA binding protein implicated in pluripotency, reprogramming and oncogenesis. Previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through cross-linking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28 binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions. PMID:22959275

  2. The C. elegans Chp/Wrch Ortholog CHW-1 Contributes to LIN-18/Ryk and LIN-17/Frizzled Signaling in Cell Polarity

    PubMed Central

    Kidd, Ambrose R.; Muñiz-Medina, Vanessa; Der, Channing J.; Cox, Adrienne D.; Reiner, David J.

    2015-01-01

    Wnt signaling controls various aspects of developmental and cell biology, as well as contributing to certain cancers. Expression of the human Rho family small GTPase Wrch/RhoU is regulated by Wnt signaling, and Wrch and its paralog Chp/RhoV are both implicated in oncogenic transformation and regulation of cytoskeletal dynamics. We performed developmental genetic analysis of the single Caenorhabditis elegans ortholog of Chp and Wrch, CHW-1. Using a transgenic assay of the distal tip cell migration, we found that wild-type CHW-1 is likely to be partially constitutively active and that we can alter ectopic CHW-1-dependent migration phenotypes with mutations predicted to increase or decrease intrinsic GTP hydrolysis rate. The vulval P7.p polarity decision balances multiple antagonistic Wnt signals, and also uses different types of Wnt signaling. Previously described cooperative Wnt receptors LIN-17/Frizzled and LIN-18/Ryk orient P7.p posteriorly, with LIN-17/Fz contributing approximately two-thirds of polarizing activity. CHW-1 deletion appears to equalize the contributions of these two receptors. We hypothesize that CHW-1 increases LIN-17/Fz activity at the expense of LIN-18/Ryk, thus making the contribution of these signals unequal. For P7.p to polarize correctly and form a proper vulva, LIN-17/Fz and LIN-18/Ryk antagonize other Wnt transmembrane systems VANG-1/VanGogh and CAM-1/Ror. Our genetic data suggest that LIN-17/Fz represses both VANG-1/VanGogh and CAM-1/Ror, while LIN-18/Ryk represses only VANG-1. These data expand our knowledge of a sophisticated signaling network to control P7.p polarity, and suggests that CHW-1 can alter ligand gradients or receptor priorities in the system. PMID:26208319

  3. The C. elegans Chp/Wrch Ortholog CHW-1 Contributes to LIN-18/Ryk and LIN-17/Frizzled Signaling in Cell Polarity.

    PubMed

    Kidd, Ambrose R; Muñiz-Medina, Vanessa; Der, Channing J; Cox, Adrienne D; Reiner, David J

    2015-01-01

    Wnt signaling controls various aspects of developmental and cell biology, as well as contributing to certain cancers. Expression of the human Rho family small GTPase Wrch/RhoU is regulated by Wnt signaling, and Wrch and its paralog Chp/RhoV are both implicated in oncogenic transformation and regulation of cytoskeletal dynamics. We performed developmental genetic analysis of the single Caenorhabditis elegans ortholog of Chp and Wrch, CHW-1. Using a transgenic assay of the distal tip cell migration, we found that wild-type CHW-1 is likely to be partially constitutively active and that we can alter ectopic CHW-1-dependent migration phenotypes with mutations predicted to increase or decrease intrinsic GTP hydrolysis rate. The vulval P7.p polarity decision balances multiple antagonistic Wnt signals, and also uses different types of Wnt signaling. Previously described cooperative Wnt receptors LIN-17/Frizzled and LIN-18/Ryk orient P7.p posteriorly, with LIN-17/Fz contributing approximately two-thirds of polarizing activity. CHW-1 deletion appears to equalize the contributions of these two receptors. We hypothesize that CHW-1 increases LIN-17/Fz activity at the expense of LIN-18/Ryk, thus making the contribution of these signals unequal. For P7.p to polarize correctly and form a proper vulva, LIN-17/Fz and LIN-18/Ryk antagonize other Wnt transmembrane systems VANG-1/VanGogh and CAM-1/Ror. Our genetic data suggest that LIN-17/Fz represses both VANG-1/VanGogh and CAM-1/Ror, while LIN-18/Ryk represses only VANG-1. These data expand our knowledge of a sophisticated signaling network to control P7.p polarity, and suggests that CHW-1 can alter ligand gradients or receptor priorities in the system.

  4. Lin28B and Let-7 in the Control of Sympathetic Neurogenesis and Neuroblastoma Development.

    PubMed

    Hennchen, Melanie; Stubbusch, Jutta; Abarchan-El Makhfi, Ikram; Kramer, Marco; Deller, Thomas; Pierre-Eugene, Cécile; Janoueix-Lerosey, Isabelle; Delattre, Olivier; Ernsberger, Uwe; Schulte, Johannes B; Rohrer, Hermann

    2015-12-16

    The RNA binding protein Lin28B is expressed in developing tissues and sustains stem and progenitor cell identity as a negative regulator of the Let-7 family of microRNAs, which induces differentiation. Lin28B is activated in neuroblastoma (NB), a childhood tumor in sympathetic ganglia and adrenal medulla. Forced expression of Lin28B in embryonic mouse sympathoadrenal neuroblasts elicits postnatal NB formation. However, the normal function of Lin28B in the development of sympathetic neurons and chromaffin cells and the mechanisms involved in Lin28B-induced tumor formation are unclear. Here, we demonstrate a mirror-image expression of Lin28B and Let-7a in developing chick sympathetic ganglia. Lin28B expression is not restricted to undifferentiated progenitor cells but, is observed in proliferating noradrenergic neuroblasts. Lin28 knockdown in cultured sympathetic neuroblasts decreases proliferation, whereas Let-7 inhibition increases the proportion of neuroblasts in the cell cycle. Lin28B overexpression enhances proliferation, but only during a short developmental period, and it does not reduce Let-7a. Effects of in vivo Lin28B overexpression were analyzed in the LSL-Lin28B(DBHiCre) mouse line. Sympathetic ganglion and adrenal medulla volume and the expression level of Let-7a were not altered, although Lin28B expression increased by 12- to 17-fold. In contrast, Let-7a expression was strongly reduced in LSL-Lin28B(DbhiCre) NB tumor tissue. These data demonstrate essential functions for endogenous Lin28 and Let-7 in neuroblast proliferation. However, Lin28B overexpression neither sustains neuroblast proliferation nor affects let-7 expression. Thus, in contrast to other pediatric tumors, Lin28B-induced NB is not due to expansion of proliferating embryonic neuroblasts, and Let-7-independent functions are implicated during initial NB development. Lin28A/B proteins are highly expressed in early development and maintain progenitor cells by blocking the biogenesis and

  5. ESDAPT - APT PROGRAMMING EDITOR AND INTERPRETER

    NASA Technical Reports Server (NTRS)

    Premack, T.

    1994-01-01

    ESDAPT is a graphical programming environment for developing APT (Automatically Programmed Tool) programs for controlling numerically controlled machine tools. ESDAPT has a graphical user interface that provides the user with an APT syntax sensitive text editor and windows for displaying geometry and tool paths. APT geometry statement can also be created using menus and screen picks. ESDAPT interprets APT geometry statements and displays the results in its view windows. Tool paths are generated by batching the APT source to an APT processor (COSMIC P-APT recommended). The tool paths are then displayed in the view windows. Hardcopy output of the view windows is in color PostScript format. ESDAPT is written in C-language, yacc, lex, and XView for use on Sun4 series computers running SunOS. ESDAPT requires 4Mb of disk space, 7Mb of RAM, and MIT's X Window System, Version 11 Release 4, or OpenWindows version 3 for execution. Program documentation in PostScript format and an executable for OpenWindows version 3 are provided on the distribution media. The standard distribution medium for ESDAPT is a .25 inch streaming magnetic tape cartridge (Sun QIC-24) in UNIX tar format. This program was developed in 1992.

  6. Editors' message--Hydrogeology Journal in 2003

    USGS Publications Warehouse

    Voss, Clifford; Olcott, Perry; Schneider, Robert

    2004-01-01

    Hydrogeology Journal appeared in six issues containing a total of 710 pages and 48 major articles, including 31 Papers and 14 Reports, as well as some Technical Notes and Book Reviews. The number of submitted manuscripts continues to increase. The final issue of 2003 also contained the annual volume index. Hydrogeology Journal (HJ) is an international forum for hydrogeology and related disciplines and authors in 2003 were from about 28 countries. Articles advanced hydrogeologic science and described hydrogeologic systems in many regions worldwide. These articles focused on a variety of general topics and on studies of hydrogeology in 24 countries: Afghanistan, Algeria, Argentina, Australia, Bangladesh, Belgium, Canada, Chile, China, Denmark, France, India, Italy, Mexico, Netherlands, New Zealand, Nigeria, Norway, Portugal, Russia, South Africa, Switzerland, Turkey, and U.S.A. The Guest Editor of the 2003 HJ theme issue on “Hydromechanics in Geology and Geotechnics”, Ove Stephansson, assembled a valuable collection of technical reviews and research papers from eminent authors on important aspects of the subject area.

  7. Retirement of J. Gary Eden as Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Jagadish, Chennupati; Jelinkova, Helena; Fainman, Yeshaiahu; Dawson, Martin; Ermers, Ysabel

    2016-01-01

    After nine years of dedicated service as Editor-in-Chief of Progress in Quantum Electronics (PQE), J. Gary Eden has retired at the end of December 2015. During his term as the Editor-in-Chief, PQE has grown significantly in size and quality and he has given generously of his time in advising authors, referees, editors, and the journal staff. Gary is an exceptional scientist and a generous individual who has given so much to the community. He is always very positive in every situation, and has created positive environment and supported people with utmost enthusiasm.

  8. Martin Stutzmann: Editor, Teacher, Scientist and Friend

    NASA Astrophysics Data System (ADS)

    Cardona, Manuel

    2005-02-01

    On 2 January 1995 Martin Stutzmann became Editor-in-Chief of physica status solidi, replacing Professor E. Gutsche, who had led the journal through the stormy period involving the fall of the Iron Curtain, the unification of Germany and the change in its Eastern part, where physica status solidi was based, from socialism as found in the real world (a German concept) to real world capitalism. In 1995 it was thought that the process had been completed (we should have known better!) and after the retirement of Prof. Gutsche the new owners of physica status solidi (Wiley-VCH) decided that a change in scientific management was desirable to adapt to the new socio-political facts and to insure the scientific continuity of the journal.Martin had moved in 1993 from my department at the Max-Planck-Institute to Munich where he soon displayed a tremendous amount of science man- agement ability during the build-up of the Walter Schottky Institute. The search for a successor as Edi- tor-in-Chief was not easy: the job was not very glamorous after the upheavals which had taken place in the editorial world following the political changes. Somebody in the Editorial Boards must have suggested Martin Stutzmann. I am sure that there was opposition: one usually looks for a well-established person ready to leave his direct involvement in science and take up a new endeavor of a more administrative nature. Nevertheless, the powers that be soon realized that Martin was an excellent, if somewhat unconventional candidate who had enough energy to remain a topnotch scientist and to lead the journal in the difficult times ahead: he was offered the job. In the negotiations that followed, he insisted in getting the administrative structures that would allow him to improve the battered quality of the journal and to continue his scientific productivity. Today we are happy to see that he succeeded in both endeavors. The journal has since grown in size and considerably improved its quality

  9. EDITORIAL: Incoming Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Webb, Steve

    2006-01-01

    Physics in Medicine and Biology (PMB) is a journal that originated in the UK but is now rightly regarded as one of the pre-eminent international journals for the publication of material coming within its remit. It is 50 years old and its maturity is an outcome of the consistent support of high performing authors, a supportive and professional publishing house, dedicated referees, many vigorous and conscientious editorial boards and the collective input of the 10 previous Editors as listed in his incoming editorial (January 2000 issue) by the retiring Editor, Professor Alun Beddoe. The scientific climate and it associated publication modus operandi in the 1950s was very different from that at the current time and the journal has evolved to reflect this. Hence today the scope of content is somewhat broader, the size of the journal is vastly greater, the whole publication process is slicker and more efficient and a paper in PMB is highly prized by its authors and those who look to quality factors and impact. The quality of the journal still relies on the voluntary labour and expertise of its busy international referees and Board members. For many years I have tried to place my own research material in PMB and encourage my teams to do likewise, not only acknowledging the prestige of the journal but also because of the extraordinarily fast turnaround time of all the processes without any loss of quality. This serves us very well and the publishing team are to be congratulated. Some things seem to change more slowly or not at all, however. The prediction, when I started my research career, that books and journals would be dinosaurs by now has manifestly not come true and, whilst most of us are addicted (and why not?) to the electronic ways of doing things that can be done by more traditional ways, PMB and a packet of reprints from time to time arriving by post still has a reassuring feel despite the fact that the papers have been `on-line' for a while before. An incoming

  10. Editorial independence and the editor-owner relationship: good editors never die, they just cross the line.

    PubMed

    Lapeña, J F

    2009-12-01

    The concept of editorial freedom or independence is examined in the light of the editor-owner relationship. Like individual and national freedom or independence, it is a rhetorical concept whose realisation flows from internal achievement as much as it depends on external validation. This freedom entails roles and responsibilities embodied in specific codes of practice for editors, such as the guidelines espoused by the International Committee of Medical Journal Editors and the World Association of Medical Editors. The calling to embody these guidelines makes editing a vocation that demands isolation and distancing, separation and solitude. It involves bracketing one's biases, prejudgments and preconceptions. With such detachment comes real freedom; one that requires a moral fibre and trustworthiness that uphold truth and right, whether in full view of public scrutiny, or in the aloneness of private secrecy. The stereotypical tension between academic and commercial concerns highlights the editor-owner relationship, and bears directly on editorial independence. In practice, journal owners overstep their prerogatives. The absence of clear contracts defining editorial independence and the lack of established mechanisms governing the editor-owner relationship affect many small- to medium-sized journals in developing countries. Even large journals in developed and democratic nations or totalitarian states and societies are not spared. At the end of the day, editorial freedom exists only insofar as it is tolerated, or until editors cross the line.

  11. Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A.

    PubMed

    Park, Chan Hyuk; Lee, Jung Hwa; Lee, Na Keum; Lee, Yong Chan; Lee, Sang Kil

    2016-09-15

    Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer.

  12. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism.

    PubMed

    Shinoda, Gen; Shyh-Chang, Ng; Soysa, T Yvanka de; Zhu, Hao; Seligson, Marc T; Shah, Samar P; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P; Gregory, Richard I; Asara, John M; Cantley, Lewis C; Moss, Eric G; Daley, George Q

    2013-08-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. Copyright © 2013 AlphaMed Press.

  13. Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

    PubMed Central

    Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

  14. Blurred Boundaries: The RNA Binding Protein Lin28A Is Also an Epigenetic Regulator.

    PubMed

    Tan, Frederick E; Yeo, Gene W

    2016-01-07

    Lin28A is best known as a post-transcriptional regulator of gene expression. In this issue, Zeng et al. (2016) show that Lin28A has an unexpected role as an epigenetic regulator of DNA. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1.

    PubMed

    Ma, Xiaoyu; Li, Chenchen; Sun, Linchong; Huang, De; Li, Tingting; He, Xiaoping; Wu, Gongwei; Yang, Zheng; Zhong, Xiuying; Song, Libing; Gao, Ping; Zhang, Huafeng

    2014-10-10

    Aberrant expression of Lin28 and let-7 has been observed in many human malignancies. However, its functions and underlying mechanisms remain largely elusive. Here we show that aberrant expression of Lin28 and let-7 facilitates aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we discover that Lin28A and Lin28B enhance, whereas let-7 suppresses, aerobic glycolysis via targeting pyruvate dehydrogenase kinase 1, or PDK1, in a hypoxia- or hypoxia-inducible factor-1 (HIF-1)-independent manner, illustrating a novel pathway to mediate aerobic glycolysis of cancer cells even in ambient oxygen levels. Importantly, we further demonstrate that PDK1 is critical for Lin28A- and Lin28B-mediated cancer proliferation both in vitro and in vivo, establishing a previously unappreciated mechanism by which Lin28/let-7 axis facilitates Warburg effect to promote cancer progression. Our findings suggest a potential rationale to target PDK1 for cancer therapy in malignancies with aberrant expression of Lin28 and let-7.

  16. Lin28A binds active promoters and recruits Tet1 to regulate gene expression

    PubMed Central

    Zeng, Yaxue; Yao, Bing; Shin, Jaehoon; Lin, Li; Kim, Namshik; Song, Qifeng; Liu, Shuang; Su, Yijing; Guo, Junjie U.; Huang, Luoxiu; Wan, Jun; Wu, Hao; Qian, Jiang; Cheng, Xiaodong; Zhu, Heng; Ming, Guo-li; Jin, Peng; Song, Hongjun

    2015-01-01

    Lin28, a well-known RNA-binding protein, regulates diverse cellular properties. All physiological functions of Lin28A characterized so far have been attributed to its repression of let-7 miRNA biogenesis or modulation of mRNA translational efficiency. Here we show that Lin28A directly binds to a consensus DNA sequence in vitro and in mouse embryonic stem cells in vivo. ChIP-seq and RNA-seq reveal enrichment of Lin28A binding around transcription start sites, and a positive correlation between its genomic occupancy and expression of many associated genes. Mechanistically, Lin28A recruits 5-methylcytosine-dioxygenase Tet1 to genomic binding sites to orchestrate 5-methylcytosine and 5-hydroxymethylcytosine dynamics. Either Lin28A or Tet1 knockdown leads to dysregulated DNA methylation and expression of common target genes. These results reveal a surprising role for Lin28A in transcriptional regulation via epigenetic DNA modifications and have implications for understanding mechanisms underlying versatile functions of Lin28A in mammalian systems. PMID:26711009

  17. Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A

    PubMed Central

    Park, Chan Hyuk; Lee, Jung Hwa; Lee, Na Keum; Lee, Yong Chan; Lee, Sang Kil

    2016-01-01

    Background/Aims Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. Methods LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. Results The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. Conclusions The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer. PMID:26893371

  18. Lin28A Binds Active Promoters and Recruits Tet1 to Regulate Gene Expression.

    PubMed

    Zeng, Yaxue; Yao, Bing; Shin, Jaehoon; Lin, Li; Kim, Namshik; Song, Qifeng; Liu, Shuang; Su, Yijing; Guo, Junjie U; Huang, Luoxiu; Wan, Jun; Wu, Hao; Qian, Jiang; Cheng, Xiaodong; Zhu, Heng; Ming, Guo-li; Jin, Peng; Song, Hongjun

    2016-01-07

    Lin28, a well-known RNA-binding protein, regulates diverse cellular properties. All physiological functions of Lin28A characterized so far have been attributed to its repression of let-7 miRNA biogenesis or modulation of mRNA translational efficiency. Here we show that Lin28A directly binds to a consensus DNA sequence in vitro and in mouse embryonic stem cells in vivo. ChIP-seq and RNA-seq reveal enrichment of Lin28A binding around transcription start sites and a positive correlation between its genomic occupancy and expression of many associated genes. Mechanistically, Lin28A recruits 5-methylcytosine-dioxygenase Tet1 to genomic binding sites to orchestrate 5-methylcytosine and 5-hydroxymethylcytosine dynamics. Either Lin28A or Tet1 knockdown leads to dysregulated DNA methylation and expression of common target genes. These results reveal a surprising role for Lin28A in transcriptional regulation via epigenetic DNA modifications and have implications for understanding mechanisms underlying versatile functions of Lin28A in mammalian systems. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development

    PubMed Central

    Vogt, Edgar J.; Meglicki, Maciej; Hartung, Kristina Ilka; Borsuk, Ewa; Behr, Rüdiger

    2012-01-01

    The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development. PMID:23172912

  20. RNA-binding protein LIN28 is a sensitive marker of ovarian primitive germ cell tumours.

    PubMed

    Xue, Debin; Peng, Yan; Wang, Fenghua; Allan, Robert W; Cao, Dengfeng

    2011-09-01

    LIN28 is an RNA-binding protein that has been detected in testicular germ cell tumours (GCTs), but its status in ovarian GCTs is unknown. The aim was to determine the immunohistochemical profile of LIN28 in ovarian GCTs. Immunohistochemistry of LIN28 was performed in 110 primary and 11 metastatic ovarian GCTs. The percentage of tumour cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%). To determine its specificity, we stained LIN28 in 119 non-GCTs, including 37 clear cell carcinomas. Strong 4+ LIN28 staining was seen in 4/4 (100%) gonadoblastomas, 7/7 (100%) embryonal carcinomas (ECs), and 41/41 (100%) yolk sac tumours (YSTs). Among 39 dysgerminomas, 4+ staining was seen in 37 and 3+ staining in two (strong in 37; mixed weak and strong in two). Twelve of 14 immature teratomas showed variable LIN28 staining (1+ to 4+) in the immature neuroepithelium (weak to strong staining), whereas mature teratomas, carcinoids, struma ovarii and strumal carcinoids were negative. Only 5/117 non-GCTs (1/37 clear cell carcinomas) showed weak to moderate 1-2+ staining. LIN28 is a sensitive marker for gonadoblastomas, dysgerminomas, ECs, and YSTs. LIN28 can be used to distinguish them from non-GCTs. © 2011 Blackwell Publishing Limited.

  1. Evidence that Lin28 stimulates translation by recruiting RNA helicase A to polysomes.

    PubMed

    Jin, Jianyu; Jing, Wei; Lei, Xin-Xiang; Feng, Chen; Peng, Shuping; Boris-Lawrie, Kathleen; Huang, Yingqun

    2011-05-01

    The stem cell protein Lin28 functions to inhibit the biogenesis of a group of miRNAs but also stimulates the expression of a subset of mRNAs at the post-transcriptional level, the underlying mechanism of which is not yet understood. Here we report the characterization of the molecular interplay between Lin28 and RNA helicase A (RHA) known to play an important role in remodeling ribonucleoprotein particles during translation. We show that reducing Lin28 expression results in decreased RHA association with polysomes while increasing Lin28 expression leads to elevated RHA association. Further, the carboxyl terminus of Lin28 is necessary for interaction with both the amino and carboxyl termini of RHA. Importantly, a carboxyl terminal deletion mutant of Lin28 that retains RNA-binding activity fails to interact with RHA and exhibits dominant-negative effects on Lin28-dependent stimulation of translation. Taken together, these results lead us to suggest that Lin28 may stimulate translation by actively recruiting RHA to polysomes. © The Author(s) 2011. Published by Oxford University Press.

  2. Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.

    PubMed

    Vogt, Edgar J; Meglicki, Maciej; Hartung, Kristina Ilka; Borsuk, Ewa; Behr, Rüdiger

    2012-12-01

    The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.

  3. Evidence that Lin28 stimulates translation by recruiting RNA helicase A to polysomes

    PubMed Central

    Jin, Jianyu; Jing, Wei; Lei, Xin-Xiang; Feng, Chen; Peng, Shuping; Boris-Lawrie, Kathleen; Huang, Yingqun

    2011-01-01

    The stem cell protein Lin28 functions to inhibit the biogenesis of a group of miRNAs but also stimulates the expression of a subset of mRNAs at the post-transcriptional level, the underlying mechanism of which is not yet understood. Here we report the characterization of the molecular interplay between Lin28 and RNA helicase A (RHA) known to play an important role in remodeling ribonucleoprotein particles during translation. We show that reducing Lin28 expression results in decreased RHA association with polysomes while increasing Lin28 expression leads to elevated RHA association. Further, the carboxyl terminus of Lin28 is necessary for interaction with both the amino and carboxyl termini of RHA. Importantly, a carboxyl terminal deletion mutant of Lin28 that retains RNA-binding activity fails to interact with RHA and exhibits dominant-negative effects on Lin28-dependent stimulation of translation. Taken together, these results lead us to suggest that Lin28 may stimulate translation by actively recruiting RHA to polysomes. PMID:21247876

  4. Important amino acid residues of hexachlorocyclohexane dehydrochlorinases (LinA) for enantioselective transformation of hexachlorocyclohexane isomers.

    PubMed

    Shrivastava, Nidhi; Macwan, Ankit S; Kohler, Hans-Peter E; Kumar, Ashwani

    2017-03-01

    LinA-type1 and LinA-type2 are two well-characterized variants of the enzyme 'hexachlorocyclohexane (HCH)-dehydrochlorinase'. They differ from each other at ten amino acid positions and exhibit differing enantioselectivity for the transformation of the (-) and (+) enantiomers of α-HCH. Amino acids responsible for this enantioselectivity, however, are not known. An in silico docking analysis identified four amino acids (K20, L96, A131, and T133) in LinA-type1 that could be involved in selective binding of the substrates. Experimental studies with constructed mutant enzymes revealed that a combined presence of three amino acid changes in LinA-type1, i.e. K20Q, L96C, and A131G, caused a reversal in its preference from the (-) to the (+) enantiomer of α-HCH. This preference was enhanced by the additional amino acid change T133 M. Presence of these four changes also caused the reversal of enantioselectivity of LinA-type1 for δ-HCH, and β-, γ-, and δ-pentachlorocyclohexens. Thus, the residues K20, L96, A131, and T133 in LinA-type1 and the residues Q20, C96, G131, and M133 in LinA-type 2 appear to be important determinants for the enantioselectivity of LinA enzymes.

  5. 78 FR 30332 - Manufacturer of Controlled Substances, Notice of Application, Lin Zhi International, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... Enforcement Administration Manufacturer of Controlled Substances, Notice of Application, Lin Zhi International... that on April 3, 2013, Lin Zhi International, Inc., 670 Almanor Avenue, Sunnyvale, California 94085... (9193) II Methadone (9250) II Dextropropoxyphene, bulk (non-dosage forms) II (9273). Morphine (9300)...

  6. 77 FR 30326 - Manufacturer of Controlled Substances; Notice of Application; Lin Zhi International Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Lin Zhi International... that on April 19, 2012, Lin Zhi International Inc., 670 Almanor Avenue, Sunnyvale, California 94085... (9193) II Methadone (9250) II Dextropropoxyphene, bulk (non-dosage forms) II (9273). Morphine (9300)...

  7. LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans.

    PubMed

    Shaye, Daniel D; Greenwald, Iva

    2005-11-01

    A novel mode of crosstalk between the EGFR-Ras-MAPK and LIN-12/Notch pathways occurs during the patterning of a row of vulval precursor cells (VPCs) in Caenorhabditis elegans: activation of the EGFR-Ras-MAPK pathway in the central VPC promotes endocytosis and degradation of LIN-12 protein. LIN-12 downregulation in the central VPC is a prerequisite for the activity of the lateral signal, which activates LIN-12 in neighboring VPCs. Here we characterize cis-acting targeting sequences in the LIN-12 intracellular domain and find that in addition to a di-leucine motif, serine/threonine residues are important for internalization and lysine residues are important for post-internalization trafficking and degradation. We also identify two trans-acting factors that are required for post-internalization trafficking and degradation: ALX-1, a homolog of yeast Bro1p and mammalian Alix and the WWP-1/Su(dx)/Itch ubiquitin ligase. By examining the effects of mutated forms of LIN-12 and reduced wwp-1 or alx-1 activity on subcellular localization and activity of LIN-12, we provide evidence that the lateral signal-inhibiting activity of LIN-12 resides in the extracellular domain and occurs at the apical surface of the VPCs.

  8. Bibliography or Bust: The "Angst" of Scholarly Editors.

    ERIC Educational Resources Information Center

    Costa, Richard Hauer

    1980-01-01

    Provides evidence indicating not only that the market for articles on literature and language is saturated with submissions, but that the glut creates burgeoning problems for editors, including the problem of rejecting publishable items. (RL)

  9. The Letters Not Sent by a Journal Editor

    NASA Astrophysics Data System (ADS)

    2013-04-01

    In the late hours of the night, even the most conscientious of journal editors may slip into writing imaginary letters to cherished authors and reviewers. Here are some of the letters that I composed:

  10. ANNOUNCEMENT: Greetings from the Editor and Publisher

    NASA Astrophysics Data System (ADS)

    Wäppling, Roger; Williams, Sarah

    2006-01-01

    Physica Scripta is an international physics journal published for the Royal Swedish Academy of Sciences on behalf of the Nordic Science Academies and Physical Societies. This issue marks the beginning of the partnership between the Royal Swedish Academy of Sciences and Institute of Physics Publishing (IOP). We look forward to a fruitful relationship in which Physica Scripta can profit from the international reach of IOP. Authors and readers will benefit from advance publication of articles on the web prior to receiving each month's journal issue. The peer-review system will continue to be managed by Professor Roger Wäppling who will assess each paper before assigning it to an external editor or sending it for refereeing. IOP will receive new article submissions and generate electronic documents suitable for use in the refereeing process. The editorial office in Sweden will then be responsible for these manuscripts up to the final publication decision. Accepted articles will be sent to IOP for copy-editing, typesetting, production and distribution. We aim to provide our authors, referees and readers with an enhanced service for this well-established journal. IOP will maintain and augment Physica Scripta's record in publishing a broad range of high-quality research papers and we will continue to publish Topical Issues as supplements to the regular 12 issues. The popular Comments articles will continue to be published in conjunction with regular papers under this new partnership. We hope that our subscribers will continue to enjoy reading Physica Scripta as a valuable resource for general physics research.

  11. EDITORIAL: A Message from the Editor

    NASA Astrophysics Data System (ADS)

    Hudson, R. P.

    1981-04-01

    As the new Editor of Metrologia, I welcome this opportunity to greet the readers, to say a few words on hopes and plans, and to make both a plea and promise. The plea arises from a perception that, despite its sixteen years of existence, this journal does not yet enjoy a status of intimate familiarity throughout the world community of physicists. Nevertheless, having been established as a vehicle for disseminating knowledge on all matters metrological, it offers a unique communication and archival resource to those who are active in advancing the science (and the art) of accurate measurement. Therefore I beseech all readers to lose no opportunity to submit their finest metrology research reports and their most penetrating metrological ruminations for publication here and—highly important—to encourage their unaware colleagues to do likewise. And, as a journal cannot flourish which is not fully responsive to the needs of its clientele, my promise is to bend every effort to achieving prompt and careful review of your submissions and rapid publication for those accepted. It is my hope and intention, furthermore, to bring about a measure of increased variety of content through occasional seminal review articles, news of major publications and forthcoming conferences, news of current research and development that should be of major interest to the readership well before the publication of its results; and through the inclusion of short communications on research, letters and topics of wide interest, and comments on articles published. In order to successfully promote these aims, your specific contributions and your suggestions for improvements are enthusiastically solicited. Finally, let me record my gratitude to the distinguished scientists who have agreed to serve for a term on the Editorial Board, to assist me in my task and to labour in the interests of you all. Each member of that Board stands ready to assist the readership on any matter pertaining to

  12. The WebACS - An Accessible Graphical Editor.

    PubMed

    Parker, Stefan; Nussbaum, Gerhard; Pölzer, Stephan

    2017-01-01

    This paper is about the solution to accessibility problems met when implementing a graphical editor, a major challenge being the comprehension of the relationships between graphical components, which needs to be guaranteed for blind and vision impaired users. In the concrete case the HTML5 canvas and Javascript were used. Accessibility was reached by implementing a list view of elements, which also enhances the usability of the editor.

  13. Adapting a thesis to publication style: meeting editors' expectations.

    PubMed

    Johnson, S H

    1996-01-01

    Every year hundreds of thesis reports are completed by graduate students. Many of these end up on nursing journal editors' desks, only to be rejected. What characteristics of a thesis lead to rejection? How can authors develop quality research manuscripts? How can faculty teach graduate students the difference between a thesis and manuscript. This article answers these questions by providing advice from 15 critical care and research journal editors.

  14. Substrate Utilization in the Critically Ill (Letter to the Editor)

    DTIC Science & Technology

    2009-02-01

    pen.sagepub.com/ Nutrition Journal of Parenteral and Enteral http://pen.sagepub.com/content/33/1/111 The online version of this article can be found at: DOI...Published by: http://www.sagepublications.com On behalf of: The American Society for Parenteral & Enteral Nutrition can be found at:Journal of...the Editor Dear Editor, Journal of Parenteral and Enteral Nutrition Volume 33 Number 1 January/February 2009 111 © 2009 American Society for Parenteral

  15. Lin28 and let-7 in the Metabolic Physiology of Aging.

    PubMed

    Jun-Hao, Elwin Tan; Gupta, Renuka Ravi; Shyh-Chang, Ng

    2016-03-01

    The Lin28/let-7 molecular switch has emerged as a central regulator of growth signaling pathways and metabolic enzymes. Initially discovered to regulate developmental timing in the nematode, the Lin28/let-7 pathway of RNA regulation has gained prominence for its role in mammalian stem cells, cancer cells, tissue development, and aging. By regulating RNAs, the pathway coordinates cellular growth and cellular metabolism to influence metabolic physiology. Here, we review this regulatory mechanism and its impact on cancers, which reactivate Lin28, cardiovascular diseases, which implicate let-7, human genome-wide association studies (GWAS) of growth, and metabolic diseases, which implicate the Lin28/let-7 pathway. We also highlight questions relating to Barker's Hypothesis and the potential actions of the Lin28/let-7 pathway on programming long-lasting epigenetic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. ZED- A LINE EDITOR FOR THE DEC VAX

    NASA Technical Reports Server (NTRS)

    Scott, P. J.

    1994-01-01

    The ZED editor for the DEC VAX is a simple, yet powerful line editor for text, program source code, and non-binary data. Line editors can be superior to screen editors in some cases, such as executing complex multiple or conditional commands, or editing via slow modem lines. ZED excels in the area of text processing by using procedure files. For example, such procedures can reformat a file of addresses or remove all comment lines from a FORTRAN program. In addition to command files, ZED also features versatile search qualifiers, global changes, conditionals, on-line help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. The ZED editor was originally developed at Cambridge University in London and has been continuously enhanced since 1976. Users of the Cambridge implementation have devised such elaborate ZED procedures as chess games, calculators, and programs for evaluating Pi. This implementation of ZED strives to maintain the characteristics of the Cambridge editor. A complete ZED manual is included on the tape. ZED is written entirely in C for either batch or interactive execution on the DEC VAX under VMS 4.X and requires 80,896 bytes of memory. This program was released in 1988 and updated in 1989.

  17. ZED- A LINE EDITOR FOR THE DEC VAX

    NASA Technical Reports Server (NTRS)

    Scott, P. J.

    1994-01-01

    The ZED editor for the DEC VAX is a simple, yet powerful line editor for text, program source code, and non-binary data. Line editors can be superior to screen editors in some cases, such as executing complex multiple or conditional commands, or editing via slow modem lines. ZED excels in the area of text processing by using procedure files. For example, such procedures can reformat a file of addresses or remove all comment lines from a FORTRAN program. In addition to command files, ZED also features versatile search qualifiers, global changes, conditionals, on-line help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. The ZED editor was originally developed at Cambridge University in London and has been continuously enhanced since 1976. Users of the Cambridge implementation have devised such elaborate ZED procedures as chess games, calculators, and programs for evaluating Pi. This implementation of ZED strives to maintain the characteristics of the Cambridge editor. A complete ZED manual is included on the tape. ZED is written entirely in C for either batch or interactive execution on the DEC VAX under VMS 4.X and requires 80,896 bytes of memory. This program was released in 1988 and updated in 1989.

  18. Increased expression of Lin28B associates with poor prognosis in patients with oral squamous cell carcinoma.

    PubMed

    Wu, Tianfu; Jia, Jun; Xiong, Xuepeng; He, Haijun; Bu, Linlin; Zhao, Zhili; Huang, Congfa; Zhang, Wenfeng

    2013-01-01

    Recent studies showed that incomplete cell reprogramming can transform cells into tumour-like cells. Lin28A is associated with fibroblast and sarcoma cell reprogramming, whereas its homologue Lin28B is associated with hematopoietic cell reprogramming. This study aimed to investigate the expression and prognostic difference between Lin28A and Lin28B in oral squamous cell carcinoma (OSCC). Expression level was assessed by immunohistochemistry and staining location was confirmed by immunofluorescence. Prognostic values were analysed and compared by the Kaplan-Meier analysis and uni and multivariate Cox regression models. Besides, in vitro cell assays and in vivo nude mice xenograft were used to demonstrate the influence of increased Lin28B expression in OSCC. Lin28A and Lin28B expression increased in OSCC, and co-expression of Lin28A and Lin28B showed no significant association with patient prognosis. Kaplan-Meier analysis showed that patients with high Lin28B but not Lin28A expression had lower overall survival (OS) rates than those with low Lin28B expression. Further Univariate analysis showed that patients with increased Lin28B expression had shorter disease-free survival (DFS) and shorter OS, while multivariate analysis showed Lin28B overexpression with TNM stage predicted poor prognosis in patients with OSCC. Besides, stable expressing Lin28B in oral cancer cells promoted cell migration, invasion, colony formation, in vivo proliferation and increased the expression of cancer suppressor miRNA let-7 targeted genes IL-6, HMGA2, the EMT markers Snail and Twist, the angiogenesis inducer VEGF, and the apoptosis inhibitor Survivin. These combined results indicate that Lin28B is a novel marker for predicting prognosis in patients with OSCC and may be a therapeutic target.

  19. LIN-42, the Caenorhabditis elegans PERIOD homolog, Negatively Regulates MicroRNA Transcription

    PubMed Central

    Aguirre-Chen, Cristina; Hammell, Christopher M.

    2014-01-01

    During C. elegans development, microRNAs (miRNAs) function as molecular switches that define temporal gene expression and cell lineage patterns in a dosage-dependent manner. It is critical, therefore, that the expression of miRNAs be tightly regulated so that target mRNA expression is properly controlled. The molecular mechanisms that function to optimize or control miRNA levels during development are unknown. Here we find that mutations in lin-42, the C. elegans homolog of the circadian-related period gene, suppress multiple dosage-dependent miRNA phenotypes including those involved in developmental timing and neuronal cell fate determination. Analysis of mature miRNA levels in lin-42 mutants indicates that lin-42 functions to attenuate miRNA expression. Through the analysis of transcriptional reporters, we show that the upstream cis-acting regulatory regions of several miRNA genes are sufficient to promote highly dynamic transcription that is coupled to the molting cycles of post-embryonic development. Immunoprecipitation of LIN-42 complexes indicates that LIN-42 binds the putative cis-regulatory regions of both non-coding and protein-coding genes and likely plays a role in regulating their transcription. Consistent with this hypothesis, analysis of miRNA transcriptional reporters in lin-42 mutants indicates that lin-42 regulates miRNA transcription. Surprisingly, strong loss-of-function mutations in lin-42 do not abolish the oscillatory expression patterns of lin-4 and let-7 transcription but lead to increased expression of these genes. We propose that lin-42 functions to negatively regulate the transcriptional output of multiple miRNAs and mRNAs and therefore coordinates the expression levels of genes that dictate temporal cell fate with other regulatory programs that promote rhythmic gene expression. PMID:25032706

  20. Caenorhabditis elegans period homolog lin-42 regulates the timing of heterochronic miRNA expression.

    PubMed

    McCulloch, Katherine A; Rougvie, Ann E

    2014-10-28

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally via the 3' UTR of target mRNAs and were first identified in the Caenorhabditis elegans heterochronic pathway. miRNAs have since been found in many organisms and have broad functions, including control of differentiation and pluripotency in humans. lin-4 and let-7-family miRNAs regulate developmental timing in C. elegans, and their proper temporal expression ensures cell lineage patterns are correctly timed and sequentially executed. Although much is known about miRNA biogenesis, less is understood about how miRNA expression is timed and regulated. lin-42, the worm homolog of the circadian rhythm gene period of flies and mammals, is another core component of the heterochronic gene pathway. lin-42 mutants have a precocious phenotype, in which later-stage programs are executed too early, but the placement of lin-42 in the timing pathway is unclear. Here, we demonstrate that lin-42 negatively regulates heterochronic miRNA transcription. let-7 and the related miRNA miR-48 accumulate precociously in lin-42 mutants. This defect reflects transcriptional misregulation because enhanced expression of both primary miRNA transcripts (pri-miRNAs) and a let-7 promoter::gfp fusion are observed. The pri-miRNA levels oscillate during larval development, in a pattern reminiscent of lin-42 expression. Importantly, we show that lin-42 is not required for this cycling; instead, peak amplitude is increased. Genetic analyses further confirm that lin-42 acts through let-7 family miRNAs. Taken together, these data show that a key function of lin-42 in developmental timing is to dampen pri-miRNAs levels, preventing their premature expression as mature miRNAs.

  1. LIN-42, the Caenorhabditis elegans PERIOD homolog, negatively regulates microRNA transcription.

    PubMed

    Perales, Roberto; King, Dana M; Aguirre-Chen, Cristina; Hammell, Christopher M

    2014-07-01

    During C. elegans development, microRNAs (miRNAs) function as molecular switches that define temporal gene expression and cell lineage patterns in a dosage-dependent manner. It is critical, therefore, that the expression of miRNAs be tightly regulated so that target mRNA expression is properly controlled. The molecular mechanisms that function to optimize or control miRNA levels during development are unknown. Here we find that mutations in lin-42, the C. elegans homolog of the circadian-related period gene, suppress multiple dosage-dependent miRNA phenotypes including those involved in developmental timing and neuronal cell fate determination. Analysis of mature miRNA levels in lin-42 mutants indicates that lin-42 functions to attenuate miRNA expression. Through the analysis of transcriptional reporters, we show that the upstream cis-acting regulatory regions of several miRNA genes are sufficient to promote highly dynamic transcription that is coupled to the molting cycles of post-embryonic development. Immunoprecipitation of LIN-42 complexes indicates that LIN-42 binds the putative cis-regulatory regions of both non-coding and protein-coding genes and likely plays a role in regulating their transcription. Consistent with this hypothesis, analysis of miRNA transcriptional reporters in lin-42 mutants indicates that lin-42 regulates miRNA transcription. Surprisingly, strong loss-of-function mutations in lin-42 do not abolish the oscillatory expression patterns of lin-4 and let-7 transcription but lead to increased expression of these genes. We propose that lin-42 functions to negatively regulate the transcriptional output of multiple miRNAs and mRNAs and therefore coordinates the expression levels of genes that dictate temporal cell fate with other regulatory programs that promote rhythmic gene expression.

  2. The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans.

    PubMed

    Tocchini, Cristina; Keusch, Jeremy J; Miller, Sarah B; Finger, Susanne; Gut, Heinz; Stadler, Michael B; Ciosk, Rafal

    2014-08-01

    The mechanisms controlling cell fate determination and reprogramming are fundamental for development. A profound reprogramming, allowing the production of pluripotent cells in early embryos, takes place during the oocyte-to-embryo transition. To understand how the oocyte reprogramming potential is controlled, we sought Caenorhabditis elegans mutants in which embryonic transcription is initiated precociously in germ cells. This screen identified LIN-41, a TRIM-NHL protein and a component of the somatic heterochronic pathway, as a temporal regulator of pluripotency in the germline. We found that LIN-41 is expressed in the cytoplasm of developing oocytes, which, in lin-41 mutants, acquire pluripotent characteristics of embryonic cells and form teratomas. To understand LIN-41 function in the germline, we conducted structure-function studies. In contrast to other TRIM-NHL proteins, we found that LIN-41 is unlikely to function as an E3 ubiquitin ligase. Similar to other TRIM-NHL proteins, the somatic function of LIN-41 is thought to involve mRNA regulation. Surprisingly, we found that mutations predicted to disrupt the association of LIN-41 with mRNA, which otherwise compromise LIN-41 function in the heterochronic pathway in the soma, have only minor effects in the germline. Similarly, LIN-41-mediated repression of a key somatic mRNA target is dispensable for the germline function. Thus, LIN-41 appears to function in the germline and the soma via different molecular mechanisms. These studies provide the first insight into the mechanism inhibiting the onset of embryonic differentiation in developing oocytes, which is required to ensure a successful transition between generations.

  3. Distinct expression patterns predict differential roles of the miRNA-binding proteins, Lin28 and Lin28b, in the mouse testis: studies during postnatal development and in a model of hypogonadotropic hypogonadism.

    PubMed

    Gaytan, Francisco; Sangiao-Alvarellos, Susana; Manfredi-Lozano, María; García-Galiano, David; Ruiz-Pino, Francisco; Romero-Ruiz, Antonio; León, Silvia; Morales, Concepción; Cordido, Fernando; Pinilla, Leonor; Tena-Sempere, Manuel

    2013-03-01

    Lin28 (also termed Lin28a) and Lin28b are related RNA-binding proteins, involved in the control of microRNA synthesis, especially of the let-7 family, with putative functions in early (embryo) development. However, their roles during postnatal maturation remain ill defined. Despite the general assumption that Lin28 and Lin28b share similar targets and functions, conclusive demonstration of such redundancy is still missing. In addition, recent observations suggest a role of Lin28 proteins in mammalian reproduction, which is yet to be defined. We document herein the patterns of RNA expression and protein distribution of Lin28 and Lin28b in mouse testis during postnatal development and in a model of hypogonadotropic hypogonadism as a result of inactivation of the kisspeptin receptor, Gpr54. Lin28 and Lin28b mRNAs were expressed in mouse testis across postnatal maturation, but their levels disparately varied between neonatal and pubertal periods, with peak Lin28 levels in infantile testes and sustained elevation of Lin28b mRNA in young adult male gonads, where relative levels of let-7a and let-7b miRNAs were significantly suppressed. In addition, Lin28 peptides displayed totally different patterns of cellular distribution in mouse testis: Lin28 was located in undifferentiated and type-A1 spermatogonia, whereas Lin28b was confined to spermatids and interstitial Leydig cells. These profiles were perturbed in Gpr54 null mouse testis, which showed preserved but irregular Lin28 signal and absence of Lin28b peptide, which was rescued by administration of gonadotropins, mainly hCG (as super-agonist of LH). In addition, increased relative levels of Lin28, but not Lin28b, mRNA and of let-7a/let-7b miRNAs were observed in Gpr54 KO mouse testes. Altogether, our data are the first to document the divergent patterns of cellular distribution and mRNA expression of Lin28 and Lin28b in the mouse testis along postnatal maturation and their alteration in a model of congenital

  4. EzEditor: a versatile sequence alignment editor for both rRNA- and protein-coding genes.

    PubMed

    Jeon, Yoon-Seong; Lee, Kihyun; Park, Sang-Cheol; Kim, Bong-Soo; Cho, Yong-Joon; Ha, Sung-Min; Chun, Jongsik

    2014-02-01

    EzEditor is a Java-based molecular sequence editor allowing manipulation of both DNA and protein sequence alignments for phylogenetic analysis. It has multiple features optimized to connect initial computer-generated multiple alignment and subsequent phylogenetic analysis by providing manual editing with reference to biological information specific to the genes under consideration. It provides various functionalities for editing rRNA alignments using secondary structure information. In addition, it supports simultaneous editing of both DNA sequences and their translated protein sequences for protein-coding genes. EzEditor is, to our knowledge, the first sequence editing software designed for both rRNA- and protein-coding genes with the visualization of biologically relevant information and should be useful in molecular phylogenetic studies. EzEditor is based on Java, can be run on all major computer operating systems and is freely available from http://sw.ezbiocloud.net/ezeditor/.

  5. Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency.

    PubMed

    El-Khairi, Ranna; Parnaik, Rahul; Duncan, Andrew J; Lin, Lin; Gerrelli, Dianne; Dattani, Mehul T; Conway, Gerard S; Achermann, John C

    2012-04-04

    Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency

    PubMed Central

    El-Khairi, Ranna; Parnaik, Rahul; Duncan, Andrew J.; Lin, Lin; Gerrelli, Dianne; Dattani, Mehul T.; Conway, Gerard S.; Achermann, John C.

    2012-01-01

    Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9 weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI. PMID:22240064

  7. Lin28 Induces Resistance to Anti-Androgens Via Promotion of AR Splice Variant Generation

    PubMed Central

    Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Evans, Christopher P.; Gao, Allen C.

    2017-01-01

    BACKGROUND Prostate cancer (PCa) is androgen-dependent initially and progresses to a castration-resistant state after androgen deprivation therapy. Treatment options for castration-resistant PCa include the potent second-generation anti-androgen enzalutamide or CYP17A1 inhibitor abiraterone. Recent clinical observations point to the development of resistance to these therapies which may be mediated by constitutively active alternative splice variants of the androgen receptor (AR). METHODS Sensitivity of LNCaP cells overexpressing Lin28 (LN-Lin28) to enzalutamide, abiraterone, or bicalutamide was compared to that of control LN-neo cells using cell growth assays, proliferation assays using MTT, anchorage-dependent clonogenic ability assays and soft agar assays. Ability of LN-Lin28 cells to maintain AR activation after treatment with enzalutamide, abiraterone, or bicalutamide was tested using immunofluorescence, Western blotting, ChIP assays, and qRT-PCR. Importance of Lin28 in enzalutamide resistance was assessed by the downregulation of Lin28 expression in C4-2B and 22Rv1 cells chronically treated with enzalutamide. Requirement for sustained AR signaling in LN-Lin28 cells was examined by the downregulation of either full length AR or AR-V7 using siRNA. RESULTS We show that Lin28 promotes the development of resistance to currently used targeted therapeutics by enhancing the expression of AR splice variants such as AR-V7. PCa cells overexpressing Lin28 exhibit resistance to treatment with enzalutamide, abiraterone, or bicalutamide. Downregulation of Lin28 resensitizes enzalutamide-resistant PCa cells to enzalutamide treatment. We also show that the upregulation of splicing factors such as hnRNPA1 by Lin28 may mediate the enhanced generation of AR splice variants in Lin28-expressing cells. CONCLUSIONS Our findings suggest that Lin28 plays a key role in the acquisition of resistance to AR-targeted therapies by PCa cells and establish the importance of Lin28 in PCa

  8. Lin28 induces resistance to anti-androgens via promotion of AR splice variant generation.

    PubMed

    Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Evans, Christopher P; Gao, Allen C

    2016-04-01

    Prostate cancer (PCa) is androgen-dependent initially and progresses to a castration-resistant state after androgen deprivation therapy. Treatment options for castration-resistant PCa include the potent second-generation anti-androgen enzalutamide or CYP17A1 inhibitor abiraterone. Recent clinical observations point to the development of resistance to these therapies which may be mediated by constitutively active alternative splice variants of the androgen receptor (AR). Sensitivity of LNCaP cells overexpressing Lin28 (LN-Lin28) to enzalutamide, abiraterone, or bicalutamide was compared to that of control LN-neo cells using cell growth assays, proliferation assays using MTT, anchorage-dependent clonogenic ability assays and soft agar assays. Ability of LN-Lin28 cells to maintain AR activation after treatment with enzalutamide, abiraterone, or bicalutamide was tested using immunofluorescence, Western blotting, ChIP assays, and qRT-PCR. Importance of Lin28 in enzalutamide resistance was assessed by the downregulation of Lin28 expression in C4-2B and 22Rv1 cells chronically treated with enzalutamide. Requirement for sustained AR signaling in LN-Lin28 cells was examined by the downregulation of either full length AR or AR-V7 using siRNA. We show that Lin28 promotes the development of resistance to currently used targeted therapeutics by enhancing the expression of AR splice variants such as AR-V7. PCa cells overexpressing Lin28 exhibit resistance to treatment with enzalutamide, abiraterone, or bicalutamide. Downregulation of Lin28 resensitizes enzalutamide-resistant PCa cells to enzalutamide treatment. We also show that the upregulation of splicing factors such as hnRNPA1 by Lin28 may mediate the enhanced generation of AR splice variants in Lin28-expressing cells. Our findings suggest that Lin28 plays a key role in the acquisition of resistance to AR-targeted therapies by PCa cells and establish the importance of Lin28 in PCa progression. © 2015 Wiley Periodicals, Inc.

  9. EDITORIAL: Incoming Editor-in-Chief Incoming Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Birch, David

    2012-01-01

    It is a pleasure and an honour for me to be taking over as Editor-in-Chief of Measurement Science and Technology. MST is well known across research communities worldwide as a leading journal in which to publish new techniques and instrumentation. It has gained this enviable position largely because of the excellent guidance of its Editorial Board and dedicated staff at Institute of Physics Publishing over many years. I want to highlight in particular the contribution of the outgoing Editor Peter Hauptmann, and other Editors before him, in making the journal truly international. We thank Peter immensely for all his hard work in leading the journal, having exceptionally served two terms, each of five years. I come into the post of Editor at a very interesting and challenging time for research. The global recession is leading to cuts in research funding in many countries, researchers and their outputs are coming under closer scrutiny than ever before, and more is being expected of them. Journals play a critical role in monitoring and maintaining research standards, but we should be careful not to assume that journal Impact Factor is the sole measure of research quality. Although expediency may sometimes demand it, Impact Factor, as practitioners know, is subject dependent. One of the great things about science and technology for me is its level playing field. The key point is still innovation no matter where the work is done or where it is published. MST has a long pedigree of being the natural home of the highest quality papers from leading researchers wishing to report novel instrumentation and techniques. 2013 will mark the 90th anniversary of MST and we look forward to celebrating in style its sustained success. I recall with pride the first paper I published in Journal of Physics E: Scientific Instruments (as MST was previously titled) back in 1977. The paper reported the design and application of an early fluorescence lifetime spectrometer that I had constructed

  10. Bacterial diversity and real-time PCR based assessment of linA and linB gene distribution at hexachlorocyclohexane contaminated sites.

    PubMed

    Lal, Devi; Jindal, Swati; Kumari, Hansi; Jit, Simran; Nigam, Aeshna; Sharma, Pooja; Kumari, Kirti; Lal, Rup

    2015-03-01

    The disposal of hexachlorocyclohexane (HCH) muck has created large number of HCH dumpsites all over the world from where the harmful HCH isomers are leaking into the environment. Bacteria have evolved at such contaminated sites that have the ability to degrade HCH. Degradation of various HCH isomers in bacterial strains is mediated primarily by two genes: linA and linB which encode dehydrochlorinase and haloalkane dehalogenase respectively. In this study we explored one such highly contaminated HCH dumpsite located in Lucknow, Uttar Pradesh, India. To assess the biostimulation potential of the contaminated site, microbial diversity study and real-time PCR based quantification of lin genes was carried out. The soil samples from dumpsite and surrounding areas were found to be highly contaminated with HCH residue levels as high as 1.8 × 10(5)  mg kg(-1). The residues were detected in areas upto 13 km from the dumpsite. Sphingomonads, Chromohalobacter, and Marinobacter were the dominant genera present at the dump-site. Role of Sphingomonads in HCH degradation has been well documented. The highest copy numbers of linA and linB genes as determined using real-time PCR were 6.2 × 10(4) and 5.3 × 10(5), respectively, were found in sample from the dump site. The presence of Sphingomonads, linA, and linB genes from HCH contaminated soil indicates the presence of indigenous bacterial communities capable of HCH degradation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Identification of MicroRNAs Regulating Reprogramming Factor LIN28 in Embryonic Stem Cells and Cancer Cells*

    PubMed Central

    Zhong, Xiaomin; Li, Ning; Liang, Shun; Huang, Qihong; Coukos, George; Zhang, Lin

    2010-01-01

    LIN28 (a homologue of the Caenorhabditis elegans lin-28 gene) is an evolutionarily conserved RNA-binding protein and a master regulator controlling the pluripotency of embryonic stem cells. Together with OCT4, SOX2, and NANOG, LIN28 can reprogram somatic cells, producing induced pluripotent stem cells. Expression of LIN28 is highly restricted to embryonic stem cells and developing tissues. In human tumors, LIN28 is up-regulated and functions as an oncogene promoting malignant transformation and tumor progression. However, the mechanisms of transcriptional and post-transcriptional regulation of LIN28 are still largely unknown. To examine microRNAs (miRNAs) that repress LIN28 expression, a combined in silico prediction and miRNA library screening approach was used in the present study. Four miRNAs directly regulating LIN28 (let-7, mir-125, mir-9, and mir-30) were initially identified by this approach and further validated by quantitative RT-PCR, Western blot analysis, and a LIN28 3′-UTR reporter assay. We found that expression levels of these four miRNAs were clustered together and inversely correlated with LIN28 expression during embryonic stem cell differentiation. In addition, the expression of these miRNAs was remarkably lower in LIN28-positive tumor cells compared with LIN28-negative tumor cells. Importantly, we demonstrated that these miRNAs were able to regulate the expression and activity of let-7, mediated by LIN28. Taken together, our studies demonstrate that miRNAs let-7, mir-125, mir-9, and mir-30 directly repress LIN28 expression in embryonic stem and cancer cells. Global down-regulation of these miRNAs may be one of the mechanisms of LIN28 reactivation in human cancers. PMID:20947512

  12. Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells.

    PubMed

    Zhong, Xiaomin; Li, Ning; Liang, Shun; Huang, Qihong; Coukos, George; Zhang, Lin

    2010-12-31

    LIN28 (a homologue of the Caenorhabditis elegans lin-28 gene) is an evolutionarily conserved RNA-binding protein and a master regulator controlling the pluripotency of embryonic stem cells. Together with OCT4, SOX2, and NANOG, LIN28 can reprogram somatic cells, producing induced pluripotent stem cells. Expression of LIN28 is highly restricted to embryonic stem cells and developing tissues. In human tumors, LIN28 is up-regulated and functions as an oncogene promoting malignant transformation and tumor progression. However, the mechanisms of transcriptional and post-transcriptional regulation of LIN28 are still largely unknown. To examine microRNAs (miRNAs) that repress LIN28 expression, a combined in silico prediction and miRNA library screening approach was used in the present study. Four miRNAs directly regulating LIN28 (let-7, mir-125, mir-9, and mir-30) were initially identified by this approach and further validated by quantitative RT-PCR, Western blot analysis, and a LIN28 3'-UTR reporter assay. We found that expression levels of these four miRNAs were clustered together and inversely correlated with LIN28 expression during embryonic stem cell differentiation. In addition, the expression of these miRNAs was remarkably lower in LIN28-positive tumor cells compared with LIN28-negative tumor cells. Importantly, we demonstrated that these miRNAs were able to regulate the expression and activity of let-7, mediated by LIN28. Taken together, our studies demonstrate that miRNAs let-7, mir-125, mir-9, and mir-30 directly repress LIN28 expression in embryonic stem and cancer cells. Global down-regulation of these miRNAs may be one of the mechanisms of LIN28 reactivation in human cancers.

  13. LIN28A is a suppressor of ER-associated translation in embryonic stem cells.

    PubMed

    Cho, Jun; Chang, Hyeshik; Kwon, S Chul; Kim, Baekgyu; Kim, Yoosik; Choe, Junho; Ha, Minju; Kim, Yoon Ki; Kim, V Narry

    2012-11-09

    LIN28 plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, LIN28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. In this study, we obtain a genome-wide view of the molecular function of LIN28A in mouse embryonic stem cells by carrying out RNA crosslinking-immunoprecipitation-sequencing (CLIP-seq) and ribosome footprinting. We find that, in addition to let-7 precursors, LIN28A binds to a large number of spliced mRNAs. LIN28A recognizes AAGNNG, AAGNG, and less frequently UGUG, which are located in the terminal loop of a small hairpin. LIN28A is localized to the periendoplasmic reticulum (ER) area and inhibits translation of mRNAs that are destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Our study suggests a selective regulatory mechanism for ER-associated translation and reveals an unexpected role of LIN28A as a global suppressor of genes in the secretory pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies.

    PubMed

    Zhu, Hao; Shah, Samar; Shyh-Chang, Ng; Shinoda, Gen; Einhorn, William S; Viswanathan, Srinivas R; Takeuchi, Ayumu; Grasemann, Corinna; Rinn, John L; Lopez, Mary F; Hirschhorn, Joel N; Palmert, Mark R; Daley, George Q

    2010-07-01

    Recently, genome-wide association studies have implicated the human LIN28B locus in regulating height and the timing of menarche. LIN28B and its homolog LIN28A are functionally redundant RNA-binding proteins that block biogenesis of let-7 microRNAs. lin-28 and let-7 were discovered in Caenorhabditis elegans as heterochronic regulators of larval and vulval development but have recently been implicated in cancer, stem cell aging and pluripotency. The let-7 targets Myc, Kras, Igf2bp1 and Hmga2 are known regulators of mammalian body size and metabolism. To explore the function of the Lin28-Let-7 pathway in vivo, we engineered transgenic mice to express Lin28a and observed in them increased body size, crown-rump length and delayed onset of puberty. Investigation of metabolic and endocrine mechanisms of overgrowth in these transgenic mice revealed increased glucose metabolism and insulin sensitivity. Here we report a mouse that models the human phenotypes associated with genetic variation in the Lin28-Let-7 pathway.

  15. LIN28: A Stem Cell Factor with a Key Role in Pediatric Tumor Formation.

    PubMed

    Carmel-Gross, Ilana; Bollag, Naomi; Armon, Leah; Urbach, Achia

    2016-03-01

    Differentiation and development are normally unidirectional processes in which progenitor/stem cells differentiate into more mature cells. Transformation of adult cells into cancer cells is accompanied in many cases by dedifferentiation of the adult cell, while differentiation failure of progenitor cells can result in the formation of unique type of cancers called pediatric cancer. LIN28A and its paralog LIN28B are pluripotent genes that are expressed mainly in stem/progenitor cells. Since the first identification of LIN28 in mammals, numerous studies demonstrated the general oncogenic features of these genes. In this review, we emphasize the unique role of LIN28 in pediatric tumor formation. We show, based on comprehensive literature screen and analysis of published microarray data, that LIN28 expression in pediatric tumors is even more common than in adult tumors, and discuss the possibility that in the case of pediatric cancers, LIN28 acts by preventing normal development/differentiation rather than by transformation of mature cells into cancer cells. Overall, this review highlights the role of LIN28 as a bridge point between embryonic development, stem cell biology, and cancer.

  16. The relationship between Lin28 and the chemotherapy response of gastric cancer.

    PubMed

    Teng, Rong Yue; Zhou, Ji Chun; Jiang, Zi Nong; Xu, Chao Yang; Li, Zi Duo; Wang, Qing Chuan; Xu, Chen Pu; Guo, Ju Feng; Shen, Jian Guo; Wang, Lin Bo

    2013-01-01

    The aim of the study reported here was to identify whether a stem cell biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. The study enrolled 47 patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue was biopsied by gastroscopy and Lin28 expression in the tissue was measured by immunohistochemistry. Statistical analyses were performed to identify the relationship between Lin28 expression and tumor regression grade. Of the 47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic response in 18 (38.3%). Receiver-operating characteristic curve analysis showed that the histoscore of Lin28 expression with 0.325 as a cutoff value could differentiate between pathologic response and nonresponse. Multivariable analysis showed that Lin28 expression was an independent predictive factor for pathologic response to neoadjuvant chemotherapy (P = 0.006). Lin28 expression was associated with pathologic tumor response in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can serve as a predictive biomarker for neoadjuvant chemotherapy in patients with gastric cancer.

  17. The Lin28 cold-shock domain remodels pre-let-7 microRNA.

    PubMed

    Mayr, Florian; Schütz, Anja; Döge, Nadine; Heinemann, Udo

    2012-08-01

    The RNA-binding protein Lin28 regulates the processing of a developmentally important group of microRNAs, the let-7 family. Lin28 blocks the biogenesis of let-7 in embryonic stem cells and thereby prevents differentiation. It was shown that both RNA-binding domains (RBDs) of this protein, the cold-shock domain (CSD) and the zinc-knuckle domain (ZKD) are indispensable for pri- or pre-let-7 binding and blocking its maturation. Here, we systematically examined the nucleic acid-binding preferences of the Lin28 RBDs and determined the crystal structure of the Lin28 CSD in the absence and presence of nucleic acids. Both RNA-binding domains bind to single-stranded nucleic acids with the ZKD mediating specific binding to a conserved GGAG motif and the CSD showing only limited sequence specificity. However, only the isolated Lin28 CSD, but not the ZKD, can bind with a reasonable affinity to pre-let-7 and thus is able to remodel the terminal loop of pre-let-7 including the Dicer cleavage site. Further mutagenesis studies reveal that the Lin28 CSD induces a conformational change in the terminal loop of pre-let-7 and thereby facilitates a subsequent specific binding of the Lin28 ZKD to the conserved GGAG motif.

  18. Determinants of mRNA recognition and translation regulation by Lin28.

    PubMed

    Lei, Xin-Xiang; Xu, Jie; Ma, Wei; Qiao, Chong; Newman, Martin A; Hammond, Scott M; Huang, Yingqun

    2012-04-01

    Lin28 is critical for stem cell maintenance and is also associated with advanced human malignancies. Our recent genome-wide studies mark Lin28 as a master post-transcriptional regulator of a subset of messenger RNAs important for cell growth and metabolism. However, the molecular basis underpinning the selective mRNA target regulation is unclear. Here, we provide evidence that Lin28 recognizes a unique motif in multiple target mRNAs, characterized by a small but critical 'A' bulge flanked by two G:C base pairs embedded in a complex secondary structure. This motif mediates Lin28-dependent stimulation of translation. As Lin28 is also known to inhibit the biogenesis of a cohort of miRNAs including let-7, we propose that Lin28 binding to different RNA types (precursor miRNAs versus mRNAs) may facilitate recruitment of different co-factors, leading to distinct regulatory outcomes. Our findings uncover a putative yet unexpected motif that may constitute a mechanistic base for the multitude of functions regulated by Lin28 in both stem cells and cancer cells.

  19. Lin28: an emerging important oncogene connecting several aspects of cancer.

    PubMed

    Wang, Hao; Zhao, Qin; Deng, Kaiyuan; Guo, Xiaoqiang; Xia, Jiazeng

    2016-03-01

    RNA-binding protein Lin28 was originally found as a heterochronic gene which played a significant role in the development of Caenorhabditis elegans. The tumor suppressor let-7 is a downstream target of Lin28, which has a wide variety of target genes which are involved in many aspects of cellular activities. By inhibition of let-7 and directly binding the target RNAs, Lin28 plays an important role in different biological and pathological processes including differentiation, metabolism, proliferation, pluripotency, and tumorigenesis. Overexpression of Lin28 has been reported in several kinds of cancers and is correlated with poor outcomes. It has been shown that Lin28 could affect the progression of cancers in several ways, such as promoting proliferation, increasing glucose metabolism, and inducing epithelial-mesenchymal transition (EMT) and cancer stem cells. Decrease of Lin28 expression or reactivation of let-7 in cancer cells could induce a reverse effect, indicating their therapeutic values in developing novel strategies for cancer treatment. Here, we will overview the regulatory mechanisms and functions of Lin28 in cancers.

  20. Lin28 and let-7: roles and regulation in liver diseases

    PubMed Central

    McDaniel, Kelly; Hall, Chad; Sato, Keisaku; Lairmore, Terry; Marzioni, Marco; Glaser, Shannon; Meng, Fanyin

    2016-01-01

    The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell marker vital to initiation or maintenance of a stem cell phenotype. Lin28 has not been extensively studied in the liver, despite its ability to induce tissue regeneration via reprogramming of oxidative enzymes in other tissues and its involvement with numerous upstream regulators and downstream targets in liver disease. Theoretically, overexpression of Lin28 in certain forms of liver disease could be a potential treatment that aids in liver regeneration. Alternatively, Lin28 has been implicated numerous times in the progression of diverse cancer types and is associated with increased severity of disease. In this case, Lin28 could be a potential inhibitory target to prevent malignant transformation in the liver. This review seeks to characterize the role of Lin28 in liver disease. PMID:27012771

  1. The Lin28 cold-shock domain remodels pre-let-7 microRNA

    PubMed Central

    Mayr, Florian; Schütz, Anja; Döge, Nadine; Heinemann, Udo

    2012-01-01

    The RNA-binding protein Lin28 regulates the processing of a developmentally important group of microRNAs, the let-7 family. Lin28 blocks the biogenesis of let-7 in embryonic stem cells and thereby prevents differentiation. It was shown that both RNA-binding domains (RBDs) of this protein, the cold-shock domain (CSD) and the zinc-knuckle domain (ZKD) are indispensable for pri- or pre-let-7 binding and blocking its maturation. Here, we systematically examined the nucleic acid-binding preferences of the Lin28 RBDs and determined the crystal structure of the Lin28 CSD in the absence and presence of nucleic acids. Both RNA-binding domains bind to single-stranded nucleic acids with the ZKD mediating specific binding to a conserved GGAG motif and the CSD showing only limited sequence specificity. However, only the isolated Lin28 CSD, but not the ZKD, can bind with a reasonable affinity to pre-let-7 and thus is able to remodel the terminal loop of pre-let-7 including the Dicer cleavage site. Further mutagenesis studies reveal that the Lin28 CSD induces a conformational change in the terminal loop of pre-let-7 and thereby facilitates a subsequent specific binding of the Lin28 ZKD to the conserved GGAG motif. PMID:22570413

  2. Lin28 and let-7: roles and regulation in liver diseases.

    PubMed

    McDaniel, Kelly; Hall, Chad; Sato, Keisaku; Lairmore, Terry; Marzioni, Marco; Glaser, Shannon; Meng, Fanyin; Alpini, Gianfranco

    2016-05-15

    The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell marker vital to initiation or maintenance of a stem cell phenotype. Lin28 has not been extensively studied in the liver, despite its ability to induce tissue regeneration via reprogramming of oxidative enzymes in other tissues and its involvement with numerous upstream regulators and downstream targets in liver disease. Theoretically, overexpression of Lin28 in certain forms of liver disease could be a potential treatment that aids in liver regeneration. Alternatively, Lin28 has been implicated numerous times in the progression of diverse cancer types and is associated with increased severity of disease. In this case, Lin28 could be a potential inhibitory target to prevent malignant transformation in the liver. This review seeks to characterize the role of Lin28 in liver disease.

  3. The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy

    PubMed Central

    Wang, Leo D.; Rao, Tata Nageswara; Rowe, R. Grant; Nguyen, Phi T.; Sullivan, Jessica L.; Pearson, Daniel S.; Doulatov, Sergei; Wu, Linwei; Lindsley, R. Coleman; Zhu, Hao; DeAngelo, Daniel J.; Daley, George Q.; Wagers, Amy J.

    2015-01-01

    Mast cells are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration, and tumor progression. Dysregulated mast cell development leads to systemic mastocytosis, a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused mast cell accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-mast cell progenitors altering gene expression patterns to favor cell fate choices that enhanced mast cell specification. In addition, LIN28B-induced mast cells appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of mast cell terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human mast cell leukemia samples revealed upregulation of LIN28B in abnormal mast cells from patients with systemic mastocytosis (SM). This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in mast cell disease. PMID:25655194

  4. Starving for more: Nutrient sensing by LIN-28 in adult intestinal progenitor cells.

    PubMed

    Luhur, Arthur; Sokol, Nicholas

    2015-01-01

    In this Extra View, we extend our recent work on the protein LIN-28 and its role in adult stem cell divisions. LIN-28 is an mRNA- and microRNA-binding protein that is conserved from worms to humans. When expressed ectopically, it promotes the reprogramming of differentiated vertebrate cells into pluripotent stem cells as well as the regeneration of vertebrate tissues after injury. However, its endogenous function in stem cell populations is less clear. We recently reported that LIN-28 is specifically expressed in progenitor cells in the adult Drosophila intestine and enhances insulin signaling within this population. Loss of lin-28 alters the division patterns of these progenitor cells, limiting the growth of the intestinal epithelium that is ordinarily caused by feeding. Thus, LIN-28 is part of an uncharacterized circuit used to remodel a tissue in response to environmental cues like nutrition. Here, we extend this analysis by reporting that the levels of LIN-28 in progenitor cells are sensitive to nutrient availability. In addition, we speculate about the role of LIN-28 in the translational control of target mRNAs such as Insulin Receptor (InR) and how such translational control may be an important mechanism that underlies the stem cell dynamics needed for tissue homeostasis and growth.

  5. The C. elegans hox gene lin-39 controls cell cycle progression during vulval development.

    PubMed

    Roiz, Daniel; Escobar-Restrepo, Juan Miguel; Leu, Philipp; Hajnal, Alex

    2016-10-01

    Cell fate specification during organogenesis is usually followed by a phase of cell proliferation to produce the required number of differentiated cells. The Caenorhabditis elegans vulva is an excellent model to study how cell fate specification and cell proliferation are coordinated. The six vulval precursor cells (VPCs) are born at the first larval stage, but they arrest in the G1 phase of the cell cycle until the beginning of the third larval stage, when their fates are specified and the three proximal VPCs proliferate to generate 22 vulval cells. An epidermal growth factor (EGF) signal from the gonadal anchor cell combined with lateral DELTA/NOTCH signaling between the VPCs determine the primary (1°) and secondary (2°) fates, respectively. The hox gene lin-39 plays a key role in integrating these spatial patterning signals and in maintaining the VPCs as polarized epithelial cells. Using a fusion-defective eff-1(lf) mutation to keep the VPCs polarized, we find that VPCs lacking lin-39 can neither activate lateral NOTCH signaling nor proliferate. LIN-39 promotes cell cycle progression through two distinct mechanisms. First, LIN-39 maintains the VPCs competent to proliferate by inducing cdk-4 cdk and cye-1 cyclinE expression via a non-canonical HOX binding motif. Second, LIN-39 activates in the adjacent VPCs the NOTCH signaling pathway, which promotes VPC proliferation independently of LIN-39. The hox gene lin-39 is therefore a central node in a regulatory network coordinating VPC differentiation and proliferation.

  6. The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.

    PubMed

    Faunes, Fernando; Gundermann, Daniel G; Muñoz, Rosana; Bruno, Renzo; Larraín, Juan

    2017-05-15

    Metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. It has been very well established that amphibian metamorphosis is mainly controlled by Thyroid Hormone (TH). Here, we show that the heterochronic gene Lin28 is downregulated during Xenopus laevis metamorphosis. Lin28 overexpression before activation of TH signaling delays metamorphosis and inhibits the expression of TH target genes. The delay in metamorphosis is rescued by incubation with exogenous TH, indicating that Lin28 works upstream or parallel to TH. High-throughput analyses performed before any delay on metamorphosis or change in TH signaling showed that overexpression of Lin28 reduces transcript levels of several hormones secreted by the pituitary, including the Thyroid-Stimulating Hormone (TSH), and regulates the expression of proteins involved in TH transport, metabolism and signaling, showing that Lin28 disrupts TH function at different levels. Our data demonstrates that the role of Lin28 in controlling developmental transitions is evolutionary conserved and establishes a functional interaction between Lin28 and thyroid hormone function introducing a new regulatory step in perinatal development with implications for our understanding of endocrine disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells

    PubMed Central

    Yang, Jun; Bennett, Brian D.; Luo, Shujun; Inoue, Kaoru; Grimm, Sara A.; Schroth, Gary P.; Bushel, Pierre R.

    2015-01-01

    LIN28 is an evolutionarily conserved RNA-binding protein with critical functions in developmental timing and cancer. However, the molecular mechanisms underlying LIN28's oncogenic properties are yet to be described. RNA-protein immunoprecipitation coupled with genome-wide sequencing (RIP-Seq) analysis revealed significant LIN28 binding within 843 mRNAs in breast cancer cells. Many of the LIN28-bound mRNAs are implicated in the regulation of RNA and cell metabolism. We identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein with multiple roles in mRNA metabolism, as a LIN28-interacting partner. Subsequently, we used a custom computational method to identify differentially spliced gene isoforms in LIN28 and hnRNP A1 small interfering RNA (siRNA)-treated cells. The results reveal that these proteins regulate alternative splicing and steady-state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of the ENAH exon 11a isoform. The expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Intriguingly, analysis of publicly available array data from the Cancer Genome Atlas (TCGA) reveals that LIN28 expression in the HER2 subtype is significantly different from that in other breast cancer subtypes. Collectively, our data suggest that LIN28 may regulate splicing and gene expression programs that drive breast cancer subtype phenotypes. PMID:26149387

  8. RNA-binding protein LIN28 is a sensitive marker of pediatric yolk sac tumors.

    PubMed

    Feng, Shaoguang; Huang, Songsong; Tong, Yulong; Chen, Zhongliang; Shen, Delei; Wu, Dazhou; Lai, Xin-He; Chen, Xiaoming

    2016-08-01

    RNA-binding protein LIN28 is involved in maintaining the pluripotency of embryonic stem cells. It has been detected in different types of testicular and ovarian germ cell tumors (GCTs), but its status in pediatric YSTs (yolk sac tumors) is still unknown. The aim of this study was to determine the immunohistochemical profile of LIN28 in pediatric YSTs. Immunohistochemistry detection of LIN28 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30 % cells), 2+ (31-60 %), 3+ (61-90 %), and 4+ (>90 %). To compare its sensitive and specificity with alpha-fetoprotein (AFP), we also stained AFP in 22 cases of pediatric YSTs and 10 mature teratomas in children. LIN28 staining was high in all 22 pediatric yolk sac tumor (2+ in 1, 3+ in 1, and 4+ in 20), and weak staining of LIN28 was seen in 1 of 10 mature teratomas (1+), 9 of 10 mature teratomas were negative expression. However, the expression of AFP in pediatric YST was lower compared with Lin28 (- in 1, 1+ in 8, 2+ in 12, and 3+ in 1), and weak expression of AFP was seen in 2 of 10 mature teratomas (1+), 8 of 10 mature teratomas were negative. LIN28 had higher intensity expression than AFP in pediatric YSTs (P < 0.001). LIN28 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. LIN28 is likely to become a new and valuable biomarker for diagnosing of pediatric YST.

  9. Lin28 is induced in primed embryonic stem cells and regulates let-7-independent events.

    PubMed

    Parisi, Silvia; Passaro, Fabiana; Russo, Luigi; Musto, Anna; Navarra, Angelica; Romano, Simona; Petrosino, Giuseppe; Russo, Tommaso

    2017-03-01

    Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci. These mechanisms are crucial for Lin28 regulation, as demonstrated by the abolishment of the Lin28 accumulation in Otx2- or Hmga2-knockout cells compared to the control cells. We have also found that Lin28 controls Hmga2 expression levels during ESC differentiation through a let-7-independent mechanism. Indeed, we found that Lin28 proteins bind a highly conserved element in the 3' UTR of Hmga2 mRNA, and this provokes a down-regulation of its translation. This mechanism prevents the inappropriate accumulation of Hmga2 that would modify the proliferation and physiological apoptosis of differentiating ESCs. In summary, we demonstrated that during ESC differentiation, Lin28 transient induction is dependent on Otx2 and Hmga2 and prevents an inappropriate excessive rise of Hmga2 levels.-Parisi, S., Passaro, F., Russo, L., Musto, A., Navarra, A., Romano, S., Petrosino, G., Russo, T. Lin28 is induced in primed embryonic stem cells and regulates let-7-independent events. © FASEB.

  10. The pluripotency factor LIN28 in monkey and human testes: a marker for spermatogonial stem cells?

    PubMed

    Aeckerle, N; Eildermann, K; Drummer, C; Ehmcke, J; Schweyer, S; Lerchl, A; Bergmann, M; Kliesch, S; Gromoll, J; Schlatt, S; Behr, R

    2012-10-01

    Mammalian spermatogenesis is maintained by spermatogonial stem cells (SSCs). However, since evidentiary assays and unequivocal markers are still missing in non-human primates (NHPs) and man, the identity of primate SSCs is unknown. In contrast, in mice, germ cell transplantation studies have functionally demonstrated the presence of SSCs. LIN28 is an RNA-binding pluripotent stem cell factor, which is also strongly expressed in undifferentiated mouse spermatogonia. By contrast, two recent reports indicated that LIN28 is completely absent from adult human testes. Here, we analyzed LIN28 expression in marmoset monkey (Callithrix jacchus) and human testes during development and adulthood and compared it with that in mice. In the marmoset, LIN28 was strongly expressed in migratory primordial germ cells and gonocytes. Strikingly, we found a rare LIN28-positive subpopulation of spermatogonia also in adult marmoset testis. This was corroborated by western blotting and quantitative RT-PCR. Importantly, in contrast to previous publications, we found LIN28-positive spermatogonia also in normal adult human and additional adult NHP testes. Some seasonal breeders exhibit a degenerated (involuted) germinal epithelium consisting only of Sertoli cells and SSCs during their non-breeding season. The latter re-initiate spermatogenesis prior to the next breeding-season. Fully involuted testes from a seasonal hamster and NHP (Lemur catta) exhibited numerous LIN28-positive spermatogonia, indicating an SSC identity of the labeled cells. We conclude that LIN28 is differentially expressed in mouse and NHP spermatogonia and might be a marker for a rare SSC population in NHPs and man. Further characterization of the LIN28-positive population is required.

  11. The pluripotency factor LIN28 in monkey and human testes: a marker for spermatogonial stem cells?

    PubMed Central

    Aeckerle, N.; Eildermann, K.; Drummer, C.; Ehmcke, J.; Schweyer, S.; Lerchl, A.; Bergmann, M.; Kliesch, S.; Gromoll, J.; Schlatt, S.; Behr, R.

    2012-01-01

    Mammalian spermatogenesis is maintained by spermatogonial stem cells (SSCs). However, since evidentiary assays and unequivocal markers are still missing in non-human primates (NHPs) and man, the identity of primate SSCs is unknown. In contrast, in mice, germ cell transplantation studies have functionally demonstrated the presence of SSCs. LIN28 is an RNA-binding pluripotent stem cell factor, which is also strongly expressed in undifferentiated mouse spermatogonia. By contrast, two recent reports indicated that LIN28 is completely absent from adult human testes. Here, we analyzed LIN28 expression in marmoset monkey (Callithrix jacchus) and human testes during development and adulthood and compared it with that in mice. In the marmoset, LIN28 was strongly expressed in migratory primordial germ cells and gonocytes. Strikingly, we found a rare LIN28-positive subpopulation of spermatogonia also in adult marmoset testis. This was corroborated by western blotting and quantitative RT–PCR. Importantly, in contrast to previous publications, we found LIN28-positive spermatogonia also in normal adult human and additional adult NHP testes. Some seasonal breeders exhibit a degenerated (involuted) germinal epithelium consisting only of Sertoli cells and SSCs during their non-breeding season. The latter re-initiate spermatogenesis prior to the next breeding-season. Fully involuted testes from a seasonal hamster and NHP (Lemur catta) exhibited numerous LIN28-positive spermatogonia, indicating an SSC identity of the labeled cells. We conclude that LIN28 is differentially expressed in mouse and NHP spermatogonia and might be a marker for a rare SSC population in NHPs and man. Further characterization of the LIN28-positive population is required. PMID:22689537

  12. The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans

    PubMed Central

    Van Wynsberghe, Priscilla M.; Finnegan, Emily F.; Stark, Thomas; Angelus, Evan P.; Homan, Kathryn E.; Yeo, Gene W.; Pasquinelli, Amy E.

    2014-01-01

    MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate the appropriate amount of a particular miRNA in the correct location at the correct time, proper regulation of miRNA biogenesis is essential. Here we identify the Period protein homolog LIN-42 as a new regulator of miRNA biogenesis in Caenorhabditis elegans. We mapped a spontaneous suppressor of the normally lethal let-7(n2853) allele to the lin-42 gene. Mutations in this allele (ap201) or a second lin-42 allele (n1089) caused increased mature let-7 miRNA levels at most time points when mature let-7 miRNA is normally expressed. Levels of pri-let-7 and a let-7 transcriptional reporter were also increased in lin-42(n1089) worms. These results indicate that LIN-42 normally represses pri-let-7 transcription and thus the accumulation of let-7 miRNA. This inhibition is not specific to let-7, as pri- and mature levels of lin-4 and miR-35 were also increased in lin-42 mutants. Furthermore, small RNA-seq analysis showed widespread increases in the levels of mature miRNAs in lin-42 mutants. Thus, we propose that the period protein homolog LIN-42 is a global regulator of miRNA biogenesis. PMID:24699545

  13. The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans.

    PubMed

    Van Wynsberghe, Priscilla M; Finnegan, Emily F; Stark, Thomas; Angelus, Evan P; Homan, Kathryn E; Yeo, Gene W; Pasquinelli, Amy E

    2014-06-15

    MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate the appropriate amount of a particular miRNA in the correct location at the correct time, proper regulation of miRNA biogenesis is essential. Here we identify the Period protein homolog LIN-42 as a new regulator of miRNA biogenesis in Caenorhabditis elegans. We mapped a spontaneous suppressor of the normally lethal let-7(n2853) allele to the lin-42 gene. Mutations in this allele (ap201) or a second lin-42 allele (n1089) caused increased mature let-7 miRNA levels at most time points when mature let-7 miRNA is normally expressed. Levels of pri-let-7 and a let-7 transcriptional reporter were also increased in lin-42(n1089) worms. These results indicate that LIN-42 normally represses pri-let-7 transcription and thus the accumulation of let-7 miRNA. This inhibition is not specific to let-7, as pri- and mature levels of lin-4 and miR-35 were also increased in lin-42 mutants. Furthermore, small RNA-seq analysis showed widespread increases in the levels of mature miRNAs in lin-42 mutants. Thus, we propose that the period protein homolog LIN-42 is a global regulator of miRNA biogenesis.

  14. LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells.

    PubMed

    Yang, Jun; Bennett, Brian D; Luo, Shujun; Inoue, Kaoru; Grimm, Sara A; Schroth, Gary P; Bushel, Pierre R; Kinyamu, H Karimi; Archer, Trevor K

    2015-09-01

    LIN28 is an evolutionarily conserved RNA-binding protein with critical functions in developmental timing and cancer. However, the molecular mechanisms underlying LIN28's oncogenic properties are yet to be described. RNA-protein immunoprecipitation coupled with genome-wide sequencing (RIP-Seq) analysis revealed significant LIN28 binding within 843 mRNAs in breast cancer cells. Many of the LIN28-bound mRNAs are implicated in the regulation of RNA and cell metabolism. We identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein with multiple roles in mRNA metabolism, as a LIN28-interacting partner. Subsequently, we used a custom computational method to identify differentially spliced gene isoforms in LIN28 and hnRNP A1 small interfering RNA (siRNA)-treated cells. The results reveal that these proteins regulate alternative splicing and steady-state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of the ENAH exon 11a isoform. The expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Intriguingly, analysis of publicly available array data from the Cancer Genome Atlas (TCGA) reveals that LIN28 expression in the HER2 subtype is significantly different from that in other breast cancer subtypes. Collectively, our data suggest that LIN28 may regulate splicing and gene expression programs that drive breast cancer subtype phenotypes.

  15. An Update: 1976 and 1987 Editors' Predictions of Audience Reactions to Videotex and A Comparison: 1987 Audience Reactions and 1976 and 1987 Editors' Predictions.

    ERIC Educational Resources Information Center

    Davenport, Lucinda D.

    To discover if editors' perceptions of audience opinions had changed and to determine the accuracy of editors' predictions regarding readers' reactions to using videotex, a 1987 study repeated a 1976 survey of Associated Press managing editors, and compared the responses with the original survey results. Surveys were sent to 302 Associated Press…

  16. RNA-binding protein LIN28 is a marker for testicular germ cell tumors.

    PubMed

    Cao, Dengfeng; Allan, Robert W; Cheng, Liang; Peng, Yan; Guo, Charles C; Dahiya, Neha; Akhi, Shirin; Li, Jianping

    2011-05-01

    LIN28 is an RNA-binding protein involved in maintaining the pluripotency of embryonic stem cells. Using formalin-fixed, paraffin-embedded tissue blocks, we performed immunohistochemical staining of LIN28 in 103 primary and 81 metastatic testicular germ cell tumors (54 intratubular germ cell neoplasias, unclassified type; 49 primary and 20 metastatic classic seminomas; 35 primary and 24 metastatic embryonal carcinomas; 35 primary and 15 metastatic yolk sac tumors; 23 primary and 12 metastatic teratomas; 6 primary and 10 metastatic choriocarcinomas; and 5 spermatocytic seminomas). The percentage of tumor cell stained was scored as 0 (0%), 1+ (≤30%), 2+ (31%-60%), 3+ (61%-90%), and 4+ (>90%). We stained LIN28 in 327 non-germ cell tumors to determine its specificity. We also compared LIN28 with SALL4 (Sal-like 4) and OCT4 (octamer-binding transcription factor 4) in all germ cell tumors. The staining was cytoplasmic for LIN28 and nuclear for SALL4 and OCT4. Strong 4+ LIN28 staining was seen in all 54 intratubular germ cell neoplasias, 59 embryonal carcinomas, and 50 yolk sac tumors. Positive LIN28 staining was seen in all 69 classic seminomas (1+ in 3, 3+ in 3, and 4+ in 63) (63, strong). Variable staining of LIN28 was seen in 10 of 35 teratomas (1+ to 3+, weak to strong intensity), 12 of 16 choriocarcinomas (1+ to 4+, weak to strong intensity), and 1 of 5 spermatocytic seminomas (2+, weak). Only 10 of 327 non-germ cell tumors showed 1+ weak LIN28 staining. Therefore, LIN28 is a highly sensitive marker for testicular intratubular germ cell neoplasias, classic seminomas, embryonal carcinomas, and yolk sac tumors with relatively high specificity. LIN28 can be used as a diagnostic marker for these tumors and has demonstrated a similar level of diagnostic utility as SALL4 (except for a few classic seminomas), although it does not show an advantage over SALL4. The major advantage of LIN28 over OCT4 is in diagnosing yolk sac tumors (yolk sac tumors negative for OCT4

  17. LIN28 alters cell fate succession and acts independently of the let-7 microRNA during neurogliogenesis in vitro.

    PubMed

    Balzer, Erica; Heine, Christian; Jiang, Qiang; Lee, Vivian M; Moss, Eric G

    2010-03-01

    LIN28 is an RNA-binding protein that is expressed in many developing tissues. It can block let-7 (Mirlet7) microRNA processing and help promote pluripotency. We have observed LIN28 expression in the developing mouse neural tube, colocalizing with SOX2, suggesting a role in neural development. To better understand its normal developmental function, we investigated LIN28 activity during neurogliogenesis in vitro, where the succession of neuronal to glial cell fates occurs as it does in vivo. LIN28 expression was high in undifferentiated cells, and was downregulated rapidly upon differentiation. Constitutive LIN28 expression caused a complete block of gliogenesis and an increase in neurogenesis. LIN28 expression was compatible with neuronal differentiation and did not increase proliferation. LIN28 caused significant changes in gene expression prior to any effect on let-7, notably on Igf2. Furthermore, a mutant LIN28 that permitted let-7 accumulation was still able to completely block gliogenesis. Thus, at least two biological activities of LIN28 are genetically separable and might involve distinct mechanisms. LIN28 can differentially promote and inhibit specific fates and does not function exclusively by blocking let-7 family microRNAs. Importantly, the role of LIN28 in cell fate succession in vertebrate cells is analogous to its activity as a developmental timing regulator in C. elegans.

  18. Writing filter processes for the SAGA editor, appendix G

    NASA Technical Reports Server (NTRS)

    Kirslis, Peter A.

    1985-01-01

    The SAGA editor provides a mechanism by which separate processes can be invoked during an editing session to traverse portions of the parse tree being edited. These processes, termed filter processes, read, analyze, and possibly transform the parse tree, returning the result to the editor. By defining new commands with the editor's user defined command facility, which invoke filter processes, authors of filter can provide complex operations as simple commands. A tree plotter, pretty printer, and Pascal tree transformation program were already written using this facility. The filter processes are introduced, parse tree structure is described and the library interface made available to the programmer. Also discussed is how to compile and run filter processes. Examples are presented to illustrate aspect of each of these areas.

  19. SIRE: A Simple Interactive Rule Editor for NICBES

    NASA Technical Reports Server (NTRS)

    Bykat, Alex

    1988-01-01

    To support evolution of domain expertise, and its representation in an expert system knowledge base, a user-friendly rule base editor is mandatory. The Nickel Cadmium Battery Expert System (NICBES), a prototype of an expert system for the Hubble Space Telescope power storage management system, does not provide such an editor. In the following, a description of a Simple Interactive Rule Base Editor (SIRE) for NICBES is described. The SIRE provides a consistent internal representation of the NICBES knowledge base. It supports knowledge presentation and provides a user-friendly and code language independent medium for rule addition and modification. The SIRE is integrated with NICBES via an interface module. This module provides translation of the internal representation to Prolog-type rules (Horn clauses), latter rule assertion, and a simple mechanism for rule selection for its Prolog inference engine.

  20. JGR-Solid Earth and Planets editor Seth A. Stein

    NASA Astrophysics Data System (ADS)

    Katzoff, Judith A.

    Seth A. Stein, one of the editors of the Journal of Geophysical Research—Solid Earth and Planets, says that his approach to editing the journal is based on the premise that authors, reviewers, and editors are all drawn from the same community: the journal's readers. “We all want JGR to publish interesting papers of the highest possible quality. Each of us believes that the papers we review are improved by our comments. It follows, although it is a little harder for most of us to accept, that our own papers generally contain better science and are more useful to readers as a result of reviews,” Stein told Eos.Stein, an associate professor of geological sciences at Northwestern University (Evanston, Ill.), is one of the seven editors of JGR—Solid Earth and Planets for 1987 and 1988 (see box). His specialties are tectonophysics and seismology.

  1. Core competencies for scientific editors of biomedical journals: consensus statement.

    PubMed

    Moher, David; Galipeau, James; Alam, Sabina; Barbour, Virginia; Bartolomeos, Kidist; Baskin, Patricia; Bell-Syer, Sally; Cobey, Kelly D; Chan, Leighton; Clark, Jocalyn; Deeks, Jonathan; Flanagin, Annette; Garner, Paul; Glenny, Anne-Marie; Groves, Trish; Gurusamy, Kurinchi; Habibzadeh, Farrokh; Jewell-Thomas, Stefanie; Kelsall, Diane; Lapeña, José Florencio; MacLehose, Harriet; Marusic, Ana; McKenzie, Joanne E; Shah, Jay; Shamseer, Larissa; Straus, Sharon; Tugwell, Peter; Wager, Elizabeth; Winker, Margaret; Zhaori, Getu

    2017-09-11

    Scientific editors are responsible for deciding which articles to publish in their journals. However, we have not found documentation of their required knowledge, skills, and characteristics, or the existence of any formal core competencies for this role. We describe the development of a minimum set of core competencies for scientific editors of biomedical journals. The 14 key core competencies are divided into three major areas, and each competency has a list of associated elements or descriptions of more specific knowledge, skills, and characteristics that contribute to its fulfillment. We believe that these core competencies are a baseline of the knowledge, skills, and characteristics needed to perform competently the duties of a scientific editor at a biomedical journal.

  2. A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B.

    PubMed

    Suzuki, Hiroshi I; Katsura, Akihiro; Miyazono, Kohei

    2015-09-01

    The precise control of microRNA (miRNA) biosynthesis is crucial for gene regulation. Lin28A and Lin28B are selective inhibitors of biogenesis of let-7 miRNAs involved in development and tumorigenesis. Lin28A selectively inhibits let-7 biogenesis through cytoplasmic uridylation of precursor let-7 by TUT4 terminal uridyl transferase and subsequent degradation by Dis3l2 exonuclease. However, a role of this uridylation pathway remains unclear in let-7 blockade by Lin28B, a paralog of Lin28A, while Lin28B is reported to engage a distinct mechanism in the nucleus to suppress let-7. Here we revisit a functional link between Lin28B and the uridylation pathway with a focus on let-7 metabolism in cancer cells. Both Lin28A and Lin28B interacted with Dis3l2 in the cytoplasm, and silencing of Dis3l2 upregulated uridylated pre-let-7 in both Lin28A- and Lin28B-expressing cancer cell lines. In addition, we found that amounts of let-7 precursors influenced intracellular localization of Lin28B. Furthermore, we found that MCPIP1 (Zc3h12a) ribonuclease was also involved in degradation of both non-uridylated and uridylated pre-let-7. Cancer transcriptome analysis showed association of expression levels of Lin28B and uridylation pathway components, TUT4 and Dis3l2, in various human cancer cells and hepatocellular carcinoma. Collectively, these results suggest that cytoplasmic uridylation pathway actively participates in blockade of let-7 biogenesis by Lin28B. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  3. A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B

    PubMed Central

    Suzuki, Hiroshi I; Katsura, Akihiro; Miyazono, Kohei

    2015-01-01

    The precise control of microRNA (miRNA) biosynthesis is crucial for gene regulation. Lin28A and Lin28B are selective inhibitors of biogenesis of let-7 miRNAs involved in development and tumorigenesis. Lin28A selectively inhibits let-7 biogenesis through cytoplasmic uridylation of precursor let-7 by TUT4 terminal uridyl transferase and subsequent degradation by Dis3l2 exonuclease. However, a role of this uridylation pathway remains unclear in let-7 blockade by Lin28B, a paralog of Lin28A, while Lin28B is reported to engage a distinct mechanism in the nucleus to suppress let-7. Here we revisit a functional link between Lin28B and the uridylation pathway with a focus on let-7 metabolism in cancer cells. Both Lin28A and Lin28B interacted with Dis3l2 in the cytoplasm, and silencing of Dis3l2 upregulated uridylated pre-let-7 in both Lin28A- and Lin28B-expressing cancer cell lines. In addition, we found that amounts of let-7 precursors influenced intracellular localization of Lin28B. Furthermore, we found that MCPIP1 (Zc3h12a) ribonuclease was also involved in degradation of both non-uridylated and uridylated pre-let-7. Cancer transcriptome analysis showed association of expression levels of Lin28B and uridylation pathway components, TUT4 and Dis3l2, in various human cancer cells and hepatocellular carcinoma. Collectively, these results suggest that cytoplasmic uridylation pathway actively participates in blockade of let-7 biogenesis by Lin28B. PMID:26080928

  4. Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders.

    PubMed

    Mizuno, Makoto; Matsumoto, Ayumi; Hamada, Nanako; Ito, Hidenori; Miyauchi, Akihiko; Jimbo, Eriko F; Momoi, Mariko Y; Tabata, Hidenori; Yamagata, Takanori; Nagata, Koh-Ichi

    2015-01-01

    Using comparative genomic hybridization analysis for an autism spectrum disorder (ASD) patient, a 73-Kb duplication at 19q13.33 (nt. 49 562 755-49 635 956) including LIN7B and 5 other genes was detected. We then identified a novel frameshift mutation in LIN7B in another ASD patient. Since LIN7B encodes a scaffold protein essential for neuronal function, we analyzed the role of Lin-7B in the development of cerebral cortex. Acute knockdown of Lin-7B with in utero electroporation caused a delay in neuronal migration during corticogenesis. When Lin-7B was knocked down in cortical neurons in one hemisphere, their axons failed to extend efficiently into the contralateral hemisphere after leaving the corpus callosum. Meanwhile, enhanced expression of Lin-7B had no effects on both cortical neuron migration and axon growth. Notably, silencing of Lin-7B did not affect the proliferation of neuronal progenitors and stem cells. Taken together, Lin-7B was found to play a pivotal role in corticogenesis through the regulation of excitatory neuron migration and interhemispheric axon growth, while further analyses are required to directly link functional defects of Lin-7B to ASD pathophysiology. Lin-7 plays a pivotal role as a scaffold protein in synaptic development and plasticity. Based on genetic analyses we identified mutations in LIN-7B gene in some ASD (autism-spectrum disorder) patients. Functional defects in Lin-7B caused abnormal neuronal migration and interhemispheric axon growth during mouse brain development. Thus, functional deficiency in Lin-7B could be implicated in clinical phenotypes in some ASD patients through bringing about abnormal cortical architecture.

  5. Implementing a computerized text-management system: an editor's view

    SciTech Connect

    Mason, J.D.

    1980-01-01

    The advent of sophisticated function-key-driven programs for handling text on a video-display terminal enables the editorial staff of a publications department to take an active role on a computerized text-management team, along with compositors and other keyboard operators. Although there are still many things that editors cannot do on a computer terminal, the bulk of manipulating straight text can be speeded, and the problems of rekeyboarding and interpretation of editorial markings can be largely bypassed. The computer also gives editors new tools that open the way for greater control over both the editorial process and the quality of technical publishing. 5 figures.

  6. Featuring the special issue editor: associate professor Alexandros G. Georgakilas.

    PubMed

    Georgakilas, Alexandros G

    2012-12-31

    In this 'Featuring the editor' article, we introduce Assoc. Professor Alexandros G. Georgakilas as the guest editor for this Special Issue of Cancer Letters. His main research, educational and editorial achievements in his academic career are presented with emphasis on the various milestones of his involvement in science for more than twenty years. His primary interests in research focus on various radiation and cancer biology aspects especially the involvement of clustered DNA lesions in carcinogenesis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. EDITORIAL: New Editor-in-Chief for Nanotechnology New Editor-in-Chief for Nanotechnology

    NASA Astrophysics Data System (ADS)

    Couzin, Nina

    2009-01-01

    Nanotechnology is proud to announce the appointment of Professor Mark Reed, Yale University, as the new Editor-in-Chief from January 2009. Mark Reed holds the Harold Hodgkinson Chair of Engineering and Applied Science at Yale University. He has made significant contributions in the areas of quantum dots, electronic transport in nanoscale and mesoscopic systems, artificially structured materials and devices, and molecular electronics. Professor Reed has been associated with the journal as an Editorial Board member for a number of years and we are delighted that he has agreed to take on the scientific leadership of the journal in its 20th year. We also take the opportunity to thank Professor Mark Welland, Cambridge University, for his work as Editor-in-Chief since 2001, and for presiding over the re-launch and remarkable growth of the journal since then. Nanotechnology is unique in that it was the first peer-reviewed journal in the area of nanoscience, the first issue appearing in 1990. Since then it has established a distinguished publication record and has become a leading journal covering all aspects of nanoscale science and technology, as well as specializing in in-depth, comprehensive articles not seen in letter format journals. Published weekly and featuring subject sections, the journal is truly multidisciplinary in nature and is an excellent medium to quickly deliver your research results to readers worldwide. Nanotechnology is proud to be offering some of the fastest publication times around (less than three months on average from receipt to online publication). We offer free online access to all published papers for 30 days, ensuring that anyone with access to the internet will be able to read your paper. We were also the first journal to give our authors the opportunity to communicate their research to a wider audience through nanotechweb.org and other IOP websites. See the journal's homepage at www.iop.org/Journals/nano for more details. We are looking

  8. Human and murine amniotic fluid c-Kit+Lin- cells display hematopoietic activity.

    PubMed

    Ditadi, Andrea; de Coppi, Paolo; Picone, Olivier; Gautreau, Laetitia; Smati, Rim; Six, Emmanuelle; Bonhomme, Delphine; Ezine, Sophie; Frydman, René; Cavazzana-Calvo, Marina; André-Schmutz, Isabelle

    2009-04-23

    We have isolated c-Kit(+)Lin(-) cells from both human and murine amniotic fluid (AF) and investigated their hematopoietic potential. In vitro, the c-Kit(+)Lin(-) population in both species displayed a multilineage hematopoietic potential, as demonstrated by the generation of erythroid, myeloid, and lymphoid cells. In vivo, cells belonging to all 3 hematopoietic lineages were found after primary and secondary transplantation of murine c-Kit(+)Lin(-) cells into immunocompromised hosts, thus demonstrating the ability of these cells to self-renew. Gene expression analysis of c-Kit(+) cells isolated from murine AF confirmed these results. The presence of cells with similar characteristics in the surrounding amnion indicates the possible origin of AF c-Kit(+)Lin(-) cells. This is the first report showing that cells isolated from the AF do have hematopoietic potential; our results support the idea that AF may be a new source of stem cells for therapeutic applications.

  9. Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors' Network.

    PubMed

    Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

    The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability -, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors' Network of the European Society of Cardiology. Copyright © 2017. Publicado por Masson Doyma México S.A.

  10. Announcement: New Editor-In-Chief, Robert C. Kennicutt, Jr.

    NASA Astrophysics Data System (ADS)

    Abt, Helmut A.

    1999-06-01

    Effective 1999 July 1, all new manuscripts for Part 1 of The Astrophysical Journal and The Astrophysical Journal Supplement Series should be sent to Dr. Robert C. Kennicutt, Jr., Editor-in-Chief The Astrophysical Journal Steward Observatory University of Arizona Tucson, AZ 85721-0065 The other means of contact are telephone, (520) 621-5145 FAX, (520) 621-5153 and e-mail, apj@as.arizona.edu. For express packages please use the street address of 933 North Cherry Avenue. Dr. Kennicutt will be assisted by several of my loyal coworkers, who will move across the street. Manuscripts received before July 1 will be handled by the current editor until most of their problems have been resolved, at which point the remainder will be sent to Dr. Kennicutt's office. Manuscripts for the Letters should, as before, be sent directly to Dr. Alex Dalgarno at the Center for Astrophysics in Cambridge, MA. We are fortunate that a person with as much experience in research and proven good judgment as Dr. Kennicutt is willing to accept this difficult and time-consuming responsibility. He will be only the seventh Managing Editor or Editor-in-Chief that this Journal has had in its 104 years. Please give him the cooperation and help that you have given the current editor. It has been my privilege to work for 28 years with many of the best astrophysicists in the world and to publish their papers. This was done with the help of the AAS Publications Board and AAS officers, the efforts of Peter Boyce and Evan Owens who made the on-line edition of the Journal possible, three Associate Editors, a score of Scientific Editors, a hardworking staff of six in Tucson, up to 25 production controllers and manuscript editors at the University of Chicago Press, and the thousands of astronomers throughout the world who served as referees. The original masthead called this journal ``An International Review of Spectroscopy and Astronomical Physics.'' That subtitle is no longer appropriate because we do not

  11. Announcement: New Editor-In Robert C. Kennicutt

    NASA Astrophysics Data System (ADS)

    Abt, Helmut A.

    1999-06-01

    Effective 1999 July 1, all new manuscripts for Part 1 of The Astrophysical Journal and The Astrophysical Journal Supplement Series should be sent to Dr. Robert C. Kennicutt, Editor-in-Chief The Astrophysical Journal Steward Observatory University of Arizona Tucson, AZ 85721-0065 The other means of contact are telephone, (520) 621-5145 FAX, (520) 621-5153 and e-mail, apj@as.arizona.edu. For express packages please use the street address of 933 North Cherry Avenue. Dr. Kennicutt will be assisted by several of my loyal coworkers, who will move across the street. Manuscripts received before July 1 will be handled by the current editor until most of their problems have been resolved, at which point the remainder will be sent to Dr. Kennicutt's office. Manuscripts for the Letters should, as before, be sent directly to Dr. Alex Dalgarno at the Center for Astrophysics in Cambridge, MA. We are fortunate that a person with as much experience in research and proven good judgment as Dr. Kennicutt is willing to accept this difficult and time-consuming responsibility. He will be only the seventh Managing Editor or Editor-in-Chief that this Journal has had in its 104 years. Please give him the cooperation and help that you have given the current editor. It has been my privilege to work for 28 years with many of the best astrophysicists in the world and to publish their papers. This was done with the help of the AAS Publications Board and AAS officers, the efforts of Peter Boyce and Evan Owens who made the on-line edition of the Journal possible, three Associate Editors, a score of Scientific Editors, a hardworking staff of six in Tucson, up to 25 production controllers and manuscript editors at the University of Chicago Press, and the thousands of astronomers throughout the world who served as referees. The original masthead called this journal ``An International Review of Spectroscopy and Astronomical Physics.'' That subtitle is no longer appropriate because we do not publish

  12. Announcement: New Editor-in-Chief Robert C. Kennicutt

    NASA Astrophysics Data System (ADS)

    Abt, Helmut A.

    1999-05-01

    Effective 1999 July 1, all new manuscripts for Part 1 of The Astrophysical Journal and The Astrophysical Journal Supplement Series should be sent to Dr. Robert C. Kennicutt, Editor-in-Chief The Astrophysical Journal Steward Observatory University of Arizona Tucson, AZ 85721-0065 The other means of contact are telephone, (520) 621-5145 FAX, (520) 621-5153 and e-mail, apj@as.arizona.edu. For express packages please use the street address of 933 North Cherry Avenue. Dr. Kennicutt will be assisted by several of my loyal coworkers, who will move across the street. Manuscripts received before July 1 will be handled by the current editor until most of their problems have been resolved, at which point the remainder will be sent to Dr. Kennicutt's office. Manuscripts for the Letters should, as before, be sent directly to Dr. Alex Dalgarno at the Center for Astrophysics in Cambridge, MA. We are fortunate that a person with as much experience in research and proven good judgment as Dr. Kennicutt is willing to accept this difficult and time-consuming responsibility. He will be only the seventh Managing Editor or Editor-in-Chief that this Journal has had in its 104 years. Please give him the cooperation and help that you have given the current editor. It has been my privilege to work for 28 years with many of the best astrophysicists in the world and to publish their papers. This was done with the help of the AAS Publications Board and AAS officers, the efforts of Peter Boyce and Evan Owens who made the on-line edition of the Journal possible, three Associate Editors, a score of Scientific Editors, a hardworking staff of six in Tucson, up to 25 production controllers and manuscript editors at the University of Chicago Press, and the thousands of astronomers throughout the world who served as referees. The original masthead called this journal ``An International Review of Spectroscopy and Astronomical Physics.'' That subtitle is no longer appropriate because we do not publish

  13. LIN28 is involved in glioma carcinogenesis and predicts outcomes of glioblastoma multiforme patients.

    PubMed

    Qin, Rong; Zhou, Jingxu; Chen, Chao; Xu, Tao; Yan, Yong; Ma, Yushui; Zheng, Zongli; Shen, Yiping; Lu, Yicheng; Fu, Da; Chen, Juxiang

    2014-01-01

    LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 family microRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate and multivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients.

  14. LIN28 Is Involved in Glioma Carcinogenesis and Predicts Outcomes of Glioblastoma Multiforme Patients

    PubMed Central

    Xu, Tao; Yan, Yong; Ma, Yushui; Zheng, Zongli; Shen, Yiping; Lu, Yicheng; Fu, Da; Chen, Juxiang

    2014-01-01

    LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 family microRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate and multivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients. PMID:24475120

  15. LinA2, a HCH-converting bacterial enzyme that dehydrohalogenates HBCDs.

    PubMed

    Heeb, Norbert V; Wyss, Simon A; Geueke, Birgit; Fleischmann, Thomas; Kohler, Hans-Peter E; Lienemann, Peter

    2014-07-01

    Hexabromocyclododecanes (HBCDs) and hexachlorocyclohexanes (HCHs) are lipophilic, polyhalogenated hydrocarbons with comparable stereochemistry. Bacterial evolution in HCH-contaminated soils resulted in the development of several Spingomonadaceae which express a series of HCH-converting enzymes. We showed that LinB, a haloalkane dehalogenase from Sphingobium indicum B90A, also transforms various HBCDs besides HCHs. Here we present evidence that LinA2, another dehalogenase from S. indicum also converts certain HBCDs to pentabromocyclododecenes (PBCDEs). Racemic mixtures of α-, β-, γ-HBCDs, a mixture of them, and δ-HBCD, a meso form, were exposed to LinA2. Substantial conversion of (-)β-HBCD was observed, but all other stereoisomers were not transformed significantly. The enantiomeric excess (EE) of β-HBCDs increased up to 60% in 32 h, whereas EE values of α- and γ-HBCDs were not affected. Substrate conversion and product formation were described with second-order kinetic models. One major (P1β) and possibly two minor (P2β, P3β) metabolites were detected. Respective mass spectra showed the characteristic isotope pattern of PBCDEs, the HBr elimination products of HBCDs. Michaelis-Menten parameters KM=0.47 ± 0.07 μM and vmax=0.17 ± 0.01 μmoll(-1)h(-1) were deduced from exposure data with varying enzyme/substrate ratios. LinA2 is more substrate specific than LinB, the latter converted all tested HBCDs, LinA2 only one. The widespread HCH pollution favored the selection and evolution of bacteria converting these compounds. We found that LinA2 and LinB, two of these HCH-converting enzymes expressed in S. indicum B90A, also dehalogenate HBCDs to lower brominated compounds, indicating that structural similarities of both classes of compounds are recognized at the level of substrate-protein interactions.

  16. Multisite Phosphorylation of NuMA-Related LIN-5 Controls Mitotic Spindle Positioning in C. elegans

    PubMed Central

    Portegijs, Vincent; van Mourik, Tim; Akhmanova, Anna; Heck, Albert J. R.; van den Heuvel, Sander

    2016-01-01

    During cell division, the mitotic spindle segregates replicated chromosomes to opposite poles of the cell, while the position of the spindle determines the plane of cleavage. Spindle positioning and chromosome segregation depend on pulling forces on microtubules extending from the centrosomes to the cell cortex. Critical in pulling force generation is the cortical anchoring of cytoplasmic dynein by a conserved ternary complex of Gα, GPR-1/2, and LIN-5 proteins in C. elegans (Gα–LGN–NuMA in mammals). Previously, we showed that the polarity kinase PKC-3 phosphorylates LIN-5 to control spindle positioning in early C. elegans embryos. Here, we investigate whether additional LIN-5 phosphorylations regulate cortical pulling forces, making use of targeted alteration of in vivo phosphorylated residues by CRISPR/Cas9-mediated genetic engineering. Four distinct in vivo phosphorylated LIN-5 residues were found to have critical functions in spindle positioning. Two of these residues form part of a 30 amino acid binding site for GPR-1, which we identified by reverse two-hybrid screening. We provide evidence for a dual-kinase mechanism, involving GSK3 phosphorylation of S659 followed by phosphorylation of S662 by casein kinase 1. These LIN-5 phosphorylations promote LIN-5–GPR-1/2 interaction and contribute to cortical pulling forces. The other two critical residues, T168 and T181, form part of a cyclin-dependent kinase consensus site and are phosphorylated by CDK1-cyclin B in vitro. We applied a novel strategy to characterize early embryonic defects in lethal T168,T181 knockin substitution mutants, and provide evidence for sequential LIN-5 N-terminal phosphorylation and dephosphorylation in dynein recruitment. Our data support that phosphorylation of multiple LIN-5 domains by different kinases contributes to a mechanism for spatiotemporal control of spindle positioning and chromosome segregation. PMID:27711157

  17. Diabetes impairs mobilization of mouse bone marrow-derived Lin(-)/VEGF-R2(+) progenitor cells.

    PubMed

    Barthelmes, D; Irhimeh, M R; Gillies, M C; Karimipour, M; Zhou, M; Zhu, L; Shen, W Y

    2013-10-01

    Endothelial progenitor cells circulating in the peripheral blood (PB) contribute to vascular repair. This study aimed to evaluate the potential of a 'cocktail' consisting of erythropoietin, granulocyte colony-stimulating factor and tetrahydrobiopterin to mobilize hematopoietic lineage negative/vascular endothelial growth factor receptor 2 positive (Lin(-)/VEGF-R2(+)) cells from the bone marrow (BM) to PB in non-diabetic and diabetic mice. Diabetes was induced in mice by intraperitoneal injection of streptozotocin. Diabetic mice were studied after 16weeks of hyperglycemia. Half the mice in each group (non-diabetic and diabetic) received daily intraperitoneal injections of the cocktail for 6 consecutive days while the other half received vehicle buffer. Mobilization of Lin(-)/VEGF-R2(+) cells, which were expanded in MCP301 medium, was evaluated after isolating them from BM and PB and their phenotypic and morphological properties were studied. We found that 16weeks of diabetes affected neither the total number of BM mononucleated cells nor the number of Lin(-)/VEGF-R2(+) cells in BM compared with non-diabetic controls. In non-diabetic mice, cocktail treatment resulted in a significant decrease in BM Lin(-)/VEGF-R2(+) cells, paralleled by a significant increase of these cells in PB. Such changes in the number of Lin(-)/VEGF-R2(+) cells in BM and PB after the cocktail treatment were less marked in diabetic mice. In vitro studies of BM Lin(-)/VEGF-R2(+) cells from diabetic and non-diabetic mice did not reveal any differences in either phenotypes or colony forming potential. These findings indicate that diabetes impairs the mobilization of Lin(-)/VEGF-R2(+) cells from BM to PB. Impaired mobilization of BM Lin(-)/VEGF-R2(+) cells soon after the onset of diabetes may contribute to complications such as diabetic retinopathy.

  18. Another Security Improvement over the Lin et al.'s E-voting Scheme

    NASA Astrophysics Data System (ADS)

    Asaar, Maryam Rajabzadeh; Mohajeri, Javad; Salmasizadeh, Mahmoud

    In 2003, Lin et al. have proposed an electronic voting scheme which can be utilized in large-scale elections, and claimed it detects double voting. But in this paper, by presenting an attack, we show that voters can successfully vote more than once without being detected. Hence, we propose a new modified scheme based on the Lin et al.'s scheme with the same efficiency to solve this weakness and analyze its security.

  19. RbAp46/48(LIN-53) Is Required for Holocentromere Assembly in Caenorhabditis elegans.

    PubMed

    Lee, Bernard Chi Hang; Lin, Zhongyang; Yuen, Karen Wing Yee

    2016-03-01

    Centromeres, the specialized chromosomal regions for recruiting kinetochores and directing chromosome segregation, are epigenetically marked by a centromeric histone H3 variant, CENP-A. To maintain centromere identity through cell cycles, CENP-A diluted during DNA replication is replenished. The licensing factor M18BP1(KNL-2) is known to recruit CENP-A to holocentromeres. Here, we show that RbAp46/48(LIN-53), a conserved histone chaperone, is required for CENP-A(HCP-3) localization in holocentric Caenorhabditis elegans. Indeed, RbAp46/48(LIN-53) and CENP-A(HCP-3) localizations are interdependent. RbAp46/48(LIN-53) localizes to the centromere during metaphase in a CENP-A(HCP-3)- and M18BP1(KNL-2)-dependent manner, suggesting CENP-A(HCP-3) loading may occur before anaphase. RbAp46/48(LIN-53) does not function at the centromere through histone acetylation, H3K27 trimethylation, or its known chromatin-modifying complexes. RbAp46/48(LIN-53) may function independently to escort CENP-A(HCP-3) for holocentromere assembly but is dispensable for other kinetochore protein recruitment. Nonetheless, depletion of RbAp46/48(LIN-53) leads to anaphase bridges and chromosome missegregation. This study unravels the holocentromere assembly hierarchy and its conservation with monocentromeres.

  20. LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR).

    PubMed

    Korshunov, Andrey; Ryzhova, Marina; Jones, David T W; Northcott, Paul A; van Sluis, Peter; Volckmann, Richard; Koster, Jan; Versteeg, Rogier; Cowdrey, Cynthia; Perry, Arie; Picard, Daniel; Rosenblum, Marc; Giangaspero, Felice; Aronica, Eleonora; Schüller, Ulrich; Hasselblatt, Martin; Collins, V Peter; von Deimling, Andreas; Lichter, Peter; Huang, Annie; Pfister, Stefan M; Kool, Marcel

    2012-12-01

    Embryonal tumor with multilayered rosettes (ETMR, previously known as ETANTR) is a highly aggressive embryonal CNS tumor, which almost exclusively affects infants and is associated with a dismal prognosis. Accurate diagnosis is of critical clinical importance because of its poor response to current treatment protocols and its distinct biology. Amplification of the miRNA cluster at 19q13.42 has been identified previously as a genetic hallmark for ETMR, but an immunohistochemistry-based assay for clinical routine diagnostics [such as INI-1 for atypical teratoid rhabdoid tumor (AT/RT)] is still lacking. In this study, we screened for an ETMR-specific marker using a gene-expression profiling dataset of more than 1,400 brain tumors and identified LIN28A as a highly specific marker for ETMR. The encoded protein binds small RNA and has been implicated in stem cell pluripotency, metabolism and tumorigenesis. Using an LIN28A specific antibody, we carried out immunohistochemical analysis of LIN28A in more than 800 childhood brain-tumor samples and confirmed its high specificity for ETMR. Strong LIN28A immunoexpression was found in all 37 ETMR samples tested, whereas focal reactivity was only present in a small (6/50) proportion of AT/RT samples. All other pediatric brain tumors were completely LIN28A-negative. In summary, we established LIN28A immunohistochemistry as a highly sensitive and specific, rapid, inexpensive diagnostic tool for routine pathological verification of ETMR.

  1. Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation.

    PubMed

    Tan, Shen Mynn; Altschuler, Gabriel; Zhao, Tian Yun; Ang, Haw Siang; Yang, Henry; Lim, Bing; Vardy, Leah; Hide, Winston; Thomson, Andrew M; Lareu, Ricky R

    2014-07-01

    LIN28 function is fundamental to the activity and behavior of human embryonic stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these cell types are the regulation of translational efficiency and let-7 miRNA maturation. However, LIN28-associated mRNA cargo shifting and resultant regulation of translational efficiency upon the initiation of differentiation remain unknown. An RNA-immunoprecipitation and microarray analysis protocol, eRIP, that has high specificity and sensitivity was developed to test endogenous LIN28-associated mRNA cargo shifting. A combined eRIP and polysome analysis of early stage differentiation of hESCs with two distinct differentiation cues revealed close similarities between the dynamics of LIN28 association and translational modulation of genes involved in the Wnt signaling, cell cycle, RNA metabolism and proteasomal pathways. Our data demonstrate that change in translational efficiency is a major contributor to early stages of differentiation of hESCs, in which LIN28 plays a central role. This implies that eRIP analysis of LIN28-associated RNA cargoes may be used for rapid functional quality control of pluripotent stem cells under manufacture for therapeutic applications. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression.

    PubMed

    Triboulet, Robinson; Pirouz, Mehdi; Gregory, Richard I

    2015-10-13

    Let-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain 12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28 proteins selectively block let-7 biogenesis in undifferentiated cells and in cancer. The current model for coordinate let-7 repression involves the LIN28 cold-shock domain (CSD) binding the terminal loop and the two CCHC-type zinc fingers recognizing a GGAG sequence motif in precursor let-7 (pre-let-7) RNAs. Here, we perform a systematic analysis of all let-7 miRNAs and find that a single let-7 family member, human let-7a-3 (and its murine ortholog let-7c-2), escapes LIN28-mediated regulation. Mechanistically, we find that the pre-let-7c-2 loop precludes LIN28A binding and regulation. These findings refine the current model of let-7 regulation by LIN28 proteins and have important implications for understanding the LIN28/let-7 axis in development and disease. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation

    PubMed Central

    Tan, Shen Mynn; Altschuler, Gabriel; Zhao, Tian Yun; Ang, Haw Siang; Yang, Henry; Lim, Bing; Vardy, Leah; Hide, Winston; Thomson, Andrew M.; Lareu, Ricky R.

    2014-01-01

    LIN28 function is fundamental to the activity and behavior of human embryonic stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these cell types are the regulation of translational efficiency and let-7 miRNA maturation. However, LIN28-associated mRNA cargo shifting and resultant regulation of translational efficiency upon the initiation of differentiation remain unknown. An RNA-immunoprecipitation and microarray analysis protocol, eRIP, that has high specificity and sensitivity was developed to test endogenous LIN28-associated mRNA cargo shifting. A combined eRIP and polysome analysis of early stage differentiation of hESCs with two distinct differentiation cues revealed close similarities between the dynamics of LIN28 association and translational modulation of genes involved in the Wnt signaling, cell cycle, RNA metabolism and proteasomal pathways. Our data demonstrate that change in translational efficiency is a major contributor to early stages of differentiation of hESCs, in which LIN28 plays a central role. This implies that eRIP analysis of LIN28-associated RNA cargoes may be used for rapid functional quality control of pluripotent stem cells under manufacture for therapeutic applications. PMID:24860167

  4. Novel LINS1 missense mutation in a family with non-syndromic intellectual disability.

    PubMed

    Sheth, Jayesh; Ranjan, Gyan; Shah, Krati; Bhavsar, Riddhi; Sheth, Frenny

    2017-04-01

    Newer sequencing technologies decipher molecular variations and increase the knowledge of pathogenesis of complex diseases like intellectual disability (ID), affecting 2-3% of the population. We report a novel family with a missense mutation in LINS1 as a cause for non-syndromic ID. Clinical exome sequencing for ID related genes carried out for a male with dysmorphism, mutism, and cognitive delay was uninformative. Subsequently, "pathogenic" and "likely pathogenic" variants associated with other inherited disorders were searched for as secondary findings. Further, PCR-RFLP carried out in other family members confirmed the result. A novel missense variant (c.937G>A) in exon 5 of LINS1 was detected in the proband. His affected elder brother was homozygous and the parents were heterozygous respectively, for the mutation. No mutation was observed in his unaffected sister. Mutations in LINS1 were suspected in this non-syndromic ID case with mutism. LINS1 alterations affect ELAV1 expression and result in reduction in the commissural axonal growth, thus affecting peripheral and central neuronal function. LINS1 acts in association with β-catenin to influence WNT1 signaling. It is hypothesized that mutations in LINS1 may alter HuR expression during neural differentiation, leading to ID in humans. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Structure and Mechanism of the Lincosamide Antibiotic adenylyltransferase LinB

    SciTech Connect

    Morar, M.; Buhllar, K; Hughes, D; Junop, M; Wright, G

    2009-01-01

    Lincosamides make up an important class of antibiotics used against a wide range of pathogens, including methicillin-resistant Staphylococcus aureus. Predictably, lincosamide-resistant microorganisms have emerged with antibiotic modification as one of their major resistance strategies. Inactivating enzymes LinB/A catalyze adenylylation of the drug; however, little is known about their mechanistic and structural properties. We determined two X-ray structures of LinB: ternary substrate and binary productbound complexes. Structural and kinetic characterization of LinB, mutagenesis, solvent isotope effect, and product inhibition studies are consistent with a mechanism involving direct in-line nucleotidyl transfer. The characterization of LinB enabled its classification as a member of a nucleotidyltransferase superfamily, along with nucleotide polymerases and aminoglycoside nucleotidyltransferases, and this relationship offers further support for the LinB mechanism. The LinB structure provides an evolutionary link to ancient nucleotide polymerases and suggests that, like protein kinases and acetyltransferases, these are proto-resistance elements from which drug resistance can evolve.

  6. Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7

    PubMed Central

    Dangi-Garimella, Surabhi; Yun, Jieun; Eves, Eva M; Newman, Martin; Erkeland, Stefan J; Hammond, Scott M; Minn, Andy J; Rosner, Marsha Rich

    2009-01-01

    Raf kinase inhibitory protein (RKIP) negatively regulates the MAP kinase (MAPK), G protein-coupled receptor kinase-2, and NF-κB signalling cascades. RKIP has been implicated as a metastasis suppressor for prostate cancer, but the mechanism is not known. Here, we show that RKIP inhibits invasion by metastatic breast cancer cells and represses breast tumour cell intravasation and bone metastasis in an orthotopic murine model. The mechanism involves inhibition of MAPK, leading to decreased transcription of LIN28 by Myc. Suppression of LIN28 enables enhanced let-7 processing in breast cancer cells. Elevated let-7 expression inhibits HMGA2, a chromatin remodelling protein that activates pro-invasive and pro-metastatic genes, including Snail. LIN28 depletion and let-7 expression suppress bone metastasis, and LIN28 restores bone metastasis in mice bearing RKIP-expressing breast tumour cells. These results indicate that RKIP suppresses invasion and metastasis in part through a signalling cascade involving MAPK, Myc, LIN28, let-7, and downstream let-7 targets. RKIP regulation of two pluripotent stem cell genes, Myc and LIN28, highlights the importance of RKIP as a key metastasis suppressor and potential therapeutic agent. PMID:19153603

  7. TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling.

    PubMed

    Yin, Jinlong; Kim, Tae-Hoon; Park, Nayun; Shin, Daye; Choi, Hae In; Cho, Sungchan; Park, Jong Bae; Kim, Jong Heon

    2016-11-29

    TRIM71 (tripartite motif-containing 71) belongs to the TRIM-NHL protein family, which plays a conserved role in regulating early development and differentiation. However, the molecular functions of TRIM71 have remained largely unknown. Here, we explored the role of TRIM71 together with modulation of Lin28B-let-7-HMGA2 (high-mobility group AT-hook 2) signaling in tumorigenesis. TRIM71 overexpression opposed Lin28B-induced transformation in primary cells and inhibited tumor formation in a mouse model. Specific knockdown of TRIM71 expression increased cancer cell proliferation and invasion. Conversely, overexpression of wild-type TRIM71 in non-small cell lung carcinoma (NSCLC) cells in which Lin28B-let-7-HMGA2 signaling was conserved decreased both cancer cell phenotypes. More importantly, overexpression of an ubiquitin transfer activity-deficient TRIM71 mutant in NSCLC cells had no effect on proliferation or invasion, regardless of the conservation status of Lin28B-let-7-HMGA2 signaling. The tumorigenic inhibitory action of TRIM71 was antagonized by overexpression of the TRIM71 downstream targets, Lin28B and HMGA2. Furthermore, a bioinformatics analysis revealed that TRIM71 expression was downregulated in various types of cancer tissue from patients. Taken together, these data indicate that TRIM71 acts through post-transcriptional repression of Lin28B and subsequent modulation of let-7-HMGA2 signaling during tumorigenesis to potentially function as a tumor suppressor.

  8. TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling

    PubMed Central

    Yin, Jinlong; Kim, Tae-Hoon; Park, Nayun; Shin, Daye; Choi, Hae In; Cho, Sungchan; Park, Jong Bae; Kim, Jong Heon

    2016-01-01

    TRIM71 (tripartite motif-containing 71) belongs to the TRIM-NHL protein family, which plays a conserved role in regulating early development and differentiation. However, the molecular functions of TRIM71 have remained largely unknown. Here, we explored the role of TRIM71 together with modulation of Lin28B-let-7-HMGA2 (high-mobility group AT-hook 2) signaling in tumorigenesis. TRIM71 overexpression opposed Lin28B-induced transformation in primary cells and inhibited tumor formation in a mouse model. Specific knockdown of TRIM71 expression increased cancer cell proliferation and invasion. Conversely, overexpression of wild-type TRIM71 in non-small cell lung carcinoma (NSCLC) cells in which Lin28B-let-7-HMGA2 signaling was conserved decreased both cancer cell phenotypes. More importantly, overexpression of an ubiquitin transfer activity-deficient TRIM71 mutant in NSCLC cells had no effect on proliferation or invasion, regardless of the conservation status of Lin28B-let-7-HMGA2 signaling. The tumorigenic inhibitory action of TRIM71 was antagonized by overexpression of the TRIM71 downstream targets, Lin28B and HMGA2. Furthermore, a bioinformatics analysis revealed that TRIM71 expression was downregulated in various types of cancer tissue from patients. Taken together, these data indicate that TRIM71 acts through post-transcriptional repression of Lin28B and subsequent modulation of let-7-HMGA2 signaling during tumorigenesis to potentially function as a tumor suppressor. PMID:27821801

  9. Lin28b stimulates the reprogramming of rat Müller glia to retinal progenitors.

    PubMed

    Zhao, Chen; Tao, Zui; Xue, Langyue; Zeng, Yuxiao; Wang, Yi; Xu, Haiwei; Yin, Zheng Qin

    2017-03-01

    In lower-order vertebrates, Müller glia exhibit characteristics of retinal progenitor cells, while in higher vertebrates, such as mammals, the regenerative capacity of Müller glia is limited. Recently, we reported that Lin28b promoted the trans-differentiation of Müller cells to rod photoreceptor and bipolar cells in the retina of retinitis pigmentosa rat model, whereas it is unclear whether Lin28b can stimulate the reprogramming of Müller glia in vitro for transplantation into a damaged retina. In the present study, Long-Evens rat Müller glia were infected with Adeno-Lin28b or Adeno-GFP. Over-expression of Lin28b in isolated rat Müller glia resulted in the suppression of GFAP expression, enhancement of cell proliferation and a significant increase of the expression of retinal progenitor markers 5 days after infection. Moreover, Lin28b caused a significant reduction of the Let-7 family of microRNAs. Following sub-retinal space transplantation, Müller glia-derived retinal progenitors improved b-wave amplification of 30d Royal College of Surgeons retinitis pigmentosa model (RCS-P+) rats, as detected by electroretinography (ERG) recordings. Taken together, these data suggest that the up-regulation of Lin28b expression facilitated the reprogramming of Müller cells toward characteristics of retinal progenitors.

  10. Assessment of X Chromosome Dosage Compensation in Caenorhabditis elegans by Phenotypic Analysis of lin-14

    PubMed Central

    DeLong, Leslie; Casson, Lawrence P.; Meyer, Barbara J.

    1987-01-01

    Caenorhabditis elegans compensates for the difference in X chromosome gene dose between males (XO) and hermaphrodites (XX) through a mechanism that equalizes the levels of X-specific mRNA transcripts between the two sexes. We have devised a sensitive and quantitative genetic assay to measure perturbations in X chromosome gene expression caused by mutations that affect this process of dosage compensation. The assay is based on quantitating the precocious alae phenotype caused by a mutation that reduces but does not eliminate the function of the X-linked gene lin-14. We demonstrate that in diploid animals the lin-14 gene is dosage compensated between XO and XX animals. In XXX diploid animals, however, lin-14 expression is not compensated, implying that the normal dosage compensation mechanism in C. elegans lacks the capacity to compensate completely for the additional X chromosome in triplo-X animals. Using the lin-14 assay we compare the effects of mutations in the genes dpy-21, dpy-26, dpy-27, dpy-28, and dpy-22 on X-linked gene expression. Additionally, in the case of dpy-21 we correlate the change in phenotypic expression of lin-14 with a corresponding change in the lin-14 mRNA transcript level. PMID:3428573

  11. Quantitative evaluation of the transplanted lin(-) hematopoietic cell migration kinetics.

    PubMed

    Kašėta, Vytautas; Vaitkuvienė, Aida; Liubavičiūtė, Aušra; Maciulevičienė, Rūta; Stirkė, Arūnas; Biziulevičienė, Genė

    2016-02-01

    Stem cells take part in organogenesis, cell maturation and injury repair. The migration is necessary for each of these functions to occur. The aim of this study was to investigate the kinetics of transplanted hematopoietic lin(-) cell population (which consists mainly of the stem and progenitor cells) in BALB/c mouse contact hypersensitivity model and quantify the migration to the site of inflammation in the affected foot and other healthy organs. Quantitative analysis was carried out with the real-time polymerase chain reaction method. Spleen, kidney, bone marrow, lung, liver, damaged and healthy foot tissue samples at different time points were collected for analysis. The quantitative data normalization was performed according to the comparative quantification method. The analysis of foot samples shows the significant migration of transplanted cells to the recipient mice affected foot. The quantity was more than 1000 times higher, as compared with that of the untreated foot. Due to the inflammation, the number of donor origin cells migrating to the lungs, liver, spleen and bone marrow was found to be decreased. Our data shows that transplanted cells selectively migrated into the inflammation areas of the foot edema. Also, the inflammation caused a secondary migration in ectopic spleen of hematopoietic stem cell niches and re-homing from the spleen to the bone marrow took place.

  12. CancerLinQ and the future of cancer care.

    PubMed

    Sledge, George W; Miller, Robert S; Hauser, Robert

    2013-01-01

    Patients, health care providers, and payers all have a similar interest in a health care system that is both efficient and intelligent. The attributes of such a system are widely recognized: we want a system that provides widespread access to consistently high-quality, science-based medical care; we want that system to be efficient, avoiding unnecessary waste, while delivering the right treatments to the right patients in a timely fashion; we want a system that allows us to both learn from our experience and generate new knowledge that will inform future treatment options; and we want a system that is compassionate and caring. What we want from a health care system often runs up against real-life obstacles and challenges: a fragmented delivery system, varying levels (or lack of) insurance, a growing burden of regulation and paperwork, and an increasingly complex understanding of tumor biology and the therapeutic approaches derived from this biology. New challenges are on the horizon-emerging genomic and imaging technology, with their enormous cognitive and data burdens, and a looming demographic challenge, where inadequate personnel resources face an aging population and an explosion of new treatments. Not all problems have technologic solutions, but many of the issues described above have potential solutions related to information technology. ASCO's CancerLinQ, described in this article, is an evolving attempt by the Society to improve the quality and efficiency of cancer care, while supporting education and research in the cancer field.

  13. Lin41/Trim71 is essential for mouse development and specifically expressed in postnatal ependymal cells of the brain.

    PubMed

    Cuevas, Elisa; Rybak-Wolf, Agnieszka; Rohde, Anna M; Nguyen, Duong T T; Wulczyn, F Gregory

    2015-01-01

    Lin41/Trim71 is a heterochronic gene encoding a member of the Trim-NHL protein family, and is the original, genetically defined target of the microRNA let-7 in C. elegans. Both the LIN41 protein and multiple regulatory microRNA binding sites in the 3' UTR of the mRNA are highly conserved from nematodes to humans. Functional studies have described essential roles for mouse LIN41 in embryonic stem cells, cellular reprogramming and the timing of embryonic neurogenesis. We have used a new gene trap mouse line deficient in Lin41 to characterize Lin41 expression during embryonic development and in the postnatal central nervous system (CNS). In the embryo, Lin41 is required for embryonic viability and neural tube closure. Nevertheless, neurosphere assays suggest that Lin41 is not required for adult neurogenesis. Instead, we show that Lin41 promoter activity and protein expression in the postnatal CNS is restricted to ependymal cells lining the walls of the four ventricles. We use ependymal cell culture to confirm reestablishment of Lin41 expression during differentiation of ependymal progenitors to post-mitotic cells possessing motile cilia. Our results reveal that terminally differentiated ependymal cells express Lin41, a gene to date associated with self-renewing stem cells.

  14. Developing and Presenting Auditory Demonstrations: Two Sound Editor Programs

    ERIC Educational Resources Information Center

    Firment, Michael J.

    2006-01-01

    Experiencing examples of auditory phenomena can clarify textbook and lecture explanations. The addition of visual displays to auditory demonstrations can make them more understandable. Two sound editor programs, Audacity[R] and Adobe Audition Pro 2.0[R], provide excellent capabilities for the display and authoring of auditory demonstrations.…

  15. IN DEFENSE OF ECORISK ASSESSMENT (LETTER TO EDITOR)

    EPA Science Inventory

    Dear Editor: We are writing to convey a more accurate portrayal of the status of ecological ("environmental" in Europe) risk assessment that was presented in the recent article by M. Power and L.S. McCarty (Fallacies in Ecological Risk Assessment Practices," August 1997, pp 370A-...

  16. Most Business Editors Find Journalism Graduates Still Unprepared

    ERIC Educational Resources Information Center

    Pardue, Mary Jane

    2014-01-01

    In 2002, a study was published in "Newspaper Research Journal" that explored the preparedness of graduating journalism students to cover business news. In 2012, a follow-up survey of business editors at the nation's daily newspapers was done to see whether progress had been made in the training of journalism students for the…

  17. Ethical dilemmas in scientific publication: pitfalls and solutions for editors.

    PubMed

    Gollogly, Laragh; Momen, Hooman

    2006-08-01

    Editors of scientific journals need to be conversant with the mechanisms by which scientific misconduct is amplified by publication practices. This paper provides definitions, ways to document the extent of the problem, and examples of editorial attempts to counter fraud. Fabrication, falsification, duplication, ghost authorship, gift authorship, lack of ethics approval, non-disclosure, 'salami' publication, conflicts of interest, auto-citation, duplicate submission, duplicate publications, and plagiarism are common problems. Editorial misconduct includes failure to observe due process, undue delay in reaching decisions and communicating these to authors, inappropriate review procedures, and confounding a journal's content with its advertising or promotional potential. Editors also can be admonished by their peers for failure to investigate suspected misconduct, failure to retract when indicated, and failure to abide voluntarily by the six main sources of relevant international guidelines on research, its reporting and editorial practice. Editors are in a good position to promulgate reasonable standards of practice, and can start by using consensus guidelines on publication ethics to state explicitly how their journals function. Reviewers, editors, authors and readers all then have a better chance to understand, and abide by, the rules of publishing.

  18. What Authors Want From Journal Reviewers and Editors

    ERIC Educational Resources Information Center

    Nickerson, Raymond S.

    2005-01-01

    Peer review is the primary means of ensuring the maintenance of standards that are deemed appropriate for scientific publications. There are many similarities, but also some differences, in the way the review process is conducted by different editors, and there are differences among reviewers in how they deal with the same manuscript--the…

  19. Females' participation in psychopharmacology research as authors, editors, and subjects.

    PubMed

    Poling, Alan; Durgin, Amy; Bradley, Kelly P; Porter, Lindsay K; Van Wagner, Karen; Weeden, Marc; Panos, John J

    2009-04-01

    This study determined the involvement of women as first authors and other authors for every article published in Experimental and Clinical Psychopharmacology, Pharmacology Biochemistry and Behavior, and Psychopharmacology in 1991, 1996, 2001, and 2006. Their involvement as editors also was determined. Women's participation as authors, but not as editors, slightly increased over time. In 2006, 43% of first authors, 38% of other authors, and 24% of editors were women. The gender of subjects was examined for the same years and journals, but could not be determined for 6% and 9% of articles employing nonhuman and human subjects, respectively. In 2006, when subjects' gender could be determined, 77% of articles involving nonhuman subjects used only males, 9% only females, and 14% both males and females. In articles using human subjects in that same year, 17% involved only males, 6% only females, and 77% both males and females. Women researchers clearly make substantial contributions to the psychopharmacology literature, but are nonetheless underrepresented as editors. Findings regarding subjects indicate that there is growing recognition of the importance of gender as a determinant of drug effects, although the vast majority of nonhuman studies continue to involve only male subjects.

  20. Particle size fraction -Response: Letter to the Editors

    EPA Science Inventory

    To the Editors: We, the undersigned, would like to comment on the article by Cho et al. (Cho et al. 2009), which was published in the November 2009 issue (volume 11, number 11, page 1682-1689) of Environmental Health Perspectives. We read the paper with great interest as the dis...

  1. August 2017 Letters to the Editor-in-Chief.

    PubMed

    2017-08-01

    Letter to the Editor-in-Chief of JOSPT as follows: "Manual Therapy: More Than Elaborate Swordplay" with Authors' Response "Comparing Dry Needling to Corticosteroid Injection for Greater Trochanteric Pain Syndrome" with Authors' Response J Orthop Sports Phys Ther 2017;47(8):580-585. doi:10.2519/jospt.2017.0204.

  2. September 2017 Letter to the Editor-in-Chief.

    PubMed

    2017-09-01

    Letter to the Editor-in-Chief of JOSPT as follows: "Clinically Meaningful Outcome Measures in Patients With Shoulder Problems" with Authors' Response J Orthop Sports Phys Ther 2017;47(9):693-695. doi:10.2519/jospt.2017.0205.

  3. LACE: A Web-Based, Structured Editor for PDS Metadata

    NASA Astrophysics Data System (ADS)

    Rose, M.; Keller, R.; Sarram, P.

    2015-06-01

    PDS has moved to XML-based metadata, but many scientists are not familiar with XML and find its structure complicated. For these reasons, we have created LACE, an editor for PDS metadata that hides the complexity of XML from the user.

  4. Particle size fraction -Response: Letter to the Editors

    EPA Science Inventory

    To the Editors: We, the undersigned, would like to comment on the article by Cho et al. (Cho et al. 2009), which was published in the November 2009 issue (volume 11, number 11, page 1682-1689) of Environmental Health Perspectives. We read the paper with great interest as the dis...

  5. Most Business Editors Find Journalism Graduates Still Unprepared

    ERIC Educational Resources Information Center

    Pardue, Mary Jane

    2014-01-01

    In 2002, a study was published in "Newspaper Research Journal" that explored the preparedness of graduating journalism students to cover business news. In 2012, a follow-up survey of business editors at the nation's daily newspapers was done to see whether progress had been made in the training of journalism students for the…

  6. IN DEFENSE OF ECORISK ASSESSMENT (LETTER TO EDITOR)

    EPA Science Inventory

    Dear Editor: We are writing to convey a more accurate portrayal of the status of ecological ("environmental" in Europe) risk assessment that was presented in the recent article by M. Power and L.S. McCarty (Fallacies in Ecological Risk Assessment Practices," August 1997, pp 370A-...

  7. Righting the Wrongs of Writing: Copy Editors Speak Out

    ERIC Educational Resources Information Center

    Alexander, Jaclyn J.; Wall, Judy

    1975-01-01

    The major part of APGA Press production editors' jobs is copy editing manuscripts before they are set in type. Two APGA Press Staff members use specific examples to illustrate the grammatical and stylistic errors that cause problems for them and, if not corrected, for readers. (Author)

  8. Manuals for Editors and Authors: A Decision Model.

    ERIC Educational Resources Information Center

    Kirschner, Paul A.

    A series of eight manuals dealing with the triad text characteristics--learning processes--learning outcomes are being prepared for use by authors and editors as an aid in the design and writing of educational texts. These manuals are based upon a model for the functioning of text characteristics which in turn is part of a decision model for the…

  9. Publishing in Educational Psychology Journals: Comments from Editors

    ERIC Educational Resources Information Center

    Nihalani, Priya K.; Mayrath, Michael C.

    2008-01-01

    The following paper emphasizes the importance of publishing and learning how to publish in educational psychology journals. We have compiled a set of recommendations based on advice from editors in the field and several other sources on how to publish. Additionally, this paper provides a step-by-step guide that graduate students and junior faculty…

  10. An Editor's View of the State of Applied Developmental Psychology.

    ERIC Educational Resources Information Center

    Cocking, Rodney R.

    Addressed are issues and problems of definition that arose in establishing a new scientific journal. Specifically, the problems considered are those confronting the "Journal of Applied Developmental Psychology" (JADP) in its first 5 years of existence. The first matter of definition discussed is the editor's role. Ways in which editorial…

  11. Publishing in Educational Psychology Journals: Comments from Editors

    ERIC Educational Resources Information Center

    Nihalani, Priya K.; Mayrath, Michael C.

    2008-01-01

    The following paper emphasizes the importance of publishing and learning how to publish in educational psychology journals. We have compiled a set of recommendations based on advice from editors in the field and several other sources on how to publish. Additionally, this paper provides a step-by-step guide that graduate students and junior faculty…

  12. How about the Real World? Students Learn from Experienced Editors.

    ERIC Educational Resources Information Center

    Black, Sharon; Wilcox, Brad

    1998-01-01

    Surveys professional editors (who work with publishing companies and magazines with national and international circulations) concerning advice to students on how writers write. Finds four main themes: (1) plan and organize carefully; (2) revise your work thoughtfully; (3) use words purposefully; and (4) correct errors thoroughly. (RS)

  13. The Editor and the Fund Raiser: Partners or Adversaries?

    ERIC Educational Resources Information Center

    Collins, Walt; Hincker, Lawrence; Yoe, Mary Ruth; Loyless, Darrell

    1999-01-01

    In a panel format, experienced college publications editors and development professionals discussed their responses to three scenarios describing clashes between alumni magazine staff and development officers: writing donor profiles; reporting negative campus news; and publishing campaign materials in the alumni magazine. Excerpts of the…

  14. A potential regulatory loop between Lin28B:miR‑212 in androgen-independent prostate cancer.

    PubMed

    Borrego-Diaz, Emma; Powers, Benjamin C; Azizov, Vugar; Lovell, Scott; Reyes, Ruben; Chapman, Bradley; Tawfik, Ossama; McGregor, Douglas; Diaz, Francisco J; Wang, Xinkun; Veldhuizen, Peter Van

    2014-12-01

    Lin28 is a family of RNA binding proteins and microRNA regulators. Two members of this family have been identified: Lin28A and Lin28B, which are encoded by genes localized in different chromosomes but share a high degree of sequence identity. The role of Lin28B in androgen-independent prostate cancer (AIPC) is not well understood. Lin28B is expressed in all grades of prostatic carcinomas and prostate cancer cell lines, but not in normal prostate tissue. In this study we found that Lin28B co-localized in the nucleus and cytoplasm of the DU145 AIPC. The expression of Lin28B protein positively correlated with the expression of the c-Myc protein in the prostate cancer cell lines and silencing of Lin28B also correlated with a lower expression of the c-Myc protein, but not with the downregulation of c-Myc messenger RNA (mRNA) in the DU145 AIPC cells. We hypothesized that Lin28B regul-ates the expression of c-Myc protein by altering intermediate c-Myc suppressors. Therefore, a microRNA profile of DU145 cells was performed after Lin28B siRNA silencing. Nineteen microRNAs were upregulated and eleven microRNAs were downregulated. The most upregulated microRNAs were miR-212 and miR-2278. Prior reports have found that miR-212 is suppressed in prostate cancer. We then ran TargetScan software to find potential target mRNAs of miR-212 and miR-2278, and it predicted Lin28B mRNA as a potential target of miR-212, but not miR-2278. TargetScan also predicted that c-Myc mRNA is not a potential target of miR-212 or miR-2278. These observations suggest that Lin28B:miR-212 may work as a regulatory loop in androgen-independent prostate cancer. Furthermore, we report a predictive 2-fold symmetric model generated by the superposition of the Lin28A structure onto the I-TASSER model of Lin28B. This structural model of Lin28B suggests that it shows unique microRNA binding characteristics. Thus, if Lin28B were to bind miRNAs in a manner similar to Lin28A, conformational changes would be

  15. A potential regulatory loop between Lin28B:miR-212 in androgen-independent prostate cancer

    PubMed Central

    BORREGO-DIAZ, EMMA; POWERS, BENJAMIN C.; AZIZOV, VUGAR; LOVELL, SCOTT; REYES, RUBEN; CHAPMAN, BRADLEY; TAWFIK, OSSAMA; McGREGOR, DOUGLAS; DIAZ, FRANCISCO J.; WANG, XINKUN; VAN VELDHUIZEN, PETER

    2014-01-01

    Lin28 is a family of RNA binding proteins and microRNA regulators. Two members of this family have been identified: Lin28A and Lin28B, which are encoded by genes localized in different chromosomes but share a high degree of sequence identity. The role of Lin28B in androgen-independent prostate cancer (AIPC) is not well understood. Lin28B is expressed in all grades of prostatic carcinomas and prostate cancer cell lines, but not in normal prostate tissue. In this study we found that Lin28B co-localized in the nucleus and cytoplasm of the DU145 AIPC. The expression of Lin28B protein positively correlated with the expression of the c-Myc protein in the prostate cancer cell lines and silencing of Lin28B also correlated with a lower expression of the c-Myc protein, but not with the downregulation of c-Myc messenger RNA (mRNA) in the DU145 AIPC cells. We hypothesized that Lin28B regulates the expression of c-Myc protein by altering intermediate c-Myc suppressors. Therefore, a microRNA profile of DU145 cells was performed after Lin28B siRNA silencing. Nineteen microRNAs were upregulated and eleven microRNAs were downregulated. The most upregulated microRNAs were miR-212 and miR-2278. Prior reports have found that miR-212 is suppressed in prostate cancer. We then ran TargetScan software to find potential target mRNAs of miR-212 and miR-2278, and it predicted Lin28B mRNA as a potential target of miR-212, but not miR-2278. TargetScan also predicted that c-Myc mRNA is not a potential target of miR-212 or miR-2278. These observations suggest that Lin28B:miR-212 may work as a regulatory loop in androgen-independent prostate cancer. Furthermore, we report a predictive 2-fold symmetric model generated by the superposition of the Lin28A structure onto the I-TASSER model of Lin28B. This structural model of Lin28B suggests that it shows unique microRNA binding characteristics. Thus, if Lin28B were to bind miRNAs in a manner similar to Lin28A, conformational changes would be necessary

  16. Editors-in-Chief of Medical Journals: Are They Experts, Authorities, Both, or Neither?

    ERIC Educational Resources Information Center

    Zsindely, Sandor; Schubert, Andras

    1989-01-01

    Uses citation analysis to study the professional status and influence of the editors-in-chief of 769 medical journals. Finds that these editors-in-chief are, at least in their own specialties, not necessarily experts but authorities. (SR)

  17. EDITORIAL: Outgoing Editor-in-Chief Outgoing Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Hauptmann, Peter

    2012-01-01

    I started in 2002 as Editor-in-Chief of a well established journal—MST (Measurement Science and Technology). It was a time when modern means of communication offered new opportunities for the scientific community—for all scientists and engineers whether at universities, in industry or at other institutions—to access better quality information in a shorter time. This development helped us to be more efficient in our daily scientific work and to anticipate new trends faster than before. A flood of information was created by different search engines. A few online journals or journals published in emerging countries with a similar profile to MST appeared on the market. MST had to provide new answers in response to these developments. In 2002 I postulated two requirements to the journal. Firstly, the publisher has to be up to date. My impression over the years has been that IOPP is excellently organized. That has made it easier for the board members and all our reviewers to concentrate on the scientific aspects of our input to the journal. During all my visits to Bristol or my contacts with the IOPP staff I always met very professional and enthusiastic staff members. They have not only supported and encouraged the ideas and initiatives of the Editorial Board members, but they have also worked hard on establishing one of the most effective journal operations in the field of measurement science and technology. Many authors are well aware of this. Thus I am able to declare that the first requirement for a successful journal has been met. Secondly, the scientific level has to be high and the journal should attract readers from all over the world. This task was the responsibility of the Editorial Board members and of myself. Our strategy was on the one hand to ensure continuity in MST but on the other hand to be open to new trends and developments. Examples of these new aspects of the journal are fields like micro- and nanometrology, measurement techniques for

  18. EDITORIAL: Farewell from the outgoing Editor-in-Chief Farewell from the outgoing Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Rost, Jan Michael

    2011-01-01

    I am very pleased to announce that Professor Paul Corkum will be taking on the position of Editor-in-Chief at Journal of Physics B: Atomic, Molecular and Optical Physics (J. Phys. B) from the beginning of January 2011. During my term as Editor-in-Chief atomic, molecular and optical science has continued to change rapidly: we have seen ultracold physics widening its original emphasis on Bose-Einstein condensates to the entanglement of light and matter in the most general sense towards a science of information. At the same time attosecond science and interaction of matter with short x-ray pulses develops rapidly. I am very happy that J. Phys. B with Paul Corkum as Editor-in-Chief will play a central role in publishing exciting results from this field. I would like to thank the publishing team at J. Phys. B for their fantastic job, in particular for the quality of the refereeing system the team has been able to maintain while at the same time bringing down the publication times considerably. I thank them all for the help and support they have given me in the role of Editor-in-Chief and wish them the very best for the future. Last and certainly not least I would like to thank you, the authors, referees and readers, for the support of J. Phys. B.

  19. LIN28 expression and prognostic value in hepatocellular carcinoma patients who meet the Milan criteria and undergo hepatectomy.

    PubMed

    Qiu, Ji-Liang; Huang, Pin-Zhu; You, Jing-Hong; Zou, Ru-Hai; Wang, Li; Hong, Jian; Li, Bin-Kui; Zhou, Kai; Yuan, Yun-Fei

    2012-05-01

    Stem cell marker LIN28, related closely with SOX2 and OCT4, has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies. Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma (HCC). However, the predictive value of LIN28 in HCC outcome is still undetermined. We hypothesized that LIN28 may also play a role as a biomarker for HCC. To test this hypothesis, we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis. Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues (45.0% vs. 21.7%, P = 0.020). Moreover, LIN28 expression was significantly increased in cases with large tumor size (P = 0.010). Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival. For HCC patients who met the Milan criteria, stratified analysis revealed shorter overall survival (P = 0.007) and recurrence-free survival (P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression. Furthermore, multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival (hazard ratio= 7.093, P = 0.017) and recurrence-free survival (hazard ratio=5.518, P = 0.004) in patients who met the Milan criteria. Taken together, our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.

  20. Preparing Students To Work on Newspaper Copy Desks: Are Educators Meeting Editors' Expectations?

    ERIC Educational Resources Information Center

    Auman, Ann E.; Cook, Betsy B.

    A study surveyed two groups in the fall of 1994, journalism educators and newspaper editors. Educators completed a survey regarding the course content and skill areas emphasized in beginning level copy editing courses, while editors were asked to respond to questions regarding the skills they expect entry-level copy editors to have. Respondents…

  1. FLAn: A Free Hypermedia Editor to Create Foreign Language Learning Units

    ERIC Educational Resources Information Center

    Kilickaya, Ferit, Ed.

    2011-01-01

    Glossing words is done via special software called multimedia editors. Foreign Language Annotator (FLAn), created by Thibeault (2011), is one of these multimedia editors. FLAn (Foreign Language Annotator), a free hypermedia editor that works on both Macs and PCs, allows instructors to turn static texts into dynamic learning units by attaching…

  2. Haloalkane Dehalogenase LinB Is Responsible for β- and δ-Hexachlorocyclohexane Transformation in Sphingobium indicum B90A

    PubMed Central

    Sharma, Poonam; Raina, Vishakha; Kumari, Rekha; Malhotra, Shweta; Dogra, Charu; Kumari, Hansi; Kohler, Hans-Peter E.; Buser, Hans-Rudolf; Holliger, Christof; Lal, Rup

    2006-01-01

    Incubation of resting cells of Sphingobium indicum B90A, Sphingobium japonicum UT26, and Sphingobium francense Sp+ showed that they were able to transform β- and δ-hexachlorocyclohexane (β- and δ-HCH, respectively), the most recalcitrant hexachlorocyclohexane isomers, to pentachlorocyclohexanols, but only resting cells of strain B90A could further transform the pentachlorocyclohexanol intermediates to the corresponding tetrachlorocyclohexanediols. Moreover, experiments with resting cells of Escherichia coli expressing the LinB proteins of strains B90A, UT26, and Sp+ indicated that LinB was responsible for these transformations. Purified LinB proteins from all three strains also effected the formation of the respective pentachlorocyclohexanols. Although the three LinB enzymes differ only marginally with respect to amino acid sequence, they showed interesting differences with respect to substrate specificity. When LinB from strain B90A was incubated with β- and δ-HCH, the pentachlorocyclohexanol products were further transformed and eventually disappeared from the incubation mixtures. In contrast, the LinB proteins from strains UT26 and Sp+ could not catalyze transformation of the pentachlorocyclohexanols, and these products accumulated in the incubation mixture. A mutant of strain Sp+ lacking linA and linB did not degrade any of the HCH isomers, including β-HCH, and complementation of this mutant by linB from strain B90A restored the ability to degrade β- and δ-HCH. PMID:16957186

  3. PREFACE: Introductory remarks from the Editors Introductory remarks from the Editors

    NASA Astrophysics Data System (ADS)

    Knobloch, E.; Meseguer, A.; Marques, F.

    2012-06-01

    The local organizers of the 4th BIFD (Bifurcations and Instabilities in Fluid Dynamics) Symposium held in Barcelona on 18-21 July 2011 would like to thank the editors of Fluid Dynamics Research for offering us the opportunity of publishing a peer-reviewed special issue of the journal with a selection of the contributions presented at this conference. We thank both the authors and the referees for working with us on the rather tight schedule necessary to release the issue within one year of the date of the conference. We also thank the invited speakers, B Eckhardt, L Tuckerman, and J M Vega, for contributing keynote papers to this special issue. The series of BIFD symposia started as a small workshop in Madeira, Portugal, in 2004 with no more than 20 participants. This number increased rapidly during the second and third symposia held in 2006 (Denmark) and 2009 (United Kingdom), with 40 and 110 participants, respectively. The 4th BIFD symposium has consolidated this event as one of the leading conferences in hydrodynamic stability, with nearly 200 participants from around the world. The main goal of this conference is to bring together scientists and engineers from different disciplines directly or indirectly related to fluid dynamics, bifurcation theory and hydrodynamic stability theory. The conference covered many research areas within the aforementioned fields, ranging from thermal, shear and centrifugal flows to biofluids, films, drops, viscoelastic flows and magnetohydrodynamics. The structure of the conference, with invited plenary talks and focused sessions, helped the participants find their home in the conference and share state-of-the-art knowledge within the field of hydrodynamic instabilities. The financial support from MICINN (Spanish Ministry of Science and Innovation, Grant no FIS2009-08065-E) and UPC (Universitat Politècnica de Catalunya) is greatly appreciated. The local organizers would also like to thank ETSAB (Barcelona School of Architecture

  4. H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance

    PubMed Central

    Peng, Fei; Li, Ting-Ting; Wang, Kai-Li; Xiao, Guo-Qing; Wang, Ju-Hong; Zhao, Hai-Dong; Kang, Zhi-Jie; Fan, Wen-Jun; Zhu, Li-Li; Li, Mei; Cui, Bai; Zheng, Fei-Meng; Wang, Hong-Jiang; Lam, Eric W-F; Wang, Bo; Xu, Jie; Liu, Quentin

    2017-01-01

    Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer. PMID:28102845

  5. H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance.

    PubMed

    Peng, Fei; Li, Ting-Ting; Wang, Kai-Li; Xiao, Guo-Qing; Wang, Ju-Hong; Zhao, Hai-Dong; Kang, Zhi-Jie; Fan, Wen-Jun; Zhu, Li-Li; Li, Mei; Cui, Bai; Zheng, Fei-Meng; Wang, Hong-Jiang; Lam, Eric W-F; Wang, Bo; Xu, Jie; Liu, Quentin

    2017-01-19

    Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer.

  6. SOX2-LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors.

    PubMed

    Cimadamore, Flavio; Amador-Arjona, Alejandro; Chen, Connie; Huang, Chun-Teng; Terskikh, Alexey V

    2013-08-06

    The transcription factor SRY (sex-determining region)-box 2 (SOX2) is an important functional marker of neural precursor cells (NPCs) and plays a critical role in self-renewal and neuronal differentiation; however, the molecular mechanisms underlying its functions are poorly understood. Using human embryonic stem cell-derived NPCs to model neurogenesis, we found that SOX2 is required to maintain optimal levels of LIN28, a well-characterized suppressor of let-7 microRNA biogenesis. Exogenous LIN28 expression rescued the NPC proliferation deficit, as well as the early but not the late stages of the neurogenic deficit associated with the loss of SOX2. We found that SOX2 binds to a proximal site in the LIN28 promoter region and regulates LIN28 promoter acetylation, likely through interactions with the histone acetyltransferase complex. Misexpression of let-7 microRNAs in NPCs reduced proliferation and inhibited neuronal differentiation, phenocopying the loss of SOX2. In particular, we identified let-7i as a novel and potent inhibitor of neuronal differentiation that targets MASH1 and NGN1, two well-characterized proneural genes. In conclusion, we discovered the SOX2-LIN28/let-7 pathway as a unique molecular mechanism governing NPC proliferation and neurogenic potential.

  7. SOX2–LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors

    PubMed Central

    Cimadamore, Flavio; Amador-Arjona, Alejandro; Chen, Connie; Huang, Chun-Teng; Terskikh, Alexey V.

    2013-01-01

    The transcription factor SRY (sex-determining region)-box 2 (SOX2) is an important functional marker of neural precursor cells (NPCs) and plays a critical role in self-renewal and neuronal differentiation; however, the molecular mechanisms underlying its functions are poorly understood. Using human embryonic stem cell-derived NPCs to model neurogenesis, we found that SOX2 is required to maintain optimal levels of LIN28, a well-characterized suppressor of let-7 microRNA biogenesis. Exogenous LIN28 expression rescued the NPC proliferation deficit, as well as the early but not the late stages of the neurogenic deficit associated with the loss of SOX2. We found that SOX2 binds to a proximal site in the LIN28 promoter region and regulates LIN28 promoter acetylation, likely through interactions with the histone acetyltransferase complex. Misexpression of let-7 microRNAs in NPCs reduced proliferation and inhibited neuronal differentiation, phenocopying the loss of SOX2. In particular, we identified let-7i as a novel and potent inhibitor of neuronal differentiation that targets MASH1 and NGN1, two well-characterized proneural genes. In conclusion, we discovered the SOX2–LIN28/let-7 pathway as a unique molecular mechanism governing NPC proliferation and neurogenic potential. PMID:23884650

  8. Bistable switch in let-7 miRNA biogenesis pathway involving Lin28.

    PubMed

    Shi, Fei; Yu, Wenbao; Wang, Xia

    2014-10-21

    miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppressor function depending on their levels of expression. To explore the physiological significance of let-7 in regulating cell fate decisions, we present a coarse grained model of let-7 biogenesis network, in which let-7 and its regulator Lin28 inhibit mutually. The dynamics of this minimal network architecture indicates that, as the concentration of Lin28 increases, the system undergoes a transition from monostability to a bistability and then to a one-way switch with increasing strength of positive feedback of let-7, while in the absence of Lin28 inhibition, the system loses bistability. Moreover, the ratio of degradation rates of let-7 and Lin28 is critical for the switching sensitivity and resistance to stimulus fluctuations. These findings may highlight why let-7 is required for normal gene expression in the context of embryonic development and oncogenesis, which will facilitate the development of approaches to exploit this regulatory pathway by manipulating Lin28/let-7 axis for novel treatments of human diseases.

  9. Molecular basis for interaction of let-7 microRNAs with Lin28

    PubMed Central

    Nam, Yunsun; Chen, Casandra; Gregory, Richard I; Chou, James J; Sliz, Piotr

    2011-01-01

    SUMMARY MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. Among these, members of the let-7 miRNA family control many cell fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, post-transcriptional inhibitor of let-7 biogenesis. We report crystal structures of mouse Lin28 in complex with sequences from let-7d, let-7-f1, and let-7g precursors. The two folded domains of Lin28 recognize two distinct regions of the RNA and are sufficient for inhibition of let-7 in vivo. We also show by NMR spectroscopy that the linker connecting the two folded domains is flexible, accommodating Lin28 binding to diverse let-7 family members. Protein-RNA complex formation imposes specific conformations on both components that could affect downstream recognition by other processing factors. Our data provide a molecular explanation for Lin28 specificity and a model for how it regulates let-7. PMID:22078496

  10. Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis

    PubMed Central

    2011-01-01

    Background A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. Results The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. Conclusions With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites. PMID:21266047

  11. Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis.

    PubMed

    Nemoto, Kiyotaka; Dan, Ippeita; Rorden, Christopher; Ohnishi, Takashi; Tsuzuki, Daisuke; Okamoto, Masako; Yamashita, Fumio; Asada, Takashi

    2011-01-25

    A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites.

  12. Lin28-let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras

    SciTech Connect

    Oh, Jee-Sun.; Kim, Jae-Jin; Byun, Ju-Yeon; Kim, In-Ah

    2010-01-15

    Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling. Methods and Materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed. Results: The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression and radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach. Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.

  13. νLIN6: An Integrated Mobility Protocol in IPv6

    NASA Astrophysics Data System (ADS)

    Banno, Ayumi; Teraoka, Fumio

    This paper proposes a protocol called νLIN6 which supports both network mobility and host mobility in IPv6. There are several proposals to support network mobility and host mobility. Network Mobility (NEMO) Basic Support Protocol has several problems such as pinball routing, large header overhead due to multiple levels of tunneling, and a single point of failure. Optimized NEMO (ONEMO) and Mobile IP with Address Translation (MAT) are solutions to provide route optimization, but they generate a lot of signaling messages at a handover. In νLIN6, packet relay is required only once regardless of the nested level in network mobility while optimal routing is always provided in host mobility. A fixedsized extension header is used in network mobility while there is no header overhead in host mobility. νLIN6 is more tolerant of network failure and mobility agent failure than NEMO Basic Support Protocol. It also allows ordinary IPv6 nodes to communicate with mobile nodes and nodes in the mobile network. We implemented νLIN6 on NetBSD 2.0 Release. Our measurement results showed νLIN6 can provide host mobility and network mobility with low overhead.

  14. Wysession begins term as Eos Section Editor for Seismology

    NASA Astrophysics Data System (ADS)

    Wysession, Michael

    In mid-April, Michael Wysession, an associate professor in the Department of Earth and Planetary Sciences at Washington University, embarked on a 3-year term as section editor of Eos for seismology. Wysession brings to the position a strong background in research and teaching. Below are a few remarks from Wysession.“I recently became the new seismology editor for Eos. I look forward to presenting the many exciting areas of seismological research to the entire geophysical community. I have taught at Washington University since obtaining my Ph.D. at Northwestern University in 1991. My interest in seismology began during my undergraduate years at Brown University (Sc.B., 1984), but my experience as an educator began after I graduated and taught high school math and physics in Staten Island, N.Y.

  15. William E. Edmonston, Jr.: Editor, 1968-1976.

    PubMed

    Kihlstrom, John F; Frischholz, Edward J

    2010-10-01

    This article is part of an occasional series profiling editors of the American Journal of Clinical Hypnosis (AJCH). William E. Edmonston was the second editor, succeeding Milton H. Erickson. His research focused on the use of conditioning paradigms and psychophysiological measures to explore a wide variety of hypnotic phenomena, leading to a "neo-Pavlovian" theory of neutral hypnosis as physiological relaxation (anesis). A longtime professor of psychology at Colgate University, he created an interdisciplinary undergraduate major in neuroscience, and was named New York State College Professor of the Year in 1988. He gave the Journal a new look, and a greater balance of clinical and experimental papers. The article also provides background on George Barton Cutten, George H. Estabrooks, and Frank A. Pattie, pioneers of hypnosis who were linked to Edmonston.

  16. From the desk of the Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Hei, Tom K.

    2015-07-01

    Life Sciences in Space Research had a prominent presence at the International Congress of Radiation Research (ICRR) meeting held in Kyoto, Japan from May 25th-29th, with seven of the eleven editors attending the meeting. A journal booth was also put up at the pre-ICRR satellite meeting on Space Radiation and Heavy Ions in Therapy (SRHITS) held a few days earlier in Osaka. Since the inception of LSSR last year, the editors and publisher have promoted the journal at a number of major conferences including COSPAR 2014 in Moscow, the annual meeting of the Radiation Research Society and the NASA Space Radiation Investigators Meeting. These efforts have increased awareness of the journal among investigators in space life sciences and related fields. The number of monthly downloads of articles from the journal website averages 2000, a respectable number for a brand new journal.

  17. Space Weather Editors in Transition: Hail and Farewell

    NASA Astrophysics Data System (ADS)

    Knipp, Delores J.

    2017-02-01

    I hope you will join me in welcoming Dr. Daniel Welling of University of Michigan and Dr. T. Paul O'Brien of the Aerospace Corporation to the Space Weather (SWE) editorial team. Dan and Paul have answered the call to fill the shoes of two departing editors: Dr. Howard Singer and Dr. Barbara Giles. Dan brings insight related to space weather model development, while Paul brings expertise in the geospace radiation environment.

  18. Towards a document structure editor for software requirements analysis

    NASA Technical Reports Server (NTRS)

    Kowalski, Vincent J.; Lekkos, Anthony A.

    1986-01-01

    Of the six or seven phases of the software engineering life cycle, requirements analysis tends to be the least understood and the least formalized. Correspondingly, a scarcity of useful software tools exist which aid in the development of user and system requirements. It is proposed that requirements analysis should culminate in a set of documents similar to those that usually accompany a delivered Software product. The design of a software tool, the Document Structure Editor, which facilitates the development of such documentation.

  19. JGR-Solid Earth and Planets GP editor appointed

    NASA Astrophysics Data System (ADS)

    Ken Hoffman (Physics Department, California Polytechnic State University, San Luis Obispo) has been appointed GP editor for papers submitted to the Journal of Geophysical Research—Solid Earth and Planets. His tenure will be from January 1987 to December 1988. Hoffman holds a Ph.D. in geophysics from the University of California, Berkeley, and has published extensively in the areas of rock magnetism, paleomagnetism, lunar paleointensity, and most recently, geomagnetic dipole field reversal modeling.

  20. Incremental Expression Parsing for Syntax-Directed Editors

    DTIC Science & Technology

    1982-10-27

    Cretsna*refr a+b+cde ftth I / \\ ,:I \\ I’\\ / , I \\ b- ’ I I € d Figure 4-3: Correct syntax tree for"a + (b + c" d" e) ftgth" The tokens between, the...Schwartz. The Design of a Language-Directed Editor for Block-Structured Languages. In Proceedings of the ACM SIGPLAN SIGOA Symposium on Text Manipulation

  1. The STAGING Text Editor/Data Base Loader Program Manual.

    DTIC Science & Technology

    1980-05-01

    editor and the loader require the library DATAMAN which contains the lowest level data base subroutines used by STAGING. All necessary programs and...LDSETLIB=EDITLB/ DATAMAN . LISLOADEDITLDEDIT. LIBLOADEDITLBRENARK. NOGOED. CATALOGED,1 DCAHKPUxXRXR2XR. RETURNEDITLB,EDDATAMAN. REVERT. UPDATING THE DATA...library DATAMAN to properly position COMMON areas. The libraries SUPLIB and GENERLB contain successively higher level data base manipulation subroutines

  2. Reference Accuracy: Authors', Reviewers', Editors', and Publishers' Contributions

    PubMed Central

    2014-01-01

    Scientific authors are responsible for the accuracy of their writings and references to others' works. However, relying on authors is not enough when it comes to processing their manuscripts. Joint efforts of authors, peer reviewers, editors, and publishers throughout the publishing process may prevent most reference errors. This article analyzes essential aspects of bibliographic management and focuses on the importance of validating references by all stakeholders of scholarly publishing. PMID:25469055

  3. Statement on Publication Ethics for Editors and Publishers.

    PubMed

    Gasparyan, Armen Yuri; Yessirkepov, Marlen; Voronov, Alexander A; Gorin, Sergey V; Koroleva, Anna M; Kitas, George D

    2016-09-01

    The digitization and related developments in journal editing and publishing necessitate increasing the awareness of all stakeholders of science communication in the emerging global problems and possible solutions. Journal editors and publishers are frequently encountered with the fast-growing problems of authorship, conflicts of interest, peer review, research misconduct, unethical citations, and inappropriate journal impact metrics. While the number of erroneous and unethical research papers and wasteful, or 'predatory', journals is increasing exponentially, responsible editors are urged to 'clean' the literature by correcting or retracting related articles. Indexers are advised to implement measures for accepting truly influential and ethical journals and delisting sources with predatory publishing practices. Updating knowledge and skills of authors, editors and publishers, developing and endorsing recommendations of global editorial associations, and (re)drafting journal instructions can be viewed as potential tools for improving ethics of academic journals. The aim of this Statement is to increase awareness of all stakeholders of science communication of the emerging ethical issues in journal editing and publishing and initiate a campaign of upgrading and enforcing related journal instructions.

  4. Authors, editors, and the signs, symptoms and causes of plagiarism

    PubMed Central

    Shashok, Karen

    2011-01-01

    Plagiarism and inadequate citing appear to have reached epidemic proportions in research publication. This article discusses how plagiarism is defined and suggests some possible causes for the increase in the plagiarism disease. Most editors do not have much tolerance for text re-use with inadequate citation regardless of reasons why words are copied from other sources without correct attribution. However, there is now some awareness that re-use of words in research articles to improve the writing or “the English” (which has become a common practice) should be distinguished from intentional deceit for the purpose of stealing other authors’ ideas (which appears to remain a very rare practice). Although it has become almost as easy for editors to detect duplicate text as it is for authors to re-use text from other sources, editors often fail to consider the reasons why researchers resort to this strategy, and tend to consider any text duplication as a symptom of serious misconduct. As a result, some authors may be stigmatized unfairly by being labeled as plagiarists. The article concludes with practical advice for researchers on how to improve their writing and citing skills and thus avoid accusations of plagiarism. PMID:21957412

  5. A perspective on computer documentation: System developer vs. technical editor

    SciTech Connect

    Carnes, E.T.; Truett, L.F.

    1995-12-31

    Between the computer-knowledgeable {open_quotes}techie{close_quotes} and the technical writer is a chasm created by differences in knowledge bases and skills. Although this gap is widened by misunderstandings and misconceptions of system development roles, it is bridged by mutual need and dual appreciation. Often the editor/writer is {open_quotes}behind{close_quotes} from beginning to end. The writer normally joins the team after the programmers are well into system development and do not want to {open_quotes}waste time{close_quotes} discussing fundamentals. The writer is usually excluded from technical discussions because it is assumed that he/she would not understand anyway. Later in the system development cycle, the writer has no time to polish the documentation before a new version of the software is issued which implies that the documentation must be revised. Nevertheless, the editor/writer`s product is critical for the end-user`s appreciation of the software, a fact which promotes unity to complete the comprehensive package of software and documentation. This paper explores the planks in the bridge that spans the chasm between developers and their fundamental PR agents, the technical editors/writers. This paper defines approaches (e.g., The Circling Theory) and techniques (Bold Thrust!) employed for effective communication -- between software developer and technical writer as well as between the software and the end-user.

  6. EDITORIAL: Farewell from the outgoing Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Burnett, Keith

    2005-01-01

    I am very pleased to announce that Professor Jan-Michael Rost will be taking on the position of Editor-in-Chief at Journal of Physics B: Atomic, Molecular and Optical Physics (J. Phys. B) from the beginning of January 2005. As Editor-in-Chief I have seen the journal respond to the rapid and exciting developments in atomic, molecular and optical physics of recent years. There will, I am sure, be a great deal of new and important science in our field in the years ahead. I am also sure that Jan-Michael will do a fantastic job in guiding the journal through these times. The publishing team at J. Phys. B is a superbly responsive and effective one that does a great job in publishing the science we do. I want to thank them all for the help and support they have given me in the role of Editor-in-Chief and wish them the very best for the future. Last and certainly not least I would like to thank you, the authors, referees and readers, for making J. Phys. B such a great journal to have been a part of.

  7. CMS Configuration Editor: GUI based application for user analysis job

    NASA Astrophysics Data System (ADS)

    de Cosa, A.

    2011-12-01

    We present the user interface and the software architecture of the Configuration Editor for the CMS experiment. The analysis workflow is organized in a modular way integrated within the CMS framework that organizes in a flexible way user analysis code. The Python scripting language is adopted to define the job configuration that drives the analysis workflow. It could be a challenging task for users, especially for newcomers, to develop analysis jobs managing the configuration of many required modules. For this reason a graphical tool has been conceived in order to edit and inspect configuration files. A set of common analysis tools defined in the CMS Physics Analysis Toolkit (PAT) can be steered and configured using the Config Editor. A user-defined analysis workflow can be produced starting from a standard configuration file, applying and configuring PAT tools according to the specific user requirements. CMS users can adopt this tool, the Config Editor, to create their analysis visualizing in real time which are the effects of their actions. They can visualize the structure of their configuration, look at the modules included in the workflow, inspect the dependences existing among the modules and check the data flow. They can visualize at which values parameters are set and change them according to what is required by their analysis task. The integration of common tools in the GUI needed to adopt an object-oriented structure in the Python definition of the PAT tools and the definition of a layer of abstraction from which all PAT tools inherit.

  8. An editor's considerations in publishing industry-sponsored studies.

    PubMed

    Droller, Michael J

    2015-03-01

    The fundamental responsibility of a journal editor is to assure that studies accepted for publication provide rigorous original scientific information and reviews that are considered important to the readership. The fundamental requirements of such reports from an editor's perspective include objectivity and transparency in each of the study design, implementation of investigation methods, acquisition of data, inclusive analysis and interpretation of results, appropriate application of statistical methods, presentation of outcomes in the context of a balanced and comprehensive review of relevant literature, and meaningful conclusions. In proceeding on these presumptions, editors then have the responsibility of obtaining rigorous, objective, and constructive reviews of these reports so that they can make an unbiased decision regarding their disposition. The fundamental objective in this is to enhance the ultimate scientific validity and value of the work if and when it is accepted for publication. Guidelines have been advanced by several organizations to identify how such editorial responsibilities can be fulfilled. These guidelines also pertain to investigators, authors, and sponsors of the studies, which the various reports and reviews describe. The present article reviews these guidelines as they relate to both industry-sponsored and investigator-initiated investigations and as relevant to the variety of reports that a scientific/medical journal such as Urologic Oncology: Seminars and Original Investigations receives for publication.

  9. Statement on Publication Ethics for Editors and Publishers

    PubMed Central

    2016-01-01

    The digitization and related developments in journal editing and publishing necessitate increasing the awareness of all stakeholders of science communication in the emerging global problems and possible solutions. Journal editors and publishers are frequently encountered with the fast-growing problems of authorship, conflicts of interest, peer review, research misconduct, unethical citations, and inappropriate journal impact metrics. While the number of erroneous and unethical research papers and wasteful, or 'predatory', journals is increasing exponentially, responsible editors are urged to 'clean' the literature by correcting or retracting related articles. Indexers are advised to implement measures for accepting truly influential and ethical journals and delisting sources with predatory publishing practices. Updating knowledge and skills of authors, editors and publishers, developing and endorsing recommendations of global editorial associations, and (re)drafting journal instructions can be viewed as potential tools for improving ethics of academic journals. The aim of this Statement is to increase awareness of all stakeholders of science communication of the emerging ethical issues in journal editing and publishing and initiate a campaign of upgrading and enforcing related journal instructions. PMID:27510376

  10. Lin28a protects against postinfarction myocardial remodeling and dysfunction through Sirt1 activation and autophagy enhancement.

    PubMed

    Hao, Yuanyuan; Lu, Qun; Yang, Guodong; Ma, Aiqun

    2016-10-28

    Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury. Lin28a significantly inhibited left ventricular remodeling and cardiac dysfunction after MI, as demonstrated via echocardiography and hemodynamic measurements. Lin28a reduced cardiac enzyme and inflammatory marker release in mice subjected to MI-induced injury. The mechanisms underlying the protective effects of Lin28a against MI-induced injury were associated with autophagy enhancements and apoptosis inhibition. Consistent with these findings, Lin28a knockdown aggravated cardiac remodeling and dysfunction after MI-induced injury. Lin28a knockdown also inhibited cardiomyocyte autophagy and increased cardiomyocyte apoptosis in mice subjected to MI-induced injury. Interestingly, Sirt1 knockdown abolished the protective effects of Lin28a against cardiac remodeling and dysfunction after MI, and Lin28a failed to increase the numbers of GFP-LC3-positive punctae and decrease aggresome and p62 accumulation in Sirt1-knockdown neonatal cardiomyocytes subjected to hypoxia-induced injury. Lin28a inhibits cardiac remodeling, improves cardiac function, and reduces cardiac enzyme and inflammatory marker release after MI. Lin28a also up-regulates cardiomyocyte autophagy and inhibits cardiomyocyte apoptosis through Sirt1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. LIN28 is selectively expressed by primordial and pre-meiotic germ cells in the human fetal ovary.

    PubMed

    Childs, Andrew J; Kinnell, Hazel L; He, Jing; Anderson, Richard A

    2012-09-01

    Germ cell development requires timely transition from primordial germ cell (PGC) self-renewal to meiotic differentiation. This is associated with widespread changes in gene expression, including downregulation of stem cell-associated genes, such as OCT4 and KIT, and upregulation of markers of germ cell differentiation and meiosis, such as VASA, STRA8, and SYCP3. The stem cell-expressed RNA-binding protein Lin28 has recently been demonstrated to be essential for PGC specification in mice, and LIN28 is expressed in human germ cell tumors with phenotypic similarities to human fetal germ cells. We have therefore examined the expression of LIN28 during normal germ cell development in the human fetal ovary, from the PGC stage, through meiosis to the initiation of follicle formation. LIN28 transcript levels were highest when the gonad contained only PGCs, and decreased significantly with increasing gestation, coincident with the onset of germ cell differentiation. Immunohistochemistry revealed LIN28 protein expression to be germ cell-specific at all stages examined. All PGCs expressed LIN28, but at later gestations expression was restricted to a subpopulation of germ cells, which we demonstrate to be primordial and premeiotic germ cells based on immunofluorescent colocalization of LIN28 and OCT4, and absence of overlap with the meiosis marker SYCP3. We also demonstrate the expression of the LIN28 target precursor pri-microRNA transcripts pri-LET7a/f/d and pri-LET-7g in the human fetal ovary, and that expression of these is highest at the PGC stage, mirroring that of LIN28. The spatial and temporal restriction of LIN28 expression and coincident peaks of expression of LIN28 and target pri-microRNAs suggest important roles for this protein in the maintenance of the germline stem cell state and the regulation of microRNA activity in the developing human ovary.

  12. Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors.

    PubMed

    Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

    2014-04-01

    Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis.

  13. Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors

    PubMed Central

    Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

    2014-01-01

    Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis. PMID:24452802

  14. GENII-LIN: a new object-oriented interface for the GENII code.

    PubMed

    Sumini, M; Teodori, F; Cantoro, N

    2005-01-01

    GENII-LIN is a new object-oriented interface for GENII, a well-known analysis tool for the health impact evaluation of accidental or chronic release of radionuclides to the environment. GENII-LIN has been developed under the Linux OS, chosen because it is a stable, reliable and open source. The suite codes that constitute the original GENII simulation kernel have been re-implemented and built, using the G77, the Fortran 77 module of the GCC collection. The code modules and the flow of data among them are at present fully controlled by a management interface written in C++, which is the core of the package. GENII-LIN comes with a new graphical user interface (GUI), built using the QT libraries by Trolltech. Through the wizard-like GUI, the user has full control over the code and can easily handle both the input and the output files.

  15. Similarity of the C. elegans developmental timing protein LIN-42 to circadian rhythm proteins.

    PubMed

    Jeon, M; Gardner, H F; Miller, E A; Deshler, J; Rougvie, A E

    1999-11-05

    The Caenorhabditis elegans heterochronic genes control the relative timing and sequence of many events during postembryonic development, including the terminal differentiation of the lateral hypodermis, which occurs during the final (fourth) molt. Inactivation of the heterochronic gene lin-42 causes hypodermal terminal differentiation to occur precociously, during the third molt. LIN-42 most closely resembles the Period family of proteins from Drosophila and other organisms, proteins that function in another type of biological timing mechanism: the timing of circadian rhythms. Per mRNA levels oscillate with an approximately 24-hour periodicity. lin-42 mRNA levels also oscillate, but with a faster rhythm; the oscillation occurs relative to the approximately 6-hour molting cycles of postembryonic development.

  16. PDB Editor: a user-friendly Java-based Protein Data Bank file editor with a GUI.

    PubMed

    Lee, Jonas; Kim, Sung Hou

    2009-04-01

    The Protein Data Bank file format is the format most widely used by protein crystallographers and biologists to disseminate and manipulate protein structures. Despite this, there are few user-friendly software packages available to efficiently edit and extract raw information from PDB files. This limitation often leads to many protein crystallographers wasting significant time manually editing PDB files. PDB Editor, written in Java Swing GUI, allows the user to selectively search, select, extract and edit information in parallel. Furthermore, the program is a stand-alone application written in Java which frees users from the hassles associated with platform/operating system-dependent installation and usage. PDB Editor can be downloaded from http://sourceforge.net/projects/pdbeditorjl/.

  17. The XML Metadata Editor of GFZ Data Services

    NASA Astrophysics Data System (ADS)

    Ulbricht, Damian; Elger, Kirsten; Tesei, Telemaco; Trippanera, Daniele

    2017-04-01

    Following the FAIR data principles, research data should be Findable, Accessible, Interoperable and Reuseable. Publishing data under these principles requires to assign persistent identifiers to the data and to generate rich machine-actionable metadata. To increase the interoperability, metadata should include shared vocabularies and crosslink the newly published (meta)data and related material. However, structured metadata formats tend to be complex and are not intended to be generated by individual scientists. Software solutions are needed that support scientists in providing metadata describing their data. To facilitate data publication activities of 'GFZ Data Services', we programmed an XML metadata editor that assists scientists to create metadata in different schemata popular in the earth sciences (ISO19115, DIF, DataCite), while being at the same time usable by and understandable for scientists. Emphasis is placed on removing barriers, in particular the editor is publicly available on the internet without registration [1] and the scientists are not requested to provide information that may be generated automatically (e.g. the URL of a specific licence or the contact information of the metadata distributor). Metadata are stored in browser cookies and a copy can be saved to the local hard disk. To improve usability, form fields are translated into the scientific language, e.g. 'creators' of the DataCite schema are called 'authors'. To assist filling in the form, we make use of drop down menus for small vocabulary lists and offer a search facility for large thesauri. Explanations to form fields and definitions of vocabulary terms are provided in pop-up windows and a full documentation is available for download via the help menu. In addition, multiple geospatial references can be entered via an interactive mapping tool, which helps to minimize problems with different conventions to provide latitudes and longitudes. Currently, we are extending the metadata editor

  18. Lin28A induces energetic switching to glycolytic metabolism in human embryonic kidney cells.

    PubMed

    Docherty, Craig K; Salt, Ian P; Mercer, John R

    2016-05-26

    Loss of a cell's capacity to generate sufficient energy for cellular functions is a key hallmark of the ageing process and ultimately leads to a variety of important age-related pathologies such as cancer, Parkinson's disease and atherosclerosis. Regenerative medicine has sought to reverse these pathologies by reprogramming somatic cells to a more juvenile energetic state using a variety of stem cell factors. One of these factors, Lin28, is considered a candidate for modification in the reprogramming of cellular energetics to ameliorate the ageing process while retaining cell phenotype. Over-expression of Lin28A resulted in key changes to cellular metabolism not observed in wild-type controls. Extracellular pH flux analysis indicated that Lin28A over expression significantly increased the rate of glycolysis, whilst high resolution oxygen respirometry demonstrated a reduced oxygen consumption. Western blot and real-time PCR analysis identified Hexokinase II as one of the key modulators of glycolysis in these cells which was further confirmed by increased glucose transport. A metabolic switching effect was further emphasised by Western blot analysis where the oxygen consuming mitochondrial complex IV was significantly reduced after Lin28A over expression. Results from this study confirm that Lin28A expression promotes metabolic switching to a phenotype that relies predominantly on glycolysis as an energy source, while compromising oxidative phosphorylation. Mechanisms to augment regulated Lin28A in age related pathologies that are characterised by mitochondria dysfunction or in differentiated and aged post-mitotic cells is the future goal of this work.

  19. Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway.

    PubMed

    Faehnle, Christopher R; Walleshauser, Jack; Joshua-Tor, Leemor

    2014-10-09

    The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development, glucose metabolism and tissue regeneration. Overexpression of Lin28 is correlated with the onset of numerous cancers, whereas let-7, a tumour suppressor, silences several human oncogenes. Lin28 binds to precursor let-7 (pre-let-7) hairpins, triggering the 3' oligo-uridylation activity of TUT4 and TUT7 (refs 10-12). The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13, 14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2 substrate recognition we determined the structure of mouse Dis3l2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from that of its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3l2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway.

  20. LIN28 Expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels.

    PubMed

    Murray, Matthew J; Saini, Harpreet K; Siegler, Charlotte A; Hanning, Jennifer E; Barker, Emily M; van Dongen, Stijn; Ward, Dawn M; Raby, Katie L; Groves, Ian J; Scarpini, Cinzia G; Pett, Mark R; Thornton, Claire M; Enright, Anton J; Nicholson, James C; Coleman, Nicholas

    2013-08-01

    Despite their clinicopathologic heterogeneity, malignant germ cell tumors (GCT) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of downregulation of the let-7 family of tumor suppressor microRNAs in malignant GCTs. Microarray results from pediatric and adult samples (n = 45) showed that LIN28, the negative regulator of let-7 biogenesis, was abundant in malignant GCTs, regardless of patient age, tumor site, or histologic subtype. Indeed, a strong negative correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, as the sequence complementary to the 2 to 7 nt common let-7 seed "GAGGUA" was enriched in the 3' untranslated regions of mRNAs upregulated in pediatric and adult malignant GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were upregulated in malignant GCT cells, confirming significant negative correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by quantitative reverse transcription PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67, and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and downregulate MYCN, AURKB, and LIN28, the latter via a double-negative feedback loop. We conclude that the LIN28/let-7 pathway has a critical pathobiologic role in malignant GCTs and therefore offers a promising target for therapeutic intervention. ©2013 AACR.

  1. Mechanism of Dis3L2 substrate recognition in the Lin28/let-7 pathway

    PubMed Central

    Joshua-Tor, Leemor

    2014-01-01

    Summary paragraph The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs1–4. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development5, glucose metabolism6 and tissue regeneration7. Alternatively, Lin28 overexpression is correlated with the onset of numerous cancers8, while let-7, a tumor suppressor, silences several human oncogenes5. Lin28 binds to precursor let-7 (pre-let-7) hairpins9, triggering the 3' oligo-uridylation activity of TUT4/710–12. The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3L213,14, a homolog of the catalytic subunit of the RNA exosome. The molecular basis of Lin28 mediated recruitment of TUT4/7 to pre-let-7 and its subsequent degradation by Dis3L2 is largely unknown. To examine the mechanism of Dis3L2 substrate recognition we determined the structure of mouse Dis3L2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first twelve nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3L2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28/let-7 pathway. PMID:25119025

  2. The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy.

    PubMed

    Lozoya, Teresa; Domínguez, Francisco; Romero-Ruiz, Antonio; Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

    2014-01-01

    Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7-9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤ 6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤ 6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans.

  3. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6

    PubMed Central

    2014-01-01

    Background Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. Results We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. Conclusions These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39

  4. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

    PubMed

    Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

    2014-05-13

    Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

  5. [Professor LIN Guohua's experience of gold implantation at acupoint for rheumatoid arthritis].

    PubMed

    Li, Jingjing; Pei, Wenya

    2015-12-01

    Based on the pathogenesis and symptom of rheumatoid arthritis (RA), professor LIN Guohua's unique opinion and method for RA in clinical treatment are summarized and analyzed. In the opinion of Professor Lin, RA is considered as "Jinbi" and "Gubi" in TCM, which is caused by deficient root with superficial excess. Based on the symptoms of RA, attention should be focused on lung-kidney diagnosis and treatment, and gold and catgut implantation at acupoint can be mutually combined, which is aimed to provide a special and effective method for clinical treatment of RA.

  6. Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of let-7a in breast cancer cells.

    PubMed

    Liu, Yujie; Li, Haiyan; Feng, Juan; Cui, Xiuying; Huang, Wei; Li, Yudong; Su, Fengxi; Liu, Qiang; Zhu, Jiujun; Lv, Xiaobin; Chen, Jianing; Huang, Di; Yu, Fengyan

    2013-01-01

    The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis.

  7. Lin28 Induces Epithelial-to-Mesenchymal Transition and Stemness via Downregulation of Let-7a in Breast Cancer Cells

    PubMed Central

    Huang, Wei; Li, Yudong; Su, Fengxi; Liu, Qiang; Zhu, Jiujun; Lv, Xiaobin; Chen, Jianing; Huang, Di; Yu, Fengyan

    2013-01-01

    The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis. PMID:24349438

  8. A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C. elegans

    PubMed Central

    Srinivasan, Dayalan G.; Fisk, Ridgely M.; Xu, Huihong; van den Heuvel, Sander

    2003-01-01

    The Caenorhabditis elegans coiled-coil protein LIN-5 mediates several processes in cell division that depend on spindle forces, including alignment and segregation of chromosomes and positioning of the spindle. Here, we describe two closely related proteins, GPR-1 and GPR-2 (Gprotein regulator), which associate with LIN-5 in vivo and in vitro and depend on LIN-5 for localization to the spindle and cell cortex. GPR-1/GPR-2 contain a GoLoco/GPR motif that mediates interaction with GDP-bound Gαi/o. Inactivation of lin-5, gpr-1/gpr-2, or the Gαi/o genes goa-1 and gpa-16 all cause highly similar chromosome segregation and spindle positioning defects, indicating a positive role for the LIN-5 and GPR proteins in G protein signaling. The lin-5 and gpr-1/gpr-2 genes appear to act downstream of the par polarity genes in the one- and two-cell stages and downstream of the tyrosine kinase-related genes mes-1 and src-1 at the four-cell stage. Together, these results indicate that GPR-1/GPR-2 in association with LIN-5 activate G protein signaling to affect spindle force. Polarity determinants may regulate LIN-5/GPR/Gα locally to create the asymmetric forces that drive spindle movement. Results in C. elegans and other species are consistent with a novel model for receptor-independent activation of Gαi/o signaling. PMID:12730122

  9. LIN9, a subunit of the DREAM complex, regulates mitotic gene expression and proliferation of embryonic stem cells.

    PubMed

    Esterlechner, Jasmina; Reichert, Nina; Iltzsche, Fabian; Krause, Michael; Finkernagel, Florian; Gaubatz, Stefan

    2013-01-01

    The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vitro. In this study we examined the effect of knocking down LIN9 on ESCs. We demonstrate that depletion of LIN9 alters the cell cycle distribution of ESCs and results in an accumulation of cells in G2 and M and in an increase of polyploid cells. Genome-wide expression studies showed that the depletion of LIN9 results in downregulation of mitotic genes and in upregulation of differentiation-specific genes. ChIP-on chip experiments showed that mitotic genes are direct targets of LIN9 while lineage specific markers are regulated indirectly. Importantly, depletion of LIN9 does not alter the expression of pluripotency markers SOX2, OCT4 and Nanog and LIN9 depleted ESCs retain alkaline phosphatase activity. We conclude that LIN9 is essential for proliferation and genome stability of ESCs by activating genes with important functions in mitosis and cytokinesis.

  10. Greetings from the new Editor-in-Chief, Ronald Stambaugh Greetings from the new Editor-in-Chief, Ronald Stambaugh

    NASA Astrophysics Data System (ADS)

    Stambaugh, Ronald

    2012-04-01

    I am very pleased to join the outstanding leadership team for the journal Nuclear Fusion as Scientific Editor. The journal's high position in the field of fusion energy research derives in no small measure from the efforts of the IAEA team in Vienna, the production and marketing of IOP Publishing, the Board of Editors led by its chairman Mitsuru Kikuchi, the Associate Editor for Inertial Confinement Max Tabak and the outgoing Scientific Editor, Paul Thomas. During Paul's five year tenure submissions have grown by over 40%. The usage of the electronic journal has grown year by year with about 300 000 full text downloads of Nuclear Fusion articles in 2011, an impressive figure due in part to the launch of the full 50 year archive. High quality has been maintained while times for peer review and publishing have been reduced and the journal achieved some of the highest impact factors ever (as high as 4.27). The journal has contributed greatly to building the international scientific basis for fusion. I was privileged to serve from 2003 to 2010 as chairman of the Coordinating Committee for the International Tokamak Physics Activity (ITPA) which published in Nuclear Fusion the first ITER Physics Basis (1999) and its later update (2007). The scientific basis that has been developed to date for fusion has led to the construction of major facilities to demonstrate the production of power-plant relevant levels of fusion reactions. We look forward to the journal continuing to play a key role in the international effort toward fusion energy as these exciting major facilities and the various approaches to fusion continue to be developed. It is clear that Nuclear Fusion maintains its position in the field because of the perceived high quality of the submissions, the refereeing and the editorial processes, and the availability and utility of the online journal. The creation of the Nuclear Fusion Prize, led by the Board of Editors chairman Mitsuru Kikuchi, for the most outstanding

  11. Lin28 Mediates Paclitaxel Resistance by Modulating p21, Rb and Let-7a miRNA in Breast Cancer Cells

    PubMed Central

    Lv, Kezhen; Liu, Liqun; Wang, Linbo; Yu, Jiren; Liu, Xiaojiao; Cheng, Yongxia; Dong, Minjun; Teng, Rongyue; Wu, Linjiao; Fu, Peifen; Deng, Wuguo; Hu, Wenxian; Teng, Lisong

    2012-01-01

    Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemoresistance remained unknown. In this study, we investigated the association of Lin28 with paclitaxel resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines and tumor tissues. We found that the expression level of Lin28 was closely associated with the resistance to paclitaxel treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to paclitaxel than the MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which had low-level expression of Lin28. Knocking down of Lin28 in Lin28 high expression T47D cells increased the sensitivity to paclitaxel treatment, while stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to paclitaxel treatment, resulting in a significant increase of IC50 values of paclitaxel. Transfection with Lin28 also significantly inhibited paclitaxel-induced apoptosis. We also found that Lin28 expression was dramatically increased in tumor tissues after neoadjuvant chemotherapy or in local relapse or metastatic breast cancer tissues. Moreover, further studies showed that p21, Rb and Let-7 miRNA were the molecular targets of Lin28. Overexpression of Lin28 in breast cancer cells considerably induced p21 and Rb expression and inhibited Let-7 miRNA levels. Our results indicate that Lin28 expression might be one mechanism underlying paclitaxel resistance in breast cancer, and Lin28 could be a potential target for overcoming paclitaxel resistance in breast cancer. PMID:22808086

  12. Lin28 mediates paclitaxel resistance by modulating p21, Rb and Let-7a miRNA in breast cancer cells.

    PubMed

    Lv, Kezhen; Liu, Liqun; Wang, Linbo; Yu, Jiren; Liu, Xiaojiao; Cheng, Yongxia; Dong, Minjun; Teng, Rongyue; Wu, Linjiao; Fu, Peifen; Deng, Wuguo; Hu, Wenxian; Teng, Lisong

    2012-01-01

    Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemoresistance remained unknown. In this study, we investigated the association of Lin28 with paclitaxel resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines and tumor tissues. We found that the expression level of Lin28 was closely associated with the resistance to paclitaxel treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to paclitaxel than the MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which had low-level expression of Lin28. Knocking down of Lin28 in Lin28 high expression T47D cells increased the sensitivity to paclitaxel treatment, while stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to paclitaxel treatment, resulting in a significant increase of IC50 values of paclitaxel. Transfection with Lin28 also significantly inhibited paclitaxel-induced apoptosis. We also found that Lin28 expression was dramatically increased in tumor tissues after neoadjuvant chemotherapy or in local relapse or metastatic breast cancer tissues. Moreover, further studies showed that p21, Rb and Let-7 miRNA were the molecular targets of Lin28. Overexpression of Lin28 in breast cancer cells considerably induced p21 and Rb expression and inhibited Let-7 miRNA levels. Our results indicate that Lin28 expression might be one mechanism underlying paclitaxel resistance in breast cancer, and Lin28 could be a potential target for overcoming paclitaxel resistance in breast cancer.

  13. Extracellular Signal-regulated Kinases (ERKs) Phosphorylate Lin28a Protein to Modulate P19 Cell Proliferation and Differentiation.

    PubMed

    Liu, Xiangyuan; Chen, Min; Li, Long; Gong, Liyan; Zhou, Hu; Gao, Daming

    2017-03-10

    Lin28a, originally discovered in the nematode Caenorhabditis elegans and highly conserved across species, is a well characterized regulator of let-7 microRNA (miRNA) and is implicated in cell proliferation and pluripotency control. However, little is known about how Lin28a function is modulated at the post-translational level and thereby responds to major signaling pathways. Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. By editing lin28a gene with the CRISPR/Cas9-based method, we generated P19 mouse embryonic carcinoma stem cells expressing Lin28a-S200A (phospho-deficient) and Lin28a-S200D (phospho-mimetic) mutants, respectively, to study the functional impact of Ser-200 phosphorylation. Lin28a-S200D-expressing cells, but not Lin28a-S200A-expressing or control P19 embryonic carcinoma cells, displayed impaired inhibition of let-7 miRNA and resulted in decreased cyclin D1, whereas Lin28a-S200A knock-in cells expressed less let-7 miRNA, proliferated faster, and exhibited differentiation defect upon retinoic acid induction. Therefore our results support that ERK kinase-mediated Lin28a phosphorylation may be an important mechanism for pluripotent cells to facilitate the escape from the self-renewal cycle and start the differentiation process. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. The ubiquitin ligase human TRIM71 regulates let-7 microRNA biogenesis via modulation of Lin28B protein.

    PubMed

    Lee, Seo Hyun; Cho, Sungchan; Kim, M Sun; Choi, Kwangman; Cho, Jae Youl; Gwak, Ho-Shin; Kim, Youn-Jae; Yoo, Heon; Lee, Seung-Hoon; Park, Jong Bae; Kim, Jong Heon

    2014-05-01

    let-7 microRNA (miRNA) is implicated in various biological processes, and its downregulation essentially linked to human malignancy. Regulation of gene expression of the let-7 family is critically linked to RNA-binding proteins. For instance, Lin28B and its paralog, Lin28A, inhibit the pre-let-7 precursor from being processed to mature miRNA by recruiting terminal uridyltransferase, TUT4, which adds oligomeric U at the 3' end, suggesting that deregulation of Lin28B, together with Lin28A, may alter various biological processes through modulation of let-7 expression. Here, we showed that the Lin28B protein level is regulated via ubiquitin-mediated proteasomal degradation, and identified the ubiquitin ligase as human TRIM-NHL domain-containing TRIM71. In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination. Compared with its paralog, Lin28A, a C-terminal unique ~50 amino acid stretch of Lin28B is essential for TRIM71 interactions and subsequent polyubiquitination. Moreover, the N-terminal RING finger motif of TRIM71 is critical for protein-protein interactions and polyubiquitination of Lin28B, and consequent let-7 expression. Consistent with the let-7 stimulatory role of TRIM71 via Lin28B polyubiquitination, specific knockdown of TRIM71 led to downregulation of let-7 expression. Expression of one of the known let-7 targets, HMGA2, was derepressed after knockdown of TRIM71. We additionally showed that enhanced expression of let-7 is part of a feedback loop that targets TRIM71 3'UTR, which contains two conserved let-7 target sites. Our findings collectively reveal critical aspects of regulatory complexity of let-7 biogenesis at the posttranscriptional level. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Expression of exogenous LIN28 contributes to proliferation and survival of mouse primary cortical neurons in vitro.

    PubMed

    Bhuiyan, M I H; Lee, J-H; Kim, S Y; Cho, K-O

    2013-09-17

    LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. In this study, we investigated the effect of constitutively expressing exogenous LIN28 on neuronal cell proliferation and viability in vitro. Plasmids containing LIN28-green fluorescent protein (GFP) or GFP were introduced into the embryonic mouse brains at E14.5 by in utero electroporation. Two days after electroporation, embryonic cortices were harvested and cultured. It was found that transfected cells stably overexpressed LIN28 in vitro. Viability curve from live cell imaging showed that the number of GFP-expressing cells decreased over time in line with naive primary cortical neurons. In contrast, the number of LIN28-GFP-overexpressing neurons initially increased and remained high at later time-points in culture than GFP-expressing cells. Double immunofluorescence showed that at an early time in culture, the number of Ki-67/GFP double-positive cells was higher in the LIN28-GFP group than that of controls. Moreover, there were significantly lower numbers of condensed nuclei/GFP- and cleaved caspase-3/GFP-positive cells in the LIN28-GFP groups compared to control GFP. Furthermore, it was confirmed that the LIN28-GFP-expressing cells at days in vitro (DIV)13 were neuronal nuclei (NeuN)-positive mature neurons. Finally, the expression of insulin-like growth factor 2 (IGF-2) was induced in LIN28-expressing primary cortical neurons, which was not detected in controls. Taken together, our results indicate that the expression of exogenous LIN28 can promote the proliferation of neural progenitor cells and exert prosurvival effect on primary cortical neurons by inhibiting caspase-dependent apoptosis, possibly via upregulation of IGF-2. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated transcriptional repressor to a phosphorylated transcriptional activator.

    PubMed

    Leight, Elizabeth R; Murphy, John T; Fantz, Douglas A; Pepin, Danielle; Schneider, Daniel L; Ratliff, Thomas M; Mohammad, Duaa H; Herman, Michael A; Kornfeld, Kerry

    2015-03-01

    The LIN-1 ETS transcription factor plays a pivotal role in controlling cell fate decisions during development of the Caenorhabditis elegans vulva. Prior to activation of the RTK/Ras/ERK-signaling pathway, LIN-1 functions as a SUMOylated transcriptional repressor that inhibits vulval cell fate. Here we demonstrate using the yeast two-hybrid system that SUMOylation of LIN-1 mediates interactions with a protein predicted to be involved in transcriptional repression: the RAD-26 Mi-2β/CHD4 component of the nucleosome remodeling and histone deacetylation (NuRD) transcriptional repression complex. Genetic studies indicated that rad-26 functions to inhibit vulval cell fates in worms. Using the yeast two-hybrid system, we showed that the EGL-27/MTA1 component of the NuRD complex binds the carboxy-terminus of LIN-1 independently of LIN-1 SUMOylation. EGL-27 also binds UBC-9, an enzyme involved in SUMOylation, and MEP-1, a zinc-finger protein previously shown to bind LIN-1. Genetic studies indicate that egl-27 inhibits vulval cell fates in worms. These results suggest that LIN-1 recruits multiple proteins that repress transcription via both the SUMOylated amino-terminus and the unSUMOylated carboxy-terminus. Assays in cultured cells showed that the carboxy-terminus of LIN-1 was converted to a potent transcriptional activator in response to active ERK. We propose a model in which LIN-1 recruits multiple transcriptional repressors to inhibit the 1° vulval cell fate, and phosphorylation by ERK converts LIN-1 to a transcriptional activator that promotes the 1° vulval cell fate.

  17. EDITORIAL: Greetings from the new Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Bhattacharya, P.

    2004-04-01

    On 1 January, 2004, I assumed the position of Editor-in-Chief of Journal of Physics D: Applied Physics. I will start by saying that I will do my best to justify the confidence of the journal management and publishing staff in my abilities. I was fortunate to have been able to work, as an Editorial Board member, with my predecessor, the previous Editor-in-Chief, Professor Allister Ferguson. Allister has provided a high degree of intellectual stewardship for the journal in the last five years. He has made the job appear a worthy challenge for me. I therefore take this opportunity to thank Allister on behalf of the Editorial Board and publishing staff of the journal. Several other factors contributed to my decision to accept this position. The first is the group of people who actually go about the business of publishing. The Senior Publisher, Nicola Gulley (and her predecessor Sophy Le Masurier); the Managing Editor, Jill Membrey; the Publishing Administrators, Nina Blakesley and Sarah Towell; the Production Editor, Katie Gerrard and their office staff form an amazing group and have managed to make the operation of the journal incredibly efficient. An index of this is the speed with which incoming manuscripts are processed. The average time between the receipt of a manuscript and its web publication, if accepted, is 130 days. This is three to five times shorter than for most other journals. A factor that contributes to this success is a responsive pool of referees that the publishing staff have as a valuable resource. Ultimately, the standard bearers of any journal are the referees. Therefore, a grateful `thank you' is due from all of us at J. Phys. D to all our referees, who diligently perform this honourable task. The Associate Editors of the journal, Professors Lawler, Margaritondo and O'Grady, also provide immense scientific leadership. They help in defining new directions for the journal and in the publishing process. Last, but not least, a remarkable asset of

  18. Problems faced by editors of peer reviewed medical journals.

    PubMed

    Jawaid, Shaukat A

    2004-01-01

    Forty-six medical and dental journals are published from Pakistan of which only 29 are currently recognized by the Pakistan Medical and Dental Council. Only a few are peer reviewed. Six are indexed in Medline while EMBASE Excerpta Medica and World Health Organization Index Medicus for Eastern Mediterranean Region cover others. Editors of the peer reviewed medical journals are faced with numerous problems, which relate to the authors. Some of these are: shortage of quality of manuscripts, poor quality of reviewers, problems with indexation in international indexing services particularly Medline, duplicate submission and authorship and lastly, financial problems. Patronage from the Pharma industry is the major source of revenue which itself has serious implications. Editing a medical journal is a very stressful job and the editors have to work under too many pressures. A lot of useful data is presented at medical conferences, but a vast majority of it remains unpublished for various reasons, which adversely affects the citation rate from scientists from the developing third world countries in the world of medical literature. A few lectures on medical writing and research methodology to final year medical students will expose them to the art of medical writing. Specialty organizations can be persuaded to have a session on medical writing at their conferences, which will be extremely helpful not only to the potential new authors but also others, thereby improving the quality of their manuscripts. In addition to regular seminars, workshops for authors, reviewers and training courses for editors, subscribing to local medical journals by healthcare professionals and libraries are some of the measures that will help improve the situation to a great extent.

  19. EDITORIAL: Greetings from the new Editor-in-Chief Greetings from the new Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Nielsch, Kornelius

    2012-01-01

    On 1 January 2012 I will be assuming the position of Editor-in-Chief of the journal Semiconductor Science and Technology (SST). I am flattered by the confidence expressed in my ability to carry out this challenging job and I will try hard to justify this confidence. The previous Editor-in-Chief, Laurens Molenkamp, University of Würzburg, Germany, has worked tirelessly for the last ten years and has done an excellent job for the journal. Everyone at the journal is profoundly grateful for his leadership and for his achievements In 2012 several new members will join the Editorial Board: Professor Deli Wang (University of California, San Diego) with considerable expertise in semiconductor nanowires, Professor Saskia Fischer (Humboldt University, Berlin, Germany) with a background in semiconductor quantum devices, and Professor Erwin Kessels (Eindhoven University of Technology, Netherlands) with extensive experience in plasma processing of thin films and gate oxides. In particular, I want to express my gratitude to Professor Israel Bar-Joseph (Weizmann Institute of Science, Israel) and Professor Maria Tamargo (The City College of New York, USA), who will leave next year and who have vigorously served the Editorial Board for years. The journal has recently introduced a fast-track option for manuscripts. This option is a high-quality, high-profile outlet for new and important research across all areas of semiconductor research. Authors can expect to receive referee reports in less than 20 days from submission. Once accepted, you can expect the articles to be online within two or three weeks from acceptance and to be published in print in less than a month. Furthermore, all fast-track communications published in 2011 will be free to read for ten years. More detailed information on fast-track publication can be found on the following webpage: http://iopscience.iop.org/0268-1242/page/Fast track communications It is encouraging to see that since the journal introduced pre

  20. An Algebraic Specification Language and a Syntax Directed Editor.

    DTIC Science & Technology

    1984-12-01

    the various parts of specification produced by the language and describes an experimental syntax directed editor which uses the language’s grammar .. N...y t he ldngua ;ke aL>: describes an experimental syntax iirected eiitic w..icil~~s. the language’s grammar . 4 N 71 1ABLE OF CC4TENTS " i1TRODJCTION...zfinai _Lcif_;a.ioa. explandtion, of the neta-sym-hols useLd to ioco.cc teri-ia± * strings ir. the grammar are as fcliows: < > - A iname enclosed by

  1. Collective Text Editor: A New Interface Focused on Interaction Design

    NASA Astrophysics Data System (ADS)

    Behar, Patricia Alejandra; Macedo, Alexandra Lorandi; Passos, Jaire Ederson; Passos, Paula Caroline Schifino Jardim

    The Collective Text Editor ETC is a tool that follows Web 2.0 philosophy. Thus, its aim is to foster collaborative work mediated by computer and to create a space where the synchronous and asynchronous construction of collective texts among geographically dispersed users can be encouraged. The ETC is linked to a research project of NUTED/UFRGS. The present article deals with the reconstruction of the interface so as to adapt it to the current technological demands, giving it credibility and new personality.

  2. EDITORIAL: Greetings from the new Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Garcia, Ephrahim

    2008-02-01

    I am Professor Ephrahim Garcia, an Associate Professor at Sibley School of Mechanical and Aerospace Engineering at Cornell University in Ithaca, New York. I have been at Cornell University since 2002, spent four years as a Program Manager at the Defense Advanced Research Project Agency from 1998-2002, and before that seven years at the Department of Mechanical Engineering at Vanderbilt University in Nashville, Tennessee. I have served on the Editorial Advisory Board of Smart Materials and Structures (SMS) for the last six years. It is a humbling thing to be asked to take up the post of Editor-in-Chief in a field with so many talented researchers. I would like to say a heartfelt thanks to the members of the Editorial Board and IOP Publishing for their confidence in me. Most importantly, I would like to thank Professor Vijay Varadan of the University of Arkansas and Professor Richard Claus of Virginia Polytechnic Institute and State University for their efforts in launching the journal 16 years ago. They have been stewards, promoters and, especially Vijay, key to the operation and function of SMS for all these years, and our research community is indebted to them. Professors Varadan and Claus have dedicated their careers to the area of smart materials and structures and we are very grateful for their leadership, mentoring and contribution. SMS is a thriving journal offering papers on all technical areas concerned with smart materials, systems and structures from the micro- and nanoscale to the macroscale. The journal is undergoing some major changes, including the recent transferal of papers to IOP Publishing's peer-review management system. With this new system authors can expect fast publication times of around 4 or 5 months from submission, and excellent author service. In this world of ever changing technology, the Editorial Board and I aim to reduce the time to publication for researchers in this exciting area of science and engineering. I am in the process of

  3. JGR-Solid Earth and Planets editor Kenneth A. Hoffman

    NASA Astrophysics Data System (ADS)

    Enhancing the presence of geomagnetism and paleomagnetism in the Journal of Geophysical Research—Solid Earth and Planets is a principal goal for Ken Hoffman during his tenure as an editor of the journal. “Many researchers in paleomagnetism and rock magnetism tend to spread their publications among several journals,” Hoffman said, “perhaps having the mistaken impression that JGR may not always be the appropriate choice for their work.” Hoffman wants to alter this image of JGR, and he extends an open invitation for all significant contributions on topics in geomagnetism and paleomagnetism.

  4. LIN28A marks the spermatogonial progenitor population and regulates its cyclic expansion

    PubMed Central

    Chakraborty, P; Buaas, F.W.; Sharma, M; Snyder, E; de Rooij, D.G.; Braun, R.E.

    2014-01-01

    One of the hallmarks of highly proliferative adult tissues is the presence of a stem cell population that produces progenitor cells bound for differentiation. Progenitor cells undergo multiple transit amplifying (TA) divisions before initiating terminal differentiation. In the adult male germline, daughter cells arising from the spermatogonial stem cells (SSCs) undergo multiple rounds of TA divisions to produce undifferentiated clones of interconnected 2, 4, 8 and 16 cells, collectively termed Aundifferentiated (Aundiff) spermatogonia, before entering a stereotypic differentiation cascade. Although the number of TA divisions markedly affects the tissue output both at steady state and during regeneration, mechanisms regulating the expansion of the TA cell population are poorly understood in mammals. Here, we show that mice with a conditional deletion of Lin28a in the adult male germline, display impaired clonal expansion of the progenitor transit amplifying Aundiff spermatogonia. The in vivo proliferative activity of Aundiff spermatogonial cells as indicated by BrdU incorporation during S phase was reduced in the absence of LIN28A. Thus contrary to the role of LIN28A as a key determinant of cell fate signals in multiple stem cell lineages, in the adult male germline it functions as an intrinsic regulator of proliferation in the population of Aundiff TA spermatogonia. In addition, neither precocious differentiation nor diminished capacity for self-renewal potential as assessed by transplantation was observed, suggesting that neither LIN28A itself, nor the pool of Aal progenitor cells, substantially contribute to the functional stem cell compartment. PMID:24715688

  5. Lin28a regulates neuronal differentiation and controls miR-9 production

    PubMed Central

    Nowak, Jakub S.; Choudhury, Nila Roy; de Lima Alves, Flavia; Rappsilber, Juri; Michlewski, Gracjan

    2014-01-01

    microRNAs shape the identity and function of cells by regulating gene expression. It is known that brain-specific miR-9 is controlled transcriptionally; however, it is unknown whether post-transcriptional processes contribute to establishing its levels. Here, we show that miR-9 is regulated transcriptionally and post-transcriptionally during neuronal differentiation of the embryonic carcinoma cell line P19. We demonstrate that miR-9 is more efficiently processed in differentiated than undifferentiated cells. We reveal that Lin28a affects miR-9 by inducing the degradation of its precursor through a uridylation-independent mechanism. Furthermore, we show that constitutively expressed untagged but not GFP-tagged Lin28a decreases differentiation capacity of P19 cells, which coincides with reduced miR-9 levels. Finally, using an inducible system we demonstrate that Lin28a can also reduce miR-9 levels in differentiated P19 cells. Together, our results shed light on the role of Lin28a in neuronal differentiation and increase our understanding of the mechanisms regulating the level of brain-specific microRNAs. PMID:24722317

  6. LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation.

    PubMed

    Wang, Longfei; Nam, Yunsun; Lee, Anna K; Yu, Chunxiao; Roth, Kira; Chen, Casandra; Ransey, Elizabeth M; Sliz, Piotr

    2017-03-14

    LIN28 is an RNA binding protein that plays crucial roles in pluripotency, glucose metabolism, tissue regeneration, and tumorigenesis. LIN28 binds to the let-7 primary and precursor microRNAs through bipartite recognition and induces degradation of let-7 precursors (pre-let-7) by promoting oligouridylation by terminal uridylyltransferases (TUTases). Here, we report that the zinc knuckle domain (ZKD) of mouse LIN28 recruits TUT4 to initiate the oligouridylation of let-7 precursors. Our crystal structure of human LIN28 in complex with a fragment of pre-let-7f-1 determined to 2.0 Å resolution shows that the interaction between ZKD and RNA is constrained to a small cavity with a high druggability score. We demonstrate that the specific interaction between ZKD and pre-let-7 is necessary and sufficient to induce oligouridylation by recruiting the N-terminal fragment of TUT4 (NTUT4) and the formation of a stable ZKD:NTUT4:pre-let-7 ternary complex is crucial for the acquired processivity of TUT4. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Lin28a regulates neuronal differentiation and controls miR-9 production.

    PubMed

    Nowak, Jakub S; Choudhury, Nila Roy; de Lima Alves, Flavia; Rappsilber, Juri; Michlewski, Gracjan

    2014-04-11

    microRNAs shape the identity and function of cells by regulating gene expression. It is known that brain-specific miR-9 is controlled transcriptionally; however, it is unknown whether post-transcriptional processes contribute to establishing its levels. Here we show that miR-9 is regulated transcriptionally and post-transcriptionally during neuronal differentiation of the embryonic carcinoma cell line P19. We demonstrate that miR-9 is more efficiently processed in differentiated than in undifferentiated cells. We reveal that Lin28a affects miR-9 by inducing the degradation of its precursor through a uridylation-independent mechanism. Furthermore, we show that constitutively expressed untagged but not GFP-tagged Lin28a decreases differentiation capacity of P19 cells, which coincides with reduced miR-9 levels. Finally, using an inducible system we demonstrate that Lin28a can also reduce miR-9 levels in differentiated P19 cells. Together, our results shed light on the role of Lin28a in neuronal differentiation and increase our understanding of the mechanisms regulating the level of brain-specific microRNAs.

  8. Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment

    PubMed Central

    Ma, Wei; Ma, Jing; Xu, Jie; Qiao, Chong; Branscum, Adam; Cardenas, Andres; Baron, Andre T.; Schwartz, Peter; Maihle, Nita J.; Huang, Yingqun

    2013-01-01

    Emerging evidence suggests that the tumor microenvironment plays a critical role in regulating cancer stem cells (CSCs) and tumor progression through both autocrine and paracrine signaling. Elevated production of bone morphogenetic proteins (BMPs) from human ovarian cancer cells and stroma has been shown to increase CSC proliferation and tumor growth. Here, we report that Lin28, a stem cell factor, binds to BMP4 mRNA in epithelial ovarian carcinoma cells, thereby promoting BMP4 expression at the post-transcriptional level. As co-expression of Lin28 and Oct4 (another stem cell factor) has been implicated in ovarian cancer CSCs, we also determined that high levels of Lin28 are associated with an unfavorable prognosis when co-expressed with high levels of Oct4. Together, these findings uncover a new level of regulation of BMP4 expression and imply a novel Lin28/Oct4/BMP4-mediated mechanism of regulating ovarian tumor cell growth, thus holding potential for the development of new strategies for the diagnosis and treatment of ovarian cancer. PMID:23255092

  9. The Value of SCMC in SLA: Comments on Lin, Huang & Liou (2013)

    ERIC Educational Resources Information Center

    Taylor, Alan M.

    2014-01-01

    Meta-analytic methods are often used to determine the effectiveness of certain treatments across studies. However, we are often unaware of how a meta-analysis can provide value to researchers and practitioners. This paper offers a brief commentary on a meta-analysis conducted by Lin, Huang and Liou (2013) in LLT, providing further statistical…

  10. LinAir: A multi-element discrete vortex Weissinger aerodynamic prediction method

    NASA Technical Reports Server (NTRS)

    Durston, Donald A.

    1993-01-01

    LinAir is a vortex lattice aerodynamic prediction method similar to Weissinger's extended lifting-line theory, except that the circulation around a wing is represented by discrete horseshoe vortices, not a continuous distribution of vorticity. The program calculates subsonic longitudinal and lateral/directional aerodynamic forces and moments for arbitrary aircraft geometries. It was originally written by Dr. Ilan Kroo of Stanford University, and subsequently modified by the author to simplify modeling of complex configurations. The Polhamus leading-edge suction analogy was added by the author to extend the range of applicability of LinAir to low aspect ratio (i.e., fighter-type) configurations. A brief discussion of the theory of LinAir is presented, and details on how to run the program are given along with some comparisons with experimental data to validate the code. Example input and output files are given in the appendices to aid in understanding the program and its use. This version of LinAir runs in the VAX/VMS, Cray UNICOS, and Silicon Graphics Iris workstation environments at the time of this writing.

  11. The Value of SCMC in SLA: Comments on Lin, Huang & Liou (2013)

    ERIC Educational Resources Information Center

    Taylor, Alan M.

    2014-01-01

    Meta-analytic methods are often used to determine the effectiveness of certain treatments across studies. However, we are often unaware of how a meta-analysis can provide value to researchers and practitioners. This paper offers a brief commentary on a meta-analysis conducted by Lin, Huang and Liou (2013) in LLT, providing further statistical…

  12. Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a.

    PubMed

    Zhou, Yan; Li, Yue-Sheng; Bandi, Srinivasa Rao; Tang, Lingjuan; Shinton, Susan A; Hayakawa, Kyoko; Hardy, Richard R

    2015-04-06

    Mouse B cell precursors from fetal liver and adult bone marrow (BM) generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal "B-1" and adult "B-2." Recently, Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of B cell antigen receptor (BCR) signaling in this process was addressed. Here, we report key advances in our understanding of the regulation of B-1/B-2 development. First, modulation of Let-7 in fetal pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for the generation of B1a B cells from Lin28b-transduced BM progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertoire of Lin28b-induced BM B1a B cells differs from that of normal B1a, suggesting persisting differences from fetal progenitors. Finally, we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult pro-B cells and whose silencing by knockdown blocks B-1 development in fetal pro-B cells.

  13. The Lin28/let-7 axis is critical for myelination in the peripheral nervous system

    PubMed Central

    Gökbuget, Deniz; Pereira, Jorge A.; Bachofner, Sven; Marchais, Antonin; Ciaudo, Constance; Stoffel, Markus; Schulte, Johannes H.; Suter, Ueli

    2015-01-01

    MicroRNAs (miRNAs) are crucial regulators of myelination in the peripheral nervous system (PNS). However, the miRNAs species involved and the underlying mechanisms are largely unknown. We found that let-7 miRNAs are highly abundant during PNS myelination and that their levels are inversely correlated to the expression of lin28 homolog B (Lin28B), an antagonist of let-7 accumulation. Sustained expression of Lin28B and consequently reduced levels of let-7 miRNAs results in a failure of Schwann cell myelination in transgenic mouse models and in cell culture. Subsequent analyses revealed that let-7 miRNAs promote expression of the myelination-driving master transcription factor Krox20 (also known as Egr2) through suppression of myelination inhibitory Notch signalling. We conclude that the Lin28B/let-7 axis acts as a critical driver of PNS myelination, in particular by regulating myelination onset, identifying this pathway also as a potential therapeutic target in demyelinating diseases. PMID:26466203

  14. Mip/LIN-9 can inhibit cell proliferation independent of the pocket proteins.

    PubMed

    Pilkinton, Mark; Sandoval, Raudel; Barrett, Kelly; Tian, Xinyong; Colamonici, Oscar R

    2007-01-01

    Progression through the G1-phase of the cell cycle requires that cyclin D and CDK4 phosphorylate pRB and the other pocket proteins, p107 and p130. Cyclin E and CDK2 further phosphorylate pRB to complete its inactivation and allow the cell to enter S-phase. These phosphorylation events lead to the inactivation of the antiproliferative effect of the pocket proteins. The pocket proteins are the main targets of CDK4, and its unregulated activity can contribute to carcinogenesis. Mip/LIN9 is a recently described protein with growth suppressor, as well as growth promoting effects due to its ability to stabilize B-Myb and induce genes required for S phase and mitosis. The finding that a mutation that deletes the first 84 amino acids of Mip/LIN-9 corrects the defects of the CDK4 knockout mouse suggests that it should have a growth repressor effect that is blocked by CDK4. However, overexpression of cyclin D only partially blocks the inhibitory effect of Mip/LIN-9 on cell proliferation. Here, we performed experiments to further understand the antiproliferative effect of Mip/LIN-9 within the context of the pocket proteins. Our results suggest that there is a pocket protein-independent mechanism of the Mip/LIN-9 antiproliferative effect since it can be observed in cells with ablation of the three members of the family, and in NIH3T3 cells expressing the adenovirus E1A-12S protein. Altogether, the independence from the pocket proteins and the partial blockade of the antiproliferative effect produced by expression of cyclin D suggest that the role of Mip/LIN-9 downstream of CDK4 may be more closely related to the activation of B-Myb and the induction of S/M genes. Importantly, the regulatory effect of CDK4 is not due to direct phosphorylation of Mip/LIN-9 by this kinase or even CDK2, suggesting an indirect mechanism such as phosphorylation of the pocket proteins.

  15. Polyamines are oncometabolites that regulate the LIN28/let-7 pathway in colorectal cancer cells.

    PubMed

    Paz, Edwin A; LaFleur, Bonnie; Gerner, Eugene W

    2014-02-01

    Polyamine metabolism is a highly coordinated process that is essential for normal development and neoplastic growth in mammals. Although polyamine metabolism is a validated pathway for prevention of carcinogenesis, the mechanisms by which polyamines elicit their tumorigenic effects are poorly understood. In this study, we investigated the role of polyamine metabolism in colon cancer by screening a non-coding RNA (ncRNA) platform to identify polyamine responsive signaling nodes. We report that multiple non-coding RNAs are altered by polyamine depletion including induction of microRNA (miRNA) let-7i, a member of the tumor suppressive let-7 family. The let-7 family targets several RNAs for translational repression, including the growth-associated transcription factor HMGA2 and is negatively regulated by the pluripotency factor LIN28. Depletion of polyamines using difluoromethylornithine (DFMO) or genetic knockdown of the polyamine-modified eukaryotic translation initiation factor 5A isoforms 1 and 2 (eIF5A1/2) resulted in robust reduction of both HMGA2 and LIN28. Locked nucleic acid (LNA) oligonucleotides targeting the seed region of the let-7 family rescued the expression of HMGA2, but not LIN28, in both DFMO-treated and eIF5A1/2 knockdown cultures. Our findings suggest that polyamines are oncometabolites that influence specific aspects of tumorigenesis by regulating pluripotency associated factors, such as LIN28, via an eIF5A-dependent but let-7-independent mechanism while the expression of proliferation-related genes regulated by let-7, such as HMGA2, is mediated through microRNA mediated repression. Therefore, manipulating polyamine metabolism may be a novel method of targeting the LIN28/let-7 pathway in specific disease states. © 2013 Wiley Periodicals, Inc.

  16. Aire promotes the self-renewal of embryonic stem cells through Lin28.

    PubMed

    Bin, Gu; Jiarong, Zhang; Shihao, Wang; Xiuli, Song; Cheng, Xu; Liangbiao, Chen; Ming, Zhang

    2012-10-10

    Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire on ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes, and cleavage-stage embryos, and the expression level of Lin28 is correlated with the expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of ES cells through a specific pathway (i.e., the activation of Lin28 and the inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms behind the establishment and sustenance of pluripotent identity.

  17. Aire Promotes the Self-Renewal of Embryonic Stem Cells Through Lin28

    PubMed Central

    Bin, Gu; Jiarong, Zhang; Shihao, Wang; Xiuli, Song; Cheng, Xu

    2012-01-01

    Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire on ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes, and cleavage-stage embryos, and the expression level of Lin28 is correlated with the expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of ES cells through a specific pathway (i.e., the activation of Lin28 and the inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms behind the establishment and sustenance of pluripotent identity. PMID:22540148

  18. Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer*

    PubMed Central

    Li, Ning; Zhong, Xiaomin; Lin, Xiaojuan; Guo, Jinyi; Zou, Lian; Tanyi, Janos L.; Shao, Zhongjun; Liang, Shun; Wang, Li-Ping; Hwang, Wei-Ting; Katsaros, Dionyssios; Montone, Kathleen; Zhao, Xia; Zhang, Lin

    2012-01-01

    The RNA-binding protein LIN28A regulates the translation and stability of a large number of mRNAs as well as the biogenesis of certain miRNAs in embryonic stem cells and developing tissues. Increasing evidence indicates that LIN28A functions as an oncogene promoting cancer cell growth. However, little is known about its molecular mechanism of cell cycle regulation in cancer. Using tissue microarrays, we found that strong LIN28A expression was reactivated in about 10% (7.1–17.1%) of epithelial tumors (six tumor types, n = 369). Both in vitro and in vivo experiments demonstrate that LIN28A promotes cell cycle progression in cancer cells. Genome-wide RNA-IP-chip experiments indicate that LIN28A binds to thousands of mRNAs, including a large group of cell cycle regulatory mRNAs in cancer and embryonic stem cells. Furthermore, the ability of LIN28A to stimulate translation of LIN28A-binding mRNAs, such as CDK2, was validated in vitro and in vivo. Finally, using a combined gene expression microarray and bioinformatics approach, we found that LIN28A also regulates CCND1 and CDC25A expression and that this is mediated by inhibiting the biogenesis of let-7 miRNA. Taken together, these results demonstrate that LIN28A is reactivated in about 10% of epithelial tumors and promotes cell cycle progression by regulation of both mRNA translation (let-7-independent) and miRNA biogenesis (let-7-dependent). PMID:22467868

  19. Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer.

    PubMed

    Li, Ning; Zhong, Xiaomin; Lin, Xiaojuan; Guo, Jinyi; Zou, Lian; Tanyi, Janos L; Shao, Zhongjun; Liang, Shun; Wang, Li-Ping; Hwang, Wei-Ting; Katsaros, Dionyssios; Montone, Kathleen; Zhao, Xia; Zhang, Lin

    2012-05-18

    The RNA-binding protein LIN28A regulates the translation and stability of a large number of mRNAs as well as the biogenesis of certain miRNAs in embryonic stem cells and developing tissues. Increasing evidence indicates that LIN28A functions as an oncogene promoting cancer cell growth. However, little is known about its molecular mechanism of cell cycle regulation in cancer. Using tissue microarrays, we found that strong LIN28A expression was reactivated in about 10% (7.1-17.1%) of epithelial tumors (six tumor types, n = 369). Both in vitro and in vivo experiments demonstrate that LIN28A promotes cell cycle progression in cancer cells. Genome-wide RNA-IP-chip experiments indicate that LIN28A binds to thousands of mRNAs, including a large group of cell cycle regulatory mRNAs in cancer and embryonic stem cells. Furthermore, the ability of LIN28A to stimulate translation of LIN28A-binding mRNAs, such as CDK2, was validated in vitro and in vivo. Finally, using a combined gene expression microarray and bioinformatics approach, we found that LIN28A also regulates CCND1 and CDC25A expression and that this is mediated by inhibiting the biogenesis of let-7 miRNA. Taken together, these results demonstrate that LIN28A is reactivated in about 10% of epithelial tumors and promotes cell cycle progression by regulation of both mRNA translation (let-7-independent) and miRNA biogenesis (let-7-dependent).

  20. Editorial independence at medical journals owned by professional associations: a survey of editors.

    PubMed

    Davis, Ronald M; Müllner, Marcus

    2002-10-01

    The purpose of this study was to assess the degree of editorial independence at a sample of medical journals and the relationship between the journals and their owners. We surveyed the editors of 33 medical journals owned by not-for-profit organizations ("associations"), including 10 journals represented on the International Committee of Medical Journal Editors (nine of which are general medical journals) and a random sample of 23 specialist journals with high impact factors that are indexed by the Institute for Scientific Information. The main outcome measures were the authority to hire, fire, and oversee the work of the editor; the editor's tenure and financial compensation; control of the journal's budget; publication of material about the association; and the editor's perceptions about editorial independence and pressure over editorial content. Of the 33 editors, 23 (70%) reported having complete editorial freedom, and the remainder reported a high level of freedom (a score of > or = 8, where 10 equals complete editorial freedom and 1 equals no editorial freedom). Nevertheless, a substantial minority of editors reported having received at least some pressure in recent years over editorial content from the association's leadership (42%), senior staff (30%), or rank-and-file members (39%). The association's board of directors has the authority to hire (48%) or fire (55%) the editor for about half of the journals, and the editor reports to the board for 10 journals (30%). Twenty-three editors (70%) are appointed for a specific term (median term = 5 years). Three-fifths of the journals have no control over their profit, and the majority of journals use the association's legal counsel and/or media relations staff. Stronger safeguards are needed to give editors protection against pressure over editorial content, including written guarantees of editorial freedom and governance structures that support those guarantees. Strong safeguards are also needed because editors

  1. 29 CFR 793.8 - “News editor.”

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

  2. 29 CFR 793.8 - “News editor.”

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

  3. 29 CFR 793.8 - “News editor.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

  4. 29 CFR 793.8 - “News editor.”

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

  5. 29 CFR 793.8 - “News editor.”

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

  6. Gene targeting, genome editing: from Dolly to editors.

    PubMed

    Tan, Wenfang; Proudfoot, Chris; Lillico, Simon G; Whitelaw, C Bruce A

    2016-06-01

    One of the most powerful strategies to investigate biology we have as scientists, is the ability to transfer genetic material in a controlled and deliberate manner between organisms. When applied to livestock, applications worthy of commercial venture can be devised. Although initial methods used to generate transgenic livestock resulted in random transgene insertion, the development of SCNT technology enabled homologous recombination gene targeting strategies to be used in livestock. Much has been accomplished using this approach. However, now we have the ability to change a specific base in the genome without leaving any other DNA mark, with no need for a transgene. With the advent of the genome editors this is now possible and like other significant technological leaps, the result is an even greater diversity of possible applications. Indeed, in merely 5 years, these 'molecular scissors' have enabled the production of more than 300 differently edited pigs, cattle, sheep and goats. The advent of genome editors has brought genetic engineering of livestock to a position where industry, the public and politicians are all eager to see real use of genetically engineered livestock to address societal needs. Since the first transgenic livestock reported just over three decades ago the field of livestock biotechnology has come a long way-but the most exciting period is just starting.

  7. An editor for the generation and customization of geometry restraints

    DOE PAGES

    Moriarty, Nigel W.; Draizen, Eli J.; Adams, Paul D.

    2017-02-01

    Chemical restraints for use in macromolecular structure refinement are produced by a variety of methods, including a number of programs that use chemical information to generate the required bond, angle, dihedral, chiral and planar restraints. These programs help to automate the process and therefore minimize the errors that could otherwise occur if it were performed manually. Furthermore, restraint-dictionary generation programs can incorporate chemical and other prior knowledge to provide reasonable choices of types and values. However, the use of restraints to define the geometry of a molecule is an approximation introduced with efficiency in mind. The representation of a bondmore » as a parabolic function is a convenience and does not reflect the true variability in even the simplest of molecules. Another complicating factor is the interplay of the molecule with other parts of the macromolecular model. Finally, difficult situations arise from molecules with rare or unusual moieties that may not have their conformational space fully explored. These factors give rise to the need for an interactive editor for WYSIWYG interactions with the restraints and molecule. Restraints Editor, Especially Ligands (REEL) is a graphical user interface for simple and error-free editing along with additional features to provide greater control of the restraint dictionaries in macromolecular refinement.« less

  8. Making a height field editor for WireMan

    SciTech Connect

    Cano, J.

    1994-04-01

    The focus of this project is to modify and write new code for a program named WireMan. WireMan draws in 3-D using items from a menu (cones, spheres, etc.). One of the items which can be selected is called the height field. The height field, as it currently appears in WireMan, is a 3-D graph of a set equation. Originally, the height field was supposed to be able to display any curve the user may need. However, because of lack of time and programmers, the height field was never completed and has remained at this constant curve since its creation. To change it a user needs to modify progra mcode, thus, a height field editor is necessary. Through the editor, the user will be able to modify the height field by either equation of matrix. The latter will allow the user to determine a curve for the height field according to matrix or grid entries (of the form n x n, where up to 10 x 10 entries can be made). The grid will then be stretched and evaluated over the height field plane (which consists of 512-512 generated entries) and the curve will then be generated. The difficulties and the results of the project are outlined according to their occurrences throughout the paper.

  9. An editor for the generation and customization of geometry restraints

    PubMed Central

    Moriarty, Nigel W.; Adams, Paul D.

    2017-01-01

    Chemical restraints for use in macromolecular structure refinement are produced by a variety of methods, including a number of programs that use chemical information to generate the required bond, angle, dihedral, chiral and planar restraints. These programs help to automate the process and therefore minimize the errors that could otherwise occur if it were performed manually. Furthermore, restraint-dictionary generation programs can incorporate chemical and other prior knowledge to provide reasonable choices of types and values. However, the use of restraints to define the geometry of a molecule is an approximation introduced with efficiency in mind. The representation of a bond as a parabolic function is a convenience and does not reflect the true variability in even the simplest of molecules. Another complicating factor is the interplay of the molecule with other parts of the macromolecular model. Finally, difficult situations arise from molecules with rare or unusual moieties that may not have their conformational space fully explored. These factors give rise to the need for an interactive editor for WYSIWYG interactions with the restraints and molecule. Restraints Editor, Especially Ligands (REEL) is a graphical user interface for simple and error-free editing along with additional features to provide greater control of the restraint dictionaries in macromolecular refinement. PMID:28177308

  10. A Generic Metadata Editor Supporting System Using Drupal CMS

    NASA Astrophysics Data System (ADS)

    Pan, J.; Banks, N. G.; Leggott, M.

    2011-12-01

    Metadata handling is a key factor in preserving and reusing scientific data. In recent years, standardized structural metadata has become widely used in Geoscience communities. However, there exist many different standards in Geosciences, such as the current version of the Federal Geographic Data Committee's Content Standard for Digital Geospatial Metadata (FGDC CSDGM), the Ecological Markup Language (EML), the Geography Markup Language (GML), and the emerging ISO 19115 and related standards. In addition, there are many different subsets within the Geoscience subdomain such as the Biological Profile of the FGDC (CSDGM), or for geopolitical regions, such as the European Profile or the North American Profile in the ISO standards. It is therefore desirable to have a software foundation to support metadata creation and editing for multiple standards and profiles, without re-inventing the wheels. We have developed a software module as a generic, flexible software system to do just that: to facilitate the support for multiple metadata standards and profiles. The software consists of a set of modules for the Drupal Content Management System (CMS), with minimal inter-dependencies to other Drupal modules. There are two steps in using the system's metadata functions. First, an administrator can use the system to design a user form, based on an XML schema and its instances. The form definition is named and stored in the Drupal database as a XML blob content. Second, users in an editor role can then use the persisted XML definition to render an actual metadata entry form, for creating or editing a metadata record. Behind the scenes, the form definition XML is transformed into a PHP array, which is then rendered via Drupal Form API. When the form is submitted the posted values are used to modify a metadata record. Drupal hooks can be used to perform custom processing on metadata record before and after submission. It is trivial to store the metadata record as an actual XML file

  11. Lin28/let-7/Bcl-xL pathway: the underlying mechanism of drug resistance in Hep3B cells.

    PubMed

    Tian, Nan; Han, Ziwu; Li, Zhaohui; Zhou, Mingjie; Fan, Chunlei

    2014-09-01

    Hepatocellular carcinoma (HCC) is highly resistant to chemotherapeutic drugs, which markedly reduces the effect of chemotherapy. Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemotherapy drug resistance is unknown. In the present study, we established a drug-resistant Hep3B cell line to investigate the association between Lin28 and drug resistance in HCC, and we identified the underlying mechanisms. We found that the expression of Lin28 was closely associated with resistance to paclitaxel. The drug‑resistant Hep3B cell line, which expresses high levels of Lin28, is more resistant to paclitaxel and other anticancer drugs than the parental cell line. Moreover, further studies showed that dysregulation of Lin28 inhibited let-7 family microRNA levels and upregulated the anti-apoptotic protein Bcl-xL, which is a target of let-7. Our results indicate that the Lin28/let-7/Bcl-xL pathway underlies the drug resistance of Hep3B cells.

  12. Does Lin28 Antagonize miRNA-Mediated Repression by Displacing miRISC from Target mRNAs?

    PubMed

    Kallen, Amanda N; Ma, Jing; Huang, Yingqun

    2012-01-01

    Lin28 is a developmentally regulated RNA-binding protein that plays important roles in diverse physiological and pathological processes including oncogenesis and brain synaptic function. These pleiotropic roles of Lin28 are mechanistically linked both to its ability to directly stimulate translation of genes involved primarily in cell growth and metabolism and to its ability to block biogenesis of a subset of miRNAs including the let-7 family of miRNAs. In the case of direct stimulation of gene expression, Lin28 binds to targeted mRNAs through recognition of Lin28-responsive elements (LREs) within mRNAs and recruits RNA helicase A (RHA) to promote translation. RHA belongs to the DEAD-box protein family of RNA helicases, which generally catalyze ATP-dependent unwinding of RNA duplexes or remodeling of ribonucleoprotein complexes (RNPs). Since any given mRNA can potentially be inhibited by miRNAs bearing complementary sequences, we hypothesize that binding of Lin28 to LREs not only nucleates the binding of multiple Lin28 molecules to the same mRNA, but also leads to remodeling of RNPs through recruitment of RHA and causes release of inhibitory miRNA-induced silencing complexes bound to the mRNA. This mode of action may contribute to Lin28-mediated stimulation of translation in both tumor and neuronal cells.

  13. LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency.

    PubMed

    Tsanov, Kaloyan M; Pearson, Daniel S; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T; Powers, John T; Osborne, Jihan K; Kane, Susan; Gygi, Steven P; Gregory, Richard I; Daley, George Q

    2017-01-01

    Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced the effect of LIN28 on its direct mRNA targets, revealing a mechanism that uncouples LIN28's let-7-dependent and -independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naive to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signalling, post-transcriptional gene control, and cell fate regulation.

  14. Identification of small molecule inhibitors of the Lin28-mediated blockage of pre-let-7g processing.

    PubMed

    Lightfoot, Helen L; Miska, Eric A; Balasubramanian, Shankar

    2016-11-02

    The protein Lin28 and microRNA let-7 play critical roles in mammalian development and human disease. Lin28 inhibits let-7 biogenesis through direct interaction with let-7 precursors (pre-let-7). Accumulating evidence in vitro and in vivo suggests this interaction plays a dominant role in embryonic stem cell self-renewal and tumorigenesis. Thus the Lin28-let-7 interaction might be an attractive drug target, if not for the well-known difficulties in targeting protein-RNA interactions with drugs. The identification and development of suitable probe molecules to further elucidate therapeutic potential, as well as mechanistic details of this pathway will be valuable. We report the development and application of a biophysical high-throughput screening assay for the identification of small molecule inhibitors of the Lin28-pre-let-7 interaction. A library of pharmacologically active small molecules was screened and several small molecule inhibitors were identified and biochemically validated. Of these four validated inhibitors, two compounds successfully restored processing of pre-let-7g in the presence of Lin28, validating the concept. Thus, we have identified examples of small molecule inhibitors of the interaction between Lin28 and pre-let-7. This study provides a proof of concept for small molecule inhibitors that antagonise the effects of Lin28 and enhance processing of let-7 miRNA.

  15. Biodegradation of γ-hexachlorocyclohexane by transgenic hairy root cultures of Cucurbita moschata that accumulate recombinant bacterial LinA.

    PubMed

    Nanasato, Yoshihiko; Namiki, Sayuri; Oshima, Masao; Moriuchi, Ryota; Konagaya, Ken-Ichi; Seike, Nobuyasu; Otani, Takashi; Nagata, Yuji; Tsuda, Masataka; Tabei, Yutaka

    2016-09-01

    γ-HCH was successfully degraded using LinA-expressed transgenic hairy root cultures of Cucurbita moschata . Fusing an endoplasmic reticulum-targeting signal peptide to LinA was essential for stable accumulation in the hairy roots. The pesticide γ-hexachlorocyclohexane (γ-HCH) is a persistent organic pollutant (POP) that raises public health and environmental pollution concerns worldwide. Although several isolates of γ-HCH-degrading bacteria are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the bacterial survival rate. Cucurbita species incorporate significant amounts of POPs from soils compared with other plant species. Here, we describe a novel bioremediation strategy that combines the bacterial degradation of γ-HCH and the efficient uptake of γ-HCH by Cucurbita species. We produced transgenic hairy root cultures of Cucurbita moschata that expressed recombinant bacterial linA, isolated from the bacterium Sphingobium japonicum UT26. The LinA protein was accumulated stably in the hairy root cultures by fusing an endoplasmic reticulum (ER)-targeting signal peptide to LinA. Then, we demonstrated that the cultures degraded more than 90 % of γ-HCH (1 ppm) overnight and produced the γ-HCH metabolite 1,2,4-trichlorobenzene, indicating that LinA degraded γ-HCH. These results indicate that the gene linA has high potential for phytoremediation of environmental γ-HCH.

  16. Dynamic localization of LIN-5 and GPR-1/2 to cortical force generation domains during spindle positioning

    PubMed Central

    Park, Dae Hwi; Rose, Lesilee S.

    2008-01-01

    G protein signaling pathways regulate mitotic spindle positioning during cell division in many systems. In C. elegans embryos, Gα subunits act with the positive regulators GPR-1/2 and LIN-5 to generate cortical pulling forces for posterior spindle displacement during the first asymmetric division. GPR-1/2 are asymmetrically localized at the posterior cortex by PAR polarity cues at this time. Here we show that LIN-5 colocalizes with GPR-1/2 in one-cell embryos during spindle displacement. Significantly, we also find that LIN-5 and GPR-1/2 are localized to the opposite, anterior cortex in a polarity dependent manner during the nuclear centration and rotation movements that orient the forming spindle onto the polarity axis. The depletion of LIN-5 or GPR-1/2 results in decreased centration and rotation rates, indicating a role in force generation at this stage. The localization of LIN- 5 and GPR-1/2 is largely interdependent and requires Gα. Further, LIN-5 immunoprecipitates with Gα in vivo, and association is GPR-1/2 dependent. These results suggest that a complex of Gα /GPR- 1/2/LIN-5 is asymmetrically localized in response to polarity cues, and this may be the active signaling complex that transmits asymmetries to the force generation machinery during both nuclear rotation and spindle displacement. PMID:18234174

  17. Science journal editors' views on publication ethics: results of an international survey.

    PubMed

    Wager, E; Fiack, S; Graf, C; Robinson, A; Rowlands, I

    2009-06-01

    Breaches of publication ethics such as plagiarism, data fabrication and redundant publication are recognised as forms of research misconduct that can undermine the scientific literature. We surveyed journal editors to determine their views about a range of publication ethics issues. Questionnaire sent to 524 editors-in-chief of Wiley-Blackwell science journals asking about the severity and frequency of 16 ethical issues at their journals, their confidence in handling such issues, and their awareness and use of guidelines. Responses were obtained from 231 editors (44%), of whom 48% edited healthcare journals. The general level of concern about the 16 issues was low, with mean severity scores of <1 (on a scale of 0-3) for all but one. The issue of greatest concern (mean score 1.19) was redundant publication. Most editors felt confident in handling the issues, with <15% feeling "not at all confident" for all but one of the issues (gift authorship, 22% not confident). Most editors believed such problems occurred less than once a year and >20% of the editors stated that 12 of the 16 items never occurred at their journal. However, 13%-47% did not know the frequency of the problems. Awareness and use of guidelines was generally low. Most editors were unaware of all except other journals' instructions. Most editors of science journals seem not very concerned about publication ethics and believe that misconduct occurs only rarely in their journals. Many editors are unfamiliar with available guidelines but would welcome more guidance or training.

  18. Lin28 regulates the expression of neuropeptide Y receptors and oocyte-specific homeobox genes in mouse embryonic stem cells.

    PubMed

    Park, Geon Tae; Seo, You-Mi; Lee, Su-Yeon; Lee, Kyung-Ah

    2012-06-01

    Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.

  19. LIN28: a regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer.

    PubMed

    Sakurai, Minako; Miki, Yasuhiro; Masuda, Mariko; Hata, Shuko; Shibahara, Yukiko; Hirakawa, Hisashi; Suzuki, Takashi; Sasano, Hironobu

    2012-09-01

    A tumor-suppressor gene, let-7 microRNA (miRNA) family, is often inactivated in various human malignancies. LIN28 is a RNA-binding protein that has been well characterized for regulation of let-7 maturation in undifferentiated embryonic stem cells at post-transcriptional level. Oncogenic regulation of let-7 miRNAs has been demonstrated in several human malignancies but their correlation with LIN28 has not been studied in breast cancer. We therefore explored a possible mechanism of tumorigenesis in breast carcinoma tissue via an alternation of let-7 miRNA precursor processing by LIN28 in this study. A total of 26 breast cancer surgical pathology specimens were evaluated for LIN28 and LIN28B expression using immunohistochemistry. We then isolated carcinoma cells in 21 cases using laser capture microdissection, and the miRNAs from these samples were profiled using PCR array analysis. LIN28 status was positively correlated with ERα, PR, and Ki-67 status and inversely correlated with HER2 status. These results suggest the possible involvement of LIN28 in regulation of sex steroid dependent cell proliferation of breast carcinoma cells. We further demonstrated that expression of let-7a, let-7c, let-7d (P=0.026) and let-7f (P=0.016) were inversely correlated with those of LIN28. These results also suggest that LIN28 promotes tumorigenic activity by suppressing let-7 miRNA maturation in breast carcinoma cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Intron-specific patterns of divergence of lin-11 regulatory function in the C. elegans nervous system.

    PubMed

    Amon, Siavash; Gupta, Bhagwati P

    2017-04-01

    The diversity of neurons in the nervous system is specified by many genes, including those that encode transcription factors (TFs) and play crucial roles in coordinating gene transcription. To understand how the spatiotemporal expression of TF genes is regulated to generate neuronal diversity, we used one member of the LIM-Hox family, lin-11, as a model that is necessary for the differentiation of amphid neurons in the nematode C. elegans and a related species C. briggsae. We characterized transcriptional regulation of lin-11 and uncovered regulatory roles of two of the largest introns, intron 3 and intron 7. These introns promote lin-11 expression in non-overlapping sets of neurons. Phenotypic rescue experiments in C. elegans revealed that intron 3 is capable of restoring lin-11 function based on gene expression patterns and behavioral assays. Interestingly, intron 3-driven reporter expression showed differences in neuronal cell types between C. briggsae and C. elegans, indicating evolutionary changes in lin-11 regulation between the two species. Reciprocal transformation experiments provided further evidence consistent with functional changes in both cis and trans regulation of lin-11. To further investigate transcriptional regulation of lin-11, we dissected the intronic regions in C. elegans and identified cell-specific enhancers. These enhancers possess multiple sequence blocks that are conserved among Caenorhabditis species and possess TF binding sites. We tested the role of a subset of predicted TFs and discovered that while three of them (SKN-1, CEH-6, and CRH-1) act via the intron 3 enhancer to negatively regulate lin-11 expression in neurons, another TF (CES-1) acts positively via the intron 7 enhancer. Overall, our findings demonstrate that neuronal expression of lin-11 involves multiple TF regulators and regulatory modules some of which have diverged in Caenorhabditis nematodes.

  1. Testicular expression of the Lin28/let-7 system: Hormonal regulation and changes during postnatal maturation and after manipulations of puberty.

    PubMed

    Sangiao-Alvarellos, S; Manfredi-Lozano, M; Ruiz-Pino, F; León, S; Morales, C; Cordido, F; Gaytán, F; Pinilla, L; Tena-Sempere, M

    2015-10-23

    The Lin28/let-7 system, which includes the RNA-binding proteins, Lin28a/Lin28b, and let-7 miRNAs, has emerged as putative regulator of puberty and male gametogenesis; yet, its expression pattern and regulation in postnatal testis remain ill defined. We report herein expression profiles of Lin28 and let-7 members, and related mir-145 and mir-132, in rat testis during postnatal maturation and in models of altered puberty and hormonal deregulation. Neonatal expression of Lin28a and Lin28b was low and rose markedly during the infantile period; yet, expression patterns diverged thereafter, with persistently elevated levels only for Lin28b, which peaked at puberty. Let-7a, let-7b, mir-132 and mir-145 showed profiles opposite to Lin28b. In fact, let-7b and mir-145 were abundant in pachytene spermatocytes, but absent in elongating spermatids, where high expression of Lin28b was previously reported. Perturbation of puberty by neonatal estrogenization reverted the Lin28/let-7 expression ratio; expression changes were also detected in other models of delayed puberty, due to early photoperiod or nutritional manipulations. In addition, hypophysectomy or growth hormone (GH) deficiency revealed regulation of this system by gonadotropins and GH. Our data document the expression profiles of the Lin28/let-7 system in rat testis along postnatal/pubertal maturation, and their perturbation in models of pubertal and hormonal manipulation.

  2. Testicular expression of the Lin28/let-7 system: Hormonal regulation and changes during postnatal maturation and after manipulations of puberty

    PubMed Central

    Sangiao-Alvarellos, S.; Manfredi-Lozano, M.; Ruiz-Pino, F.; León, S.; Morales, C.; Cordido, F.; Gaytán, F.; Pinilla, L.; Tena-Sempere, M.

    2015-01-01

    The Lin28/let-7 system, which includes the RNA-binding proteins, Lin28a/Lin28b, and let-7 miRNAs, has emerged as putative regulator of puberty and male gametogenesis; yet, its expression pattern and regulation in postnatal testis remain ill defined. We report herein expression profiles of Lin28 and let-7 members, and related mir-145 and mir-132, in rat testis during postnatal maturation and in models of altered puberty and hormonal deregulation. Neonatal expression of Lin28a and Lin28b was low and rose markedly during the infantile period; yet, expression patterns diverged thereafter, with persistently elevated levels only for Lin28b, which peaked at puberty. Let-7a, let-7b, mir-132 and mir-145 showed profiles opposite to Lin28b. In fact, let-7b and mir-145 were abundant in pachytene spermatocytes, but absent in elongating spermatids, where high expression of Lin28b was previously reported. Perturbation of puberty by neonatal estrogenization reverted the Lin28/let-7 expression ratio; expression changes were also detected in other models of delayed puberty, due to early photoperiod or nutritional manipulations. In addition, hypophysectomy or growth hormone (GH) deficiency revealed regulation of this system by gonadotropins and GH. Our data document the expression profiles of the Lin28/let-7 system in rat testis along postnatal/pubertal maturation, and their perturbation in models of pubertal and hormonal manipulation. PMID:26494358

  3. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    PubMed

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Lin28A activates androgen receptor via regulation of c-myc and promotes malignancy of ER-/Her2+ breast cancer.

    PubMed

    Shen, Honghong; Zhao, Lin; Feng, Xiaolong; Xu, Cong; Li, Congying; Niu, Yun

    2016-09-13

    Having previously demonstrated the co-expression status of the Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, we tested the hypothesis that Lin28A can activate AR and promotes growth of ER-/Her2+ breast cancer. The expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid were transfected into ER-/Her2+ breast cancer cells. Chromatin immune-precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber invasion assays, colony formation assays and flow cytometry analysis were performed. ER-/Her2+ breast cancer cells which transfected with Lin28A siRNAs and Lin28A plasmid were injected into nude mice, and tumorigenesis was monitored. Our data showed that Lin28A can induced AR expression in ER-/Her2+ breast cancer cells. ChIP analysis showed that Lin28A stimulates the recruitment of c-Myc to the promoter of the AR gene. Lin28A enhanced growth ability, colonies ability, cells proliferation activities, invasive ability and inhibited cells apoptosis of ER-/Her2+ breast cancer cells. Lin28A high expression cells exhibited significantly higher tumorigenic ability in vivo. Our study demonstrates that Lin28A can activates androgen receptor via regulation of c-myc and promotes malignancy of ER-/Her2+ breast cancer. Our findings underline a novel role for Lin28A in breast cancer development and activation of the AR axis.

  5. Lin28A activates androgen receptor via regulation of c-myc and promotes malignancy of ER−/Her2+ breast cancer

    PubMed Central

    Shen, Honghong; Zhao, Lin; Feng, Xiaolong; Xu, Cong; Li, Congying; Niu, Yun

    2016-01-01

    Having previously demonstrated the co-expression status of the Lin28A and androgen receptor (AR) in ER−/Her2+ breast cancer, we tested the hypothesis that Lin28A can activate AR and promotes growth of ER−/Her2+ breast cancer. The expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid were transfected into ER−/Her2+ breast cancer cells. Chromatin immune-precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber invasion assays, colony formation assays and flow cytometry analysis were performed. ER−/Her2+ breast cancer cells which transfected with Lin28A siRNAs and Lin28A plasmid were injected into nude mice, and tumorigenesis was monitored. Our data showed that Lin28A can induced AR expression in ER−/Her2+ breast cancer cells. ChIP analysis showed that Lin28A stimulates the recruitment of c-Myc to the promoter of the AR gene. Lin28A enhanced growth ability, colonies ability, cells proliferation activities, invasive ability and inhibited cells apoptosis of ER−/Her2+ breast cancer cells. Lin28A high expression cells exhibited significantly higher tumorigenic ability in vivo. Our study demonstrates that Lin28A can activates androgen receptor via regulation of c-myc and promotes malignancy of ER−/Her2+ breast cancer. Our findings underline a novel role for Lin28A in breast cancer development and activation of the AR axis. PMID:27494865

  6. Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.

    PubMed

    Wang, Linbo; Yuan, Chao; Lv, Kezhen; Xie, Shuduo; Fu, Peifen; Liu, Xiaojiao; Chen, Yongxia; Qin, Chuan; Deng, Wuguo; Hu, Wenxian

    2013-01-01

    Resistance to radiation therapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to breast tumorigenesis; however, the relationship between Lin28 and radioresistance remains unknown. In this study, we investigated the association of Lin28 with radiation resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines. The results showed that the expression level of Lin28 was closely associated with resistance to radiation treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to radiation than MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which have low-level Lin28 expression. Transfection with Lin28 siRNA significantly led to an increase of sensitivity to radiation. By contrast, stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to radiation treatment. Stable expression of Lin28 also significantly inhibited radiation-induced apoptosis. Moreover, further studies have shown that caspases, H2A.X and Let-7 miRNA were the molecular targets of Lin28. Stable expression of Lin28 and treatment with radiation induced H2AX expression, while inhibited p21 and γ-H2A.X. Overexpression of Let-7 enhanced the sensitivities to radiation in breast cancer cells. Taken together, these results indicate that Lin28 might be one mechanism underlying radiation resistance, and Lin28 could be a potential target for overcoming radiation resistance in breast cancer.

  7. Improving systems documentation using an online copy editor

    SciTech Connect

    Kahn, R.L.

    1985-01-01

    For the last three years the author has been using Writers Workbench, a UNIX text-editing tool, to edit computer documentation. In this article the author outlines his experiences using the system, noting both the advantages to explore and pitfalls to avoid in using this tool. Writers Workbench is especially useful for improving a writer's basic skills - punctuation, spelling, and grammar. When used effectively, Writers Workbench can cut down on wordiness and improve the consistency of a manual. It can help in the creation of a table of contents, index, glossary, and bibliography and in checking readability. Furthermore, by creating user-defined dictionaries, authors or editors can customize the tool to fit their purposes and styles. However, Writers Workbench is not good at catching problems relating to organization, focus, and clarity.

  8. Highlighting impact: Do editors' selections identify influential papers?

    NASA Astrophysics Data System (ADS)

    Antonoyiannakis, Manolis

    A recent trend in scientific publishing is that journal editors highlight each week a select set among the papers published (usually) in their respective journals. The highlighted papers are deemed of higher quality, importance, or interest than the 'average' paper and feature prominently in the publishers' websites. We perform a citation analysis of the highlighted papers for a number of journals from various publishers in physics. By comparing the performance of highlighted papers relative to (a) typical papers and (b) highly cited papers in their source journals and in other journals in the field, we explore whether, and to what extent, the selection process at the time of publication identifies papers that will turn out to be influential. We discuss the broader implications for research assessment.

  9. A diagram editor for efficient biomedical knowledge capture and integration.

    PubMed

    Yu, Bohua; Jakupovic, Elvis; Wilson, Justin; Dai, Manhong; Xuan, Weijian; Mirel, Barbara; Athey, Brian; Watson, Stanley; Meng, Fan

    2008-03-01

    Understanding the molecular mechanisms underlying complex disorders requires the integration of data and knowledge from different sources including free text literature and various biomedical databases. To facilitate this process, we created the Biomedical Concept Diagram Editor (BCDE) to help researchers distill knowledge from data and literature and aid the process of hypothesis development. A key feature of BCDE is the ability to capture information with a simple drag-and-drop. This is a vast improvement over manual methods of knowledge and data recording and greatly increases the efficiency of the biomedical researcher. BCDE also provides a unique concept matching function to enforce consistent terminology, which enables conceptual relationships deposited by different researchers in the BCDE database to be mined and integrated for intelligible and useful results. We hope BCDE will promote the sharing and integration of knowledge from different researchers for effective hypothesis development.

  10. Upcoming IJTMB Initiatives from the Interim Executive Editor

    PubMed Central

    Kennedy, Ann Blair

    2016-01-01

    It is an honor and a privilege to be appointed the Interim Executive Editor for the IJTMB; I am lucky to have some initiatives that were already in development by the previous editorial team that I hope to bring to fruition over the next few months. First, I hope to increase the Journal’s Internet presence through social media to expand readership and encourage new submitters. The second initiative is a mentoring program to assist writers with their submissions to the Journal. Finally, I, and the rest of the editorial staff, will continue to evaluate the process, procedures, and forms used in peer review. I hope to move these initiatives forward and by doing so, bring in new readers, submitters, and reviewers to the Journal. PMID:27974945

  11. Educating science editors: is there a comprehensive strategy?

    PubMed Central

    Gasparyan, Armen Yuri; Yessirkepov, Marlen; Gorin, Sergey V.; Kitas, George D.

    2014-01-01

    The article considers available options to educate science editors in the fast-transforming digital environment. There is no single course or resource that can cover their constantly changing and diversifying educational needs. The involvement in research, writing, and reviewing is important for gaining editing skills, but that is not all. Membership in editorial associations and access to updated scholarly information in the field are mandatory for maintaining editorial credentials. Learned associations offer access to a few widely-recognized periodicals. There are also formal training courses covering issues in science writing and ethical editing, but no high-level evidence data exist to promote any of these. Networking with like-minded specialists within the global and regional editorial associations seems a useful strategy to upgrade editorial skills and resolve problems with the quality control and digitization of scholarly periodicals. PMID:25559840

  12. The X-windows interactive navigation data editor

    NASA Technical Reports Server (NTRS)

    Rinker, G. C.

    1992-01-01

    A new computer program called the X-Windows Interactive Data Editor (XIDE) was developed and demonstrated as a prototype application for editing radio metric data in the orbit-determination process. The program runs on a variety of workstations and employs pull-down menus and graphical displays, which allow users to easily inspect and edit radio metric data in the orbit data files received from the Deep Space Network (DSN). The XIDE program is based on the Open Software Foundation OSF/Motif Graphical User Interface (GUI) and has proven to be an efficient tool for editing radio metric data in the navigation operations environment. It was adopted by the Magellan Navigation Team as their primary data-editing tool. Because the software was designed from the beginning to be portable, the prototype was successfully moved to new workstation environments. It was also itegrated into the design of the next-generation software tool for DSN multimission navigation interactive launch support.

  13. An Internet-based ontology editor for medical appropriateness criteria.

    PubMed

    Kahn, C E

    1998-04-01

    Appropriateness criteria and practice guidelines seek to promote the cost-effectiveness use of medical interventions, and can be most useful when integrated with computer-based patient records and order-entry systems. Building an abstract model (ontology) of appropriateness criteria can require considerable effort among investigators at geographically dispersed institutions. To facilitate the construction and maintenance of ontologies for clinical appropriateness criteria, the author developed an Internet-based system for viewing and editing the knowledge model. The system, called NEON (Network-based Editor for ONtologies), uses the World Wide Web as a platform-independent user interface. NEON allows users to edit the indexing terms and the semantic network that form the ontology for a set of appropriateness criteria. Ontologies built using the system can be imported and exported using an open, internationally standardized format based on the Standard Generalized Markup Language (SGML).

  14. Andreae is New Editor of Global Biogeochemical Cycles

    NASA Astrophysics Data System (ADS)

    Andreae, Meinrat O.

    2004-10-01

    As the incoming editor of Global Biogeochemical Cycles, I would like to introduce myself and my ideas for the journal to Eos readers and to current and potential GBC authors. I've had a somewhat ``roaming'' scientific evolution, coming from ``straight'' chemistry through hard-rock geochemistry to chemical oceanography, the field in which I did my Ph.D. I taught marine chemistry at Florida State University for a number of years, and developed an interest in ocean/atmosphere interactions and atmospheric chemistry. In 1987 I took on my present job at the Max Planck Institute for Chemistry, in Mainz, Germany, and, after leaving the seacoast, my interests shifted to interactions between the terrestrial biosphere and atmosphere, including the role of vegetation fires. My present focus is on the role of biogenic aerosols and biomass smoke in regulating cloud properties and influencing climate.

  15. Advanced software development workstation project: Engineering scripting language. Graphical editor

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Software development is widely considered to be a bottleneck in the development of complex systems, both in terms of development and in terms of maintenance of deployed systems. Cost of software development and maintenance can also be very high. One approach to reducing costs and relieving this bottleneck is increasing the reuse of software designs and software components. A method for achieving such reuse is a software parts composition system. Such a system consists of a language for modeling software parts and their interfaces, a catalog of existing parts, an editor for combining parts, and a code generator that takes a specification and generates code for that application in the target language. The Advanced Software Development Workstation is intended to be an expert system shell designed to provide the capabilities of a software part composition system.

  16. EDITORIAL: A word from the new Editor-in-Chief A word from the new Editor-in-Chief

    NASA Astrophysics Data System (ADS)

    Mostowski, Jan

    2011-01-01

    TIn the autumn of 2010 I became the Editor-in Chief of European Journal of Physics (EJP). EJP is a place for teachers, instructors and professors to exchange their views on teaching physics at university level and share their experience. It is general opinion that no good research is possible without connection with good, high-quality teaching, at the university level in particular. Therefore excellence in physics teaching is important to the physics community. European Journal of Physics is proud of its contribution to achieving this goal. As Editor-in-Chief, I will continue to work to this general objective of the journal. We will publish articles on specific topics in physics, stressing originality of presentation and suitability for use in students'laboratories, lectures and physics teaching in general. We will also publish more pedagogical papers presenting the achievements of particular teaching methods. In addition, we will continue to publish special sections on particular areas of physics, as well as the annual special section on physics competitions. European Journal of Physics is in good shape. Due to the work of the previous editors and the publisher, the readership is high and growing steadily, and many excellent papers are being submitted and published. I hope that this positive trend for the journal will continue, and I will do my best to keep to this high standard. A few words about myself. I work in the Institute of Physics in Warsaw, Poland. My main research interests are in theoretical quantum optics and I have published about 80 research papers on this topic. For many years I was involved in teaching physics at university and in high school. I am a co-author of a textbook on physics for high-school students and of a problem book in quantum mechanics. For the last ten years, I have been involved in the International Physics Olympiad and over the last few years I have been a member of the Editorial Board of European Journal of Physics.

  17. A "Situational" and "Coorientational" Measure of Specialized Magazine Editors' Perceptions of Readers.

    ERIC Educational Resources Information Center

    Jeffers, Dennis W.

    A study was undertaken of specialized magazine editors' perceptions of audience characteristics as well as the perceived role of their publications. Specifically, the study examines the relationship between the editors' perceptions of reader problem recognition, level of involvement, constraint recognition, and possession of reference criteria and…

  18. Editorial Page Editors and Endorsements: Chain-owned vs. Independent Newspapers.

    ERIC Educational Resources Information Center

    St. Dizier, Byron

    Questionnaires were sent to 114 of the 228 editorial page editors at newspapers in the United States with daily circulations greater than 50,000 for a study that compared (1) the editor-publisher relationship existing at chains to that found at independent papers, and (2) the 1984 presidential endorsements made by chains to those by independent…

  19. Error Pattern Analysis Applied to Technical Writing: An Editor's Guide for Writers.

    ERIC Educational Resources Information Center

    Monagle, E. Brette

    The use of error pattern analysis can reduce the time and money spent on editing and correcting manuscripts. What is required is noting, classifying, and keeping a frequency count of errors. First an editor should take a typical page of writing and circle each error. After the editor has done a sufficiently large number of pages to identify an…

  20. Debunking the Mutilated Boy: A Study of Newspaper Editors and an Inflammatory Rumor.

    ERIC Educational Resources Information Center

    Brown, Lee

    A study examined how newspaper editors resolve issues relating to rumors--that is whether to cover stories which may turn out to be false. The "mutilated boy" rumor was chosen for its antiquity and endurance, its powerful theme, and its ability to create intense anxiety in a community. Thirty-three of the 86 editors who responded to the…

  1. A Coorientational Study of Food Public Relations Practitioners, Editors and Readers.

    ERIC Educational Resources Information Center

    Knodell, Joyce Elaine

    Survey data on newspaper food editors and newspaper readers were collected through a title-rating technique. Analysis of responses to 40 food titles and leads indicated three newspaper food-editor types: transitional, traditional, and "new guard." Food-page readers fell into two types: information oriented (nutritionists) and cooking…

  2. "Clones," Codes, and Conflicts of Interest in Cartooning: Cartoonists and Editors Look at Ethics.

    ERIC Educational Resources Information Center

    Riffe, Daniel; And Others

    A study examined differences between political cartoonists and op-ed page editors on both traditional ethical issues (such as conflicts of interest) and the special, style-related concerns of editorial cartoonists. Hypotheses proposed were that editors and cartoonists (1) would condemn "cloning" or copying, reflecting an ethical…

  3. A "Situational" and "Coorientational" Measure of Specialized Magazine Editors' Perceptions of Readers.

    ERIC Educational Resources Information Center

    Jeffers, Dennis W.

    A study was undertaken of specialized magazine editors' perceptions of audience characteristics as well as the perceived role of their publications. Specifically, the study examines the relationship between the editors' perceptions of reader problem recognition, level of involvement, constraint recognition, and possession of reference criteria and…

  4. Letter to the editor of TAAP, in response to letter from Anders et al.

    EPA Science Inventory

    To the Editor, Toxicology and Applied Pharmacology: We would like to address the letter to the editor submitted by Anders et al. regarding the substantive issues raised regarding our paper "Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physi...

  5. The Editor and Publisher as Public Official: The Ultimate Conflict of Interest.

    ERIC Educational Resources Information Center

    Sneed, Don

    A fifteen-item Likert scale and indepth personal interviews were used to collect data in a study that examined whether five individuals who held both the role of editor and public official were perceived as able to perform in a socially responsible manner as editors of their community newspapers in their estimation and in the estimation of a…

  6. Beacon Editor: Capturing Signal Transduction Pathways Using the Systems Biology Graphical Notation Activity Flow Language.

    PubMed

    Elmarakeby, Haitham; Arefiyan, Mostafa; Myers, Elijah; Li, Song; Grene, Ruth; Heath, Lenwood S

    2017-08-28

    The Beacon Editor is a cross-platform desktop application for the creation and modification of signal transduction pathways using the Systems Biology Graphical Notation Activity Flow (SBGN-AF) language. Prompted by biologists' requests for enhancements, the Beacon Editor includes numerous powerful features for the benefit of creation and presentation.

  7. A survey of orthopaedic journal editors determining the criteria of manuscript selection for publication

    PubMed Central

    2011-01-01

    Background To investigate the characteristics of editors and criteria used by orthopaedic journal editors in assessing submitted manuscripts. Methods Between 2008 to 2009 all 70 editors of Medline listed orthopaedic journals were approached prospectively with a questionnaire to determine the criteria used in assessing manuscripts for publication. Results There was a 42% response rate. There was 1 female editor and the rest were male with 57% greater than 60 years of age. 67% of the editors worked in university teaching hospitals and 90% of publications were in English. The review process differed between journals with 59% using a review proforma, 52% reviewing an anonymised manuscript, 76% using a routine statistical review and 59% of journals used 2 reviewers routinely. In 89% of the editors surveyed, the editor was able to overrule the final decision of the reviewers. Important design factors considered for manuscript acceptance were that the study conclusions were justified (80%), that the statistical analysis was appropriate (76%), that the findings could change practice (72%). The level of evidence (70%) and type of study (62%) were deemed less important. When asked what factors were important in the manuscript influencing acceptance, 73% cited an understandable manuscript, 53% cited a well written manuscript and 50% a thorough literature review as very important factors. Conclusions The editorial and review process in orthopaedic journals uses different approaches. There may be a risk of language bias among editors of orthopaedic journals with under-representation of non-English publications in the orthopaedic literature. PMID:21527007

  8. Editorial Page Editors and Endorsements: Chain-owned vs. Independent Newspapers.

    ERIC Educational Resources Information Center

    St. Dizier, Byron

    Questionnaires were sent to 114 of the 228 editorial page editors at newspapers in the United States with daily circulations greater than 50,000 for a study that compared (1) the editor-publisher relationship existing at chains to that found at independent papers, and (2) the 1984 presidential endorsements made by chains to those by independent…

  9. Letter to the editor of TAAP, in response to letter from Anders et al.

    EPA Science Inventory

    To the Editor, Toxicology and Applied Pharmacology: We would like to address the letter to the editor submitted by Anders et al. regarding the substantive issues raised regarding our paper "Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physi...

  10. Magazine Article Placement: How Editors, Regular Contributors, and Novice Writers Rate Query Letters.

    ERIC Educational Resources Information Center

    Jolliffe, Lee

    About 350,000 freelance magazine articles were purchased by magazine editors last year from the 22,000 freelancers and 225,000 would-be freelancers in the United States. A study examined the factors editors judge most important in selecting freelance magazine article proposals, using factor analysis and qualitative examination of persuasive…

  11. New Technology and the Writer/Editor Relationship: Shifting Electronic Realities.

    ERIC Educational Resources Information Center

    Endres, Kathleen L.; Schierhorn, Ann B.

    1995-01-01

    Examines the role new technology is playing in the magazine writer/editor relationship. Finds that editors report the new technology is affecting their relationship with writers, and that free-lancers are less apt to use expensive new technology than staff writers. (SR)

  12. Self-Interest and Scholarly Publication: The Dilemma of Researchers, Reviewers, and Editors

    ERIC Educational Resources Information Center

    Calabrese, Raymond L.; Roberts, Brian

    2004-01-01

    Academic misconduct in research is of growing concern to funding agencies, scholars, and academic journal editors. Scholarly publication has ethical implications researchers, reviewers, and journal editors. The theoretical background of the ethics of scholarly publication is explored as well as the use of a case study of an untenured researcher…

  13. 29 CFR 793.11 - Combination announcer, news editor and chief engineer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

  14. 29 CFR 793.11 - Combination announcer, news editor and chief engineer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

  15. 29 CFR 793.11 - Combination announcer, news editor and chief engineer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

  16. 29 CFR 793.11 - Combination announcer, news editor and chief engineer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

  17. Dr. Bruce Squires witnessed vast changes during tenure as CMAJ editor

    PubMed Central

    Sullivan, Patrick

    1996-01-01

    Dr. Bruce Squires retired in September after spending 10 years as editor of CMAJ. During his tenure the editor's responsibilities expanded greatly because of the CMA's foray into the publishing of medical books and additional journals and other publications. In this article, people who have worked with Squires reflect on his term with CMAJ. Imagesp570-a

  18. Adolescent Sexual Initiation through the Lens of Letters to the Editor Published in Polish Teenage Magazines

    ERIC Educational Resources Information Center

    Kopacz, Marek S.; Bajka-Kopacz, Aleksandra

    2012-01-01

    Almost all teenage magazines invite readers to submit questions concerning relationships, published as letters to the editor, popularly called "advice columns," often containing explicit questions about sexuality. This study aims to examine, firstly, how themes related to sexual initiation are presented in letters to the editor published…

  19. Adolescent Sexual Initiation through the Lens of Letters to the Editor Published in Polish Teenage Magazines

    ERIC Educational Resources Information Center

    Kopacz, Marek S.; Bajka-Kopacz, Aleksandra

    2012-01-01

    Almost all teenage magazines invite readers to submit questions concerning relationships, published as letters to the editor, popularly called "advice columns," often containing explicit questions about sexuality. This study aims to examine, firstly, how themes related to sexual initiation are presented in letters to the editor published…

  20. Response to Niklasson's comment on Lin, et al. (2012) : "the relation between postural movement and bilateral motor integration".

    PubMed

    Lin, Chin-Kai; Kuo, Bor-Chen; Wu, Huey-Min

    2014-10-01

    In the study of Lin, Wu, Lin, Wu, Wu, Kuo, and Yeung (2012 ), the relationship between the validity of postural movement and bilateral motor integration in terms of sensory integration theory was examined. Postural movement is the ability to use the antigravity postures required for stabilization of the neck, trunk and upper extremities via muscle co-contractions in the neck and upper extremities, and balance. Niklasson's (2013 ) comment argued that postural movement should include primitive reflexes in terms of the general abilities approach. Niklasson (2013 ) focused on the efficacy of the treatment rather than the theoretical frameworks implied in the therapeutic activities. For that purpose Lin, et al. (2012 ) used sensory integration as the theoretical foundation, and the relationship between postural movement and bilateral motor integration was assessed via empirical data. The result of Lin, et al. (2012 ) was offered as a theoretical reference for therapeutic activities.