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Sample records for nuclear association david

  1. 78 FR 60273 - David E. Cereghino, Idaho County Light & Power Cooperative Association, Inc.; Notice of Transfer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... Federal Energy Regulatory Commission David E. Cereghino, Idaho County Light & Power Cooperative... Idaho County Light & Power Cooperative Association, Inc. informed the Commission that the exemption from... transferred to Idaho County Light & Power Cooperative Association, Inc. The project is located on John...

  2. David Scott

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Dr. David R. Scott was appointed Director of NASA's Flight Research Center on April 18, 1975. From August 1973 he served as Deputy Director of FRC and was appointed acting director in January 1975. He is retired from the U.S. Air Force where he held the rank of Colonel. Dave left the NASA Dryden Flight Research Center on October 30, 1977 after the Center had been renamed in honor of Hugh L. Dryden. As a NASA astronaut, Scott flew on Gemini 8, Apollo 9 and was spacecraft commander of Apollo 15. When he left the astronaut corps in 1972, Scott was named Technical Assistant to the Apollo Program Manager at Johnson Space Center in Houston. Later he served as Special Assistant for Mission Operations and Government Funded Equipment. Dave earned a Bachelor of Science Degree from the United States Military Academy in 1954, standing fifth in a class of 633, and the degrees of Bachelor and Master of Science in Aeronautics and Astronautics from the Massachusetts Institute of Technology (MIT) in 1962. He was awarded an Honorary Doctorate of Astronautical Science from the University of Michigan in 1971. Dave has graduated from the Air Force Experimental Test Pilot School and Aerospace Research Pilot School. He has over 5,600 hours flying time along with 20 hours of extra vehicular activity (EVA) time. Dr. Scott is a Fellow of the American Astronautical Society; Associate Fellow of the American Institute of Aeronautics and Astronautics; a member of the Society of Experimental Test Pilots, Tau Beta Pi, Sigma Xi, and Sigma Gamma Tau. Among Dr. Scott's special honors are two NASA Distinguished Service Medals, the NASA Exceptional Service Medal, two Air Force Distinguished Service Medals, the Air Force Distinguished Flying Cross, the Air Force Association's David C. Schilling Trophy, and the Robert J. Collier Trophy for 1971.

  3. Interview with David Moore

    ERIC Educational Resources Information Center

    Rossman, Allan; Dietz, E. Jacquelin; Moor, David

    2013-01-01

    David Moore is Professor Emeritus of Statistics at Purdue University. He served as the first President of the International Association for Statistical Education (IASE) from 1993-1995 and as President of the American Statistical Association (ASA) in 1998. He is a Fellow of the ASA and of the IMS and was awarded the ASA's Founders Award in…

  4. Interview with David Moore

    ERIC Educational Resources Information Center

    Rossman, Allan; Dietz, E. Jacquelin; Moor, David

    2013-01-01

    David Moore is Professor Emeritus of Statistics at Purdue University. He served as the first President of the International Association for Statistical Education (IASE) from 1993-1995 and as President of the American Statistical Association (ASA) in 1998. He is a Fellow of the ASA and of the IMS and was awarded the ASA's Founders Award in…

  5. David Gale: Restless Pioneer

    ERIC Educational Resources Information Center

    Meyer, Walter

    2006-01-01

    David Gale was one of the mathematicians responsible for the modern form of the theory of duality in linear programming and the associated proof of the minimax theorem in the theory of games. He is a member of the National Academy of Sciences and is Professor Emeritus of Mathematics and Operations Research at the University of California at…

  6. David Gale: Restless Pioneer

    ERIC Educational Resources Information Center

    Meyer, Walter

    2006-01-01

    David Gale was one of the mathematicians responsible for the modern form of the theory of duality in linear programming and the associated proof of the minimax theorem in the theory of games. He is a member of the National Academy of Sciences and is Professor Emeritus of Mathematics and Operations Research at the University of California at…

  7. David Hartley's Newtonian neuropsychology.

    PubMed

    Smith, C U

    1987-04-01

    David Hartley's association psychology has been immensely influential. His vibrationist neurophysiology has, in contrast, been largely overlooked and forgotten. Hartley's vibration theory is examined. On the one hand it is shown how closely it is related to Sir Isaac Newton's mathematical physics and on the other how well it complements the association theory. The vibration theory, indeed, strongly influenced Hartley's associationist psychology and hence is of more than merely antiquarian interest. Although Hartley's understanding of the central nervous system has long been superseded, his general ideas prefigure some aspects of contemporary neurophysiology and philosophy of mind and thus provide a further reason for rescuing his vibrationism from oblivion.

  8. David Macaulay's Pyramid.

    ERIC Educational Resources Information Center

    Frew, Andrew W.

    1997-01-01

    Integrating literature and mathematics can be meaningful using David Macaulay's "Pyramid." This article provides an annotated bibliography of picture books, fiction, folk tales, nonfiction, videotapes, audio books, and CD-ROMs for grades 1-12 to support a unit on Egypt. Describes related math activities; and highlights a catalog of…

  9. Recollections of David Marr.

    PubMed

    Nishihara, H K

    2012-01-01

    David Marr came to MIT's Artificial Intelligence (AI) Lab in the early 1970s and energized the study of vision at the intersection of computer science, psychology, and neuroscience. As one of his first graduate students, I had the privilege of getting to know him and working with him during that heady period of AI research.

  10. David Baines: Rural Doctor, Lecturer, Dancer.

    ERIC Educational Resources Information Center

    Wisecarver, Charmaine

    1993-01-01

    Discusses the career of David Baines, an American Indian doctor who successfully integrates traditional and modern medicine. Describes problems faced by American Indian doctors, the tremendous amount of work involved in medical training, and problems associated with working in rural areas and trying to straddle two opposing cultures when…

  11. David Baines: Rural Doctor, Lecturer, Dancer.

    ERIC Educational Resources Information Center

    Wisecarver, Charmaine

    1993-01-01

    Discusses the career of David Baines, an American Indian doctor who successfully integrates traditional and modern medicine. Describes problems faced by American Indian doctors, the tremendous amount of work involved in medical training, and problems associated with working in rural areas and trying to straddle two opposing cultures when…

  12. 77 FR 66581 - Notice of Renewal of the Civil Nuclear Trade Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... associations from across the United States' civil nuclear supply chain. Dated: October 31, 2012. Edward A. O... 20230; phone 202- 482-1706 or email David.Kincaid@trade.gov . SUPPLEMENTARY INFORMATION: The...

  13. Obituary: David Stanley Evans, 1916-2004

    NASA Astrophysics Data System (ADS)

    Bash, Frank N.

    2005-12-01

    headquartered in Cape Town, South Africa. David had designed and built a Newtonian spectrograph for the 74-inch Radcliffe Telescope with which he measured the first southern galaxy redshifts. David and his family spent 1965-66 in Austin, Texas, where he was a National Science Foundation Senior Visiting Scientist at the University of Texas and McDonald Observatory. They moved permanently to Austin in 1968 and David became a Professor of Astronomy and Associate Director of McDonald Observatory at the University of Texas at Austin. At McDonald Observatory, R. E. Nather had devised a high-speed photometer capable of measuring millisecond time-scale changes in brightness and with Brian Warner, he invented "high-speed astronomy". This instrument caused Evans to revive his occultation program and, over the next twenty years, he produced the major part of the angular diameters of late-type stars with his students and collaborators. In addition, David and collaborators used the extensive collections of the University of Texas to write "Herschel at the Cape". David was also involved in observing the occultation of ? Sco by Jupiter in 1972 and in observing, during a solar eclipse in 1973, the gravitational deflections in the positions of stars whose light passes near to the Sun. The eclipse was observed from Mauritania, and the observations confirmed Einstein's prediction again. David Evans and his students studied late-type stars that have large star-spots and others that flare. In addition, they studied stars whose lunar occultation observations had revealed them to be double or even more than two stars. David Evans's major scientific contribution was an application of his stellar angular diameters to deduce the surface brightness of stars with the result that with suitable color indices one could use photometry to deduce the angular diameter of stars. This is applicable to stars which can never be occulted by the Moon, and its application to Cepheid variable stars has yielded their

  14. Laurance David Hall.

    PubMed

    Coxon, Bruce

    2011-01-01

    An account is given of the life, scientific contributions, and passing of Laurance David Hall (1938-2009), including his early history and education at the University of Bristol, UK, and the synthesis and NMR spectroscopy of carbohydrates and other natural products during ∼20 years of research and teaching at the University of British Columbia in Vancouver, Canada. Lists of graduate students, post-doctoral fellows, and sabbatical visitors are provided for this period. Following a generous endowment by Dr. Herchel Smith, Professor Hall built a new Department of Medicinal Chemistry at Cambridge University, UK, and greatly expanded his researches into the technology and applications of magnetic resonance imaging (MRI) and zero quantum NMR. MRI technology was applied both to medical problems such as the characterization of cartilage degeneration in knee joints, the measurement of ventricular function, lipid localization in animal models of atherosclerosis, paramagnetic metal complexes of polysaccharides as contrast agents, and studies of many other anatomical features, but also to several aspects of materials analysis, including food analyses, process control, and the elucidation of such physical phenomena as the flow of liquids through porous media, defects in concrete, and the visualization of fungal damage to wood. Professor Hall's many publications, patents, lectures, and honors and awards are described, and also his successful effort to keep the Asilomar facility in Pacific Grove, California as the alternating venue for the annual Experimental NMR Conference. Two memorial services for Professor Hall are remembered.

  15. Memories of David Kirzhnits

    NASA Astrophysics Data System (ADS)

    Bolotovsky, B. M.

    2013-06-01

    In the mid-1950s, a new staff member appeared at the Theory Division of the Physical Institute of the Academy of Sciences (FIAN): David Abramovich Kirzhnits. A Moscow State University alumnus, after graduation he had been assigned to a large defense plant in the city of Gorky, where he had worked for several years as an engineer. He was "liberated" from there by Igor Evgenyevich Tamm, our department head, who managed to transfer him to FIAN. Igor Evgenyevich knew D. A. Kirzhnits - they had met in Moscow before Kirzhnits finished university. At that time Kirzhnits was performing thesis work with professor A. S. Kompaneyets as academic adviser. At his adviser's suggestion, D. Kirzhnits consulted with I. E. Tamm on questions pertaining to the thesis topic. I. E. Tamm took a great liking for the diploma student, and he even wanted to recruit D. A. Kirzhnits for the Theory Division immediately after graduation. But at that time (1949) this proved impossible for several reasons. First, D. Kirzhnits was, as they say, an "invalid of the fifth group" - a Jew - which during those years of violent struggle against cosmopolitanismb often proved an obstacle in looking for work. Second, during the years of mass repressions D. Kirzhnits' father had been arrested on treason charges (according to the charges, he had wanted to sell the Far East to Japan). After intensive investigation his father was released, but he lived only a little longer. Reports of this also could have impeded his acceptance. Third, Igor Evgenyevich didn't have enough weight in officials' eyes at that time and so was unable to overcome "first" and "second."...

  16. Dynein light chain association sequences can facilitate nuclear protein import.

    PubMed

    Moseley, Gregory W; Roth, Daniela Martino; DeJesus, Michelle A; Leyton, Denisse L; Filmer, Richard P; Pouton, Colin W; Jans, David A

    2007-08-01

    Nuclear localization sequence (NLS)-dependent nuclear protein import is not conventionally held to require interaction with microtubules (MTs) or components of the MT motor, dynein. Here we report for the first time the role of sequences conferring association with dynein light chains (DLCs) in NLS-dependent nuclear accumulation of the rabies virus P-protein. We find that P-protein nuclear accumulation is significantly enhanced by its dynein light chain association sequence (DLC-AS), dependent on MT integrity and association with DLCs, and that P-protein-DLC complexes can associate with MT cytoskeletal structures. We also find that P-protein DLC-AS, as well as analogous sequences from other proteins, acts as an independent module that can confer enhancement of nuclear accumulation to proteins carrying the P-protein NLS, as well as several heterologous NLSs. Photobleaching experiments in live cells demonstrate that the MT-dependent enhancement of NLS-mediated nuclear accumulation by the P-protein DLC-AS involves an increased rate of nuclear import. This is the first report of DLC-AS enhancement of NLS function, identifying a novel mechanism regulating nuclear transport with relevance to viral and cellular protein biology. Importantly, this data indicates that DLC-ASs represent versatile modules to enhance nuclear delivery with potential therapeutic application.

  17. David Morrison on Lake Vostok

    NASA Image and Video Library

    Dr. David Morrison discusses the implications of research possibilities at Lake Vostok, one of the largest subglacial lakes located over two miles beneath the ice in Antarctica. The lake has been c...

  18. Climate changes associated with nuclear war

    NASA Technical Reports Server (NTRS)

    Toon, O. B.

    1986-01-01

    Nuclear war, featuring explosion of half the world arsenal of nuclear weapons, would cause urban and forest fires that would inject 20-650 megatons of smoke into the atmosphere. The Northern Hemisphere optical depth would increase to between 0.5-14. All models indicate an increase in optical depths, a large net radiation gain in the smoke layer, and an antigreenhouse effect at the surface. Significant global cooling would proceed, transforming the global climate to a large degree toward that of an airless world. Persisting deficiencies in the models are identified, noting research areas which would improve the accuracies of the predictions.

  19. Climate changes associated with nuclear war

    NASA Technical Reports Server (NTRS)

    Toon, O. B.

    1986-01-01

    Nuclear war, featuring explosion of half the world arsenal of nuclear weapons, would cause urban and forest fires that would inject 20-650 megatons of smoke into the atmosphere. The Northern Hemisphere optical depth would increase to between 0.5-14. All models indicate an increase in optical depths, a large net radiation gain in the smoke layer, and an antigreenhouse effect at the surface. Significant global cooling would proceed, transforming the global climate to a large degree toward that of an airless world. Persisting deficiencies in the models are identified, noting research areas which would improve the accuracies of the predictions.

  20. David's Understanding of Functions and Periodicity

    ERIC Educational Resources Information Center

    Gerson, Hope

    2008-01-01

    This is a study of David, a senior enrolled in a high school precalculus course. David's understandings of functions and periodicity was explored, through clinical interviews and contextualized through classroom observations. Although David's precalculus class was traditional his understanding of periodic functions was unconventional David engaged…

  1. Emergence of the nuclear industry and associated crime. Master's thesis

    SciTech Connect

    Vaught, J.W.

    1991-08-01

    Nuclear energy, in weapons production and electrical power generation, is a technology that has endured public scrutiny since the late 1940s. Societal acceptance of this industry has been affected by controversy in the following areas: health effects of exposure to radiation, possible consequences resulting from accidents, and nuclear nonproliferation. The literature review begins in Chapter 2 by examining the changing public perceptions of nuclear energy over the last forty years. Support for the ideals and practices of the industry has often wavered, due to media representation of incidents, accidents, and potential catastrophic events. The second part of the chapter highlights the crimes associated with nuclear energy in a chronological order of concern by nuclear industry security specialists. Research has found certain types of crime to be more prevalent during particular eras than others. Crimes instigated by spies, peace activists, terrorists, and the insider (employee) are reviewed, with an emphasis on insider crime.

  2. A novel family of plant nuclear envelope-associated proteins.

    PubMed

    Pawar, Vidya; Poulet, Axel; Détourné, Gwénaëlle; Tatout, Christophe; Vanrobays, Emmanuel; Evans, David E; Graumann, Katja

    2016-10-01

    This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain. AtNEAP proteins localise to the nuclear periphery as part of stable protein complexes, are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex. An A. thaliana cDNA library screen identified a putative transcription factor called AtbZIP18 as a novel interactor of AtNEAP1, which suggest a connection between NEAP and chromatin. An Atneap1 Atneap3 double-knockout mutant showed reduced root growth, and altered nuclear morphology and chromatin structure. Thus AtNEAPs are suggested as inner nuclear membrane-anchored coiled-coil proteins with roles in maintaining nuclear morphology and chromatin structure.

  3. David Hume on Competent Judges

    ERIC Educational Resources Information Center

    Eaton, Marcia Muelder

    2004-01-01

    This essay is the eighth in an occasional series on past treatments of major issues in arts education policy from antiquity through the twentieth century. The essay on which it is based, David Hume's "Of the Standard of Taste," originally published in 1757, is too extensive to be reprinted here, but it is easily accessible in the public…

  4. David Hume on Competent Judges

    ERIC Educational Resources Information Center

    Eaton, Marcia Muelder

    2004-01-01

    This essay is the eighth in an occasional series on past treatments of major issues in arts education policy from antiquity through the twentieth century. The essay on which it is based, David Hume's "Of the Standard of Taste," originally published in 1757, is too extensive to be reprinted here, but it is easily accessible in the public…

  5. A Reply from David Elkind.

    ERIC Educational Resources Information Center

    Elkind, David

    1989-01-01

    Replying to Robert H. Anderson's article in the same "Principal" issue, David Elkind defends his article against classroom rotation. Elkind strongly favors multiage grouping and team teaching, but views the real issue as departmentalization and rotation versus self-contained classrooms. Although multiage grouping and team teaching are…

  6. The association between nuclear receptors and ocular diseases.

    PubMed

    Liu, Ke; Zou, Chang; Qin, Bo

    2017-02-07

    Nuclear hormone receptors (NRs) are one of the most abundant transcription factors in the human cells. They regulate expression of genes via interactions with corresponding ligands, co-activators, and co-repressors. These molecular pathways play important roles in the development, cell differentiation, and physiologic and metabolic processes. Increasingly, targeting nuclear receptors is becoming a promising strategy for new drug development. The aim of this review is to discuss the association between nuclear receptors and eye development, and expand their role in various ocular diseases such as keratitis, cataract, glaucoma, uveitis, retinopathy, and ophthalmic tumors. Recent studies in this area are highlighted as well as future research directions and potential clinical applications. Finally, various strategies will be elucidated to inspire more targeted therapies for ocular diseases through the use of nuclear receptors.

  7. TTRAP is a novel PML nuclear bodies-associated protein

    SciTech Connect

    Xu Guanlan; Pan Yukun; Wang Bingyin; Huang Lu; Tian Ling; Xue Jinglun; Chen Jinzhong Jia, William

    2008-10-24

    PML nuclear body (PML NB) is an important macromolecular nuclear structure that is involved in many essential aspects of cellular function. Tens of proteins have been found in PML NBs, and promyelocytic leukemia protein (PML) has been proven to be essential for the formation of this structure. Here, we showed that TRAF and TNF receptor-associated protein (TTRAP) was a novel PML NBs-associated protein. TTRAP colocalized with three important PML NBs-associated proteins, PML, DAXX and Sp100 in the typical fashion of PML NBs. By yeast mating assay, TTRAP was identified to interact with these PML NBs-associated proteins. The transcription and expression of TTRAP could be induced by IFN-{gamma}, representing another common feature of PML NBs-associated proteins. These results would not only be important for understanding PML NBs but also be helpful in studying the TTRAP function in the future.

  8. Human Leukemia-Associated Anti-Nuclear Reactivity

    PubMed Central

    Klein, George; Steiner, Melita; Wiener, Francis; Klein, Eva

    1974-01-01

    A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological specificity and morphological appearance, although it is visualized by the same method. Serum from acute myeloid leukemia patients gave positive reactions in 73% of the cases. In acute lymphatic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, and Burkitt's lymphoma the sera were positive in 35, 14, 19, and 24%, respectively. Two of five polycythemia and two of eleven myeloma sera were also positive. Among 61 healthy controls, 58 were negative, whereas three showed a diffuse nuclear staining with a different pattern. Among 24 carcinoma patients, 18 were negative, whereas six gave a nuclear staining with a different, diffuse pattern. Sera from 20 patients who had recovered from infectious mononucleosis were all negative. In addition to the blasts of acute myeloid leukemia, a similar reactivity was seen with two Epstein-Barr virus DNA and EBNA-negative African lymphoma biopsies and in a short-lived tissue culture line derived from one of them. LANA could be a fetal or tissue-specific antigen, a virally determined antigen, or a specific form of anti-nuclear reactivity. Images PMID:4595570

  9. Honoring Jean-David Rochaix.

    PubMed

    Govindjee; Redding, Kevin

    2017-02-01

    We honor Jean-David Rochaix, an outstanding scholar of chloroplast biogenesis and photosynthesis, who received the prestigious Lifetime Achievement Award of the International Society of Photosynthesis Research at its 17th International Photosynthesis Congress held in Maastricht, The Netherlands (August 5-12, 2016). With this award he joins other major discoverers in the field of photosynthesis: Pierre Joliot (of France, 2013); Ulrich W. Heber* (of Germany, 2010) and Kenneth Sauer (of USA, 2010); Jan M. Anderson* (of Australia, 2007); and Horst T. Witt* (of Germany, 2004). See "Appendix 1" for the list of those who have received the ISPR Communication, Innovation, Calvin-Benson, and Hill awards.

  10. Identification of nuclear structural protein alterations associated with seminomas.

    PubMed

    Leman, Eddy S; Magheli, Ahmed; Yong, Koh Meng Aw; Netto, George; Hinz, Stefan; Getzenberg, Robert H

    2009-12-15

    Currently, there are no specific markers available for the early detection and for monitoring testicular cancer. Based upon an approach that targets nuclear structure, we have identified a set of proteins that are specific for seminomas, which may then have clinical utility for the disease. Utilizing samples obtained from men with no evidence of testicular cancer (n = 5) as well as those with seminomas (n = 6), nuclear matrix proteins were extracted and separated using a high-resolution two-dimensional electrophoresis gel system. The proteins were identified by mass spectrometry analysis. These analyses revealed seven nuclear matrix proteins associated with the normal testes, which did not appear in the seminomas. In the seminomas, four nuclear matrix proteins were identified to be associated with the disease that were absent in the normal testes. Mass spectrometric and immunoblot analyses of these proteins revealed that one of the proteins identified in the normal testes appears to be StAR-related lipid transfer protein 7 (StARD7). In the non-seminoma tissues, one of the identified proteins appears to be cell division protein kinase 10 (CDK10). Both StarD7 and CDK10 could potentially be involved in cell differentiation and growth, and thus may serve as potential targets for therapy of prognostication of seminomas. This is the first study to examine the role of nuclear structural proteins as potential biomarkers in testicular cancer. We are currently examining the roles of some of the identified proteins as potential biomarkers for the disease. (c) 2009 Wiley-Liss, Inc.

  11. The "O" Word: Issues in Outsourcing. Professional Associations React to the Challenge. Interviews with SLA's David Bender and AIIP's Jane Miller.

    ERIC Educational Resources Information Center

    Quint, Barbara

    1996-01-01

    The executive director of the Special Libraries Association (SLA) and the president of the Association of Independent Information Professionals (AIIP) answer questions about outsourcing information services. Relevant policy, vendor-client relationships, managerial considerations, and effects on libraries are discussed. Two sidebars offer 19…

  12. David Gordon Campbell Robertson: A Biographical Sketch

    NASA Astrophysics Data System (ADS)

    See, J. B.

    Emeritus Professor David Robertson of the Missouri University of Science and Technology was born in Dublin Ireland on 29 December 1941. His father was a merchant navy Captain who served during WWII and during David's early years his family lived in Dublin and Donegal where David went to the local elementary school. In 1954 he moved to London with his parents and attended Highgate School before commencing metallurgy at the Royal School of Mines, Imperial College, London in 1960.

  13. Distributed Access View Integrated Database (DAVID) system

    NASA Technical Reports Server (NTRS)

    Jacobs, Barry E.

    1991-01-01

    The Distributed Access View Integrated Database (DAVID) System, which was adopted by the Astrophysics Division for their Astrophysics Data System, is a solution to the system heterogeneity problem. The heterogeneous components of the Astrophysics problem is outlined. The Library and Library Consortium levels of the DAVID approach are described. The 'books' and 'kits' level is discussed. The Universal Object Typer Management System level is described. The relation of the DAVID project with the Small Business Innovative Research (SBIR) program is explained.

  14. Battling Creaticide: An Interview with David C. Berliner

    ERIC Educational Resources Information Center

    Ambrose, Don

    2012-01-01

    This article presents an interview with David C. Berliner, a Regents' Professor in the College of Education at Arizona State University. His books include "Educational Psychology," "The Manufactured Crisis," and "The Handbook of Educational Psychology." He has served as president of the American Educational Research Association and of the…

  15. Battling Creaticide: An Interview with David C. Berliner

    ERIC Educational Resources Information Center

    Ambrose, Don

    2012-01-01

    This article presents an interview with David C. Berliner, a Regents' Professor in the College of Education at Arizona State University. His books include "Educational Psychology," "The Manufactured Crisis," and "The Handbook of Educational Psychology." He has served as president of the American Educational Research Association and of the…

  16. Can Cosmopolitanism Work Religiously? A Response to David T. Hansen

    ERIC Educational Resources Information Center

    Ghiloni, Aaron J.

    2017-01-01

    This response to David T. Hansen's 2016 plenary address to the Religious Education Association tests the viability of educational cosmopolitanism for religious education. Using a Deweyan methodology of understanding an idea through its consequences, Hansen's proposal is analyzed using dialogues with interreligious and Islamic pedagogies. The…

  17. [Book review] Green engineering: environmentally conscious design, by David T. Allen and David R. Shonnard

    USGS Publications Warehouse

    Boustany, R.G.

    2002-01-01

    Review of: Green engineering: Environmentally conscious design / David T. Allen and David R. Shonnard / Prentice-Hall, Inc., One Lake Street, Upper Saddle River, NJ 07458. 2002. 552 pages. ISBN 0-13-061908-6.

  18. INTRODUCTION: David Sherrington as a mentor of young scientists

    NASA Astrophysics Data System (ADS)

    Goldbart, Paul M.

    2008-08-01

    the ones first developed in the setting of the Sherrington--Kirkpatrick model of spin glasses. What this small anecdote hints at is the vastness of the terrain over which research on spin glasses is having a deep and lasting impact. As scientists we are, I think it's fair to say, at least partially motivated by a desire to receive some recognition for our work, some evidence that it has been engaging and stimulating to others in the field. But David's work far transcends this model, being pivotal not only to researchers in the originally-intended domain of rather obscure magnetic alloys, but also far, far beyond: from neuroscience and biological information processing, to the social sciences, including economics, and on to probability theory, computer science, the next generation of optimization algorithms, and the entire field of complexity theory. Indeed, one can regard spin glasses in the guise of the Sherrington-Kirkpatrick model as a conceptual version of the silicon revolution: a curiosity-driven scientific endeavour that continues to catalyse utterly unanticipated progress over far-flung domains. David captured it all perfectly in the title of his 2001 Bakerian Lecture: 'Magnets, microchips, memories and markets: [the] statistical physics of complex systems.' Many of us would consider ourselves wonderfully fortunate if our work were to have just a small fraction of the impact that David's has. Moreover, the scientific panorama revealed by investigations stimulated by David's work is beautiful, shocking and inspiring, a panorama broader still than condensed matter theory or even physics itself. So, when our spirits are down and our brows furrowed by some painful integral or a bug in our computer code, let us remember to pause and revel in the astonishing confluence of scientific themes that the Sherrington-Kirkpatrick model and its associates capture. To echo a view I first heard from Giorgio Parisi: I'm not sure if there is anything more rich or surprising in

  19. A Star of David catenane

    NASA Astrophysics Data System (ADS)

    Leigh, David A.; Pritchard, Robin G.; Stephens, Alexander J.

    2014-11-01

    We describe the synthesis of a [2]catenane that consists of two triply entwined 114-membered rings, a molecular link. The woven scaffold is a hexameric circular helicate generated by the assembly of six tris(bipyridine) ligands with six iron(II) cations, with the size of the helicate promoted by the use of sulfate counterions. The structure of the ligand extension directs subsequent covalent capture of the catenane by ring-closing olefin metathesis. Confirmation of the Star of David topology (two rings, six crossings) is provided by NMR spectroscopy, mass spectrometry and X-ray crystallography. Extraction of the iron(II) ions with tetrasodium ethylenediaminetetraacetate affords the wholly organic molecular link. The self-assembly of interwoven circular frameworks of controlled size, and their subsequent closure by multiple directed covalent bond-forming reactions, provides a powerful strategy for the synthesis of molecular topologies of ever-increasing complexity.

  20. David Mechanic: Professional Zombie Hunter.

    PubMed

    Hafferty, Frederic W; Tilburt, Jon

    2016-08-01

    Within the fields of medicine and sociology, the descriptor "profession" (along with its brethren: profession, professionalization, and professionalism) has had a rich etymological history, with terms taking on different meanings at different times-sometimes trespassing into shibboleth and jargon. This etymological journey has co-evolved with the career of David Mechanic to whom this issue of the Journal of Health Politics, Policy and Law is devoted. We exploit a provocative metaphor applied to Mechanic's work on the challenges facing medicine as a profession as a playful exegesis on what we call "profession" to excavate an ensconced and encrusted domain of health jargon operating at the tensive interface of society and modern medical work.

  1. David Hubel and Torsten Wiesel.

    PubMed

    Hubel, David; Wiesel, Torsten

    2012-07-26

    While attending medical school at McGill, David Hubel developed an interest in the nervous system during the summers he spent at the Montreal Neurological Institute. After heading to the United States in 1954 for a Neurology year at Johns Hopkins, he was drafted by the army and was assigned to the Neuropsychiatry Division at the Walter Reed Hospital, where he began his career in research and did his first recordings from the visual cortex of sleeping and awake cats. In 1958, he moved to the lab of Stephen Kuffler at Johns Hopkins, where he began a long and fruitful collaboration with Torsten Wiesel. Born in Sweden, Torsten Wiesel began his scientific career at the Karolinska Institute, where he received his medical degree in 1954. After spending a year in Carl Gustaf Bernhard's laboratory doing basic neurophysiological research, he moved to the United States to be a postdoctoral fellow with Stephen Kuffler. It was at Johns Hopkins where he met David Hubel in 1958, and they began working together on exploring the receptive field properties of neurons in the visual cortex. Their collaboration continued until the late seventies. Hubel and Wiesel's work provided fundamental insight into information processing in the visual system and laid the foundation for the field of visual neuroscience. They have had many achievements, including--but not limited to--the discovery of orientation selectivity in visual cortex neurons and the characterization of the columnar organization of visual cortex through their discovery of orientation columns and ocular-dominance columns. Their work earned them the Nobel Prize for Physiology or Medicine in 1981, which they shared with Roger Sperry. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Structure and Function of Latency-Associated Nuclear Antigen

    PubMed Central

    Verma, S. C.; Lan, K.

    2011-01-01

    Latency-associated nuclear antigen (LANA) encoded by open reading frame 73 (ORF73) is the major latent protein expressed in all forms of KSHV-associated malignancies. LANA is a large (222–234 kDa) nuclear protein that interacts with various cellular as well as viral proteins. LANA has been classified as an oncogenic protein as it dysregulates various cellular pathways including tumor suppressor pathways associated with pRb and p53 and can transform primary rat embryo fibroblasts in cooperation with the cellular oncogene Hras. It associates with GSK-3β, an important modulator of Wnt signaling pathway leading to the accumulation of cytoplasmic β-catenin, which upregulates Tcf/Lef regulated genes after entering into the nucleus. LANA also blocks the expression of RTA, the reactivation transcriptional activator, which is critical for the latency to lytic switch, and thus helps in maintaining viral latency. LANA tethers the viral episomal DNA to the host chromosomes by directly binding to its cognate binding sequence within the TR region of the genome through its C terminus and to the nucleosomes through the N terminus of the molecule. Tethering to the host chromosomes helps in efficient partitioning of the viral episomes in the dividing cells. Disruptions of LANA expression led to reduction in the episomal copies of the viral DNA, supporting its role in persistence of the viral DNA. The functions known so far suggest that LANA is a key player in KSHV-mediated pathogenesis. PMID:17089795

  3. David L. Harrison: A Work Of Art

    ERIC Educational Resources Information Center

    Raymond, Allen

    2005-01-01

    This article describes poet and writer David L. Harrison. A former School Board Chairman from Springfield, MO, David was responsible for beginning an annual "Teacher Appreciation Banquet" and for launching the "Sky High for Reading" program. The "Sky High for Reading" program encourages children in Springfield to read enough books so that, if…

  4. David L. Harrison: A Work Of Art

    ERIC Educational Resources Information Center

    Raymond, Allen

    2005-01-01

    This article describes poet and writer David L. Harrison. A former School Board Chairman from Springfield, MO, David was responsible for beginning an annual "Teacher Appreciation Banquet" and for launching the "Sky High for Reading" program. The "Sky High for Reading" program encourages children in Springfield to read enough books so that, if…

  5. Akinetic mutism and the story of David.

    PubMed

    Sinden, Rebecca; Wilson, Barbara A; Rose, Anita; Mistry, Nimisha

    2017-02-02

    Following a description about the characteristics of akinetic mutism (AM) and how it differs from locked-in syndrome (LIS) and a disorder of consciousness (DOC), we present the case of David, a 71-year-old man with AM. David sustained a stroke following a middle cerebral artery (MCA) thrombus. A CT scan at the time detected old ischaemic infarcts affecting the right frontal lobe, the left occipital lobe and the left parietal lobe so David had bilateral brain damage. Initially thought to have a DOC, further neuropsychological assessments administered when David had improved a little, resulted in the diagnosis of AM. Although David spoke little, when he did speak, his words and phrases were well articulated, grammatical and with appropriate intonation. He was alert and visually aware and he was not paralysed. We discuss whether the diagnosis was correct and address the difficulties in assessing such patients.

  6. Detection of special nuclear materials with the associate particle technique

    NASA Astrophysics Data System (ADS)

    Carasco, Cédric; Deyglun, Clément; Pérot, Bertrand; Eléon, Cyrille; Normand, Stéphane; Sannié, Guillaume; Boudergui, Karim; Corre, Gwenolé; Konzdrasovs, Vladimir; Pras, Philippe

    2013-04-01

    In the frame of the French trans-governmental R&D program against chemical, biological, radiological, nuclear and explosives (CBRN-E) threats, CEA is studying the detection of Special Nuclear Materials (SNM) by neutron interrogation with fast neutrons produced by an associated particle sealed tube neutron generator. The deuterium-tritium fusion reaction produces an alpha particle and a 14 MeV neutron almost back to back, allowing tagging neutron emission both in time and direction with an alpha particle position-sensitive sensor embedded in the generator. Fission prompt neutrons and gamma rays induced by tagged neutrons which are tagged by an alpha particle are detected in coincidence with plastic scintillators. This paper presents numerical simulations performed with the MCNP-PoliMi Monte Carlo computer code and with post processing software developed with the ROOT data analysis package. False coincidences due to neutron and photon scattering between adjacent detectors (cross talk) are filtered out to increase the selectivity between nuclear and benign materials. Accidental coincidences, which are not correlated to an alpha particle, are also taken into account in the numerical model, as well as counting statistics, and the time-energy resolution of the data acquisition system. Such realistic calculations show that relevant quantities of SNM (few kg) can be distinguished from cargo and shielding materials in 10 min acquisitions. First laboratory tests of the system under development in CEA laboratories are also presented.

  7. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies.

    PubMed

    Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

    2015-03-21

    Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB's function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB's role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy.

  8. Heterogeneous distributed query processing: The DAVID system

    NASA Technical Reports Server (NTRS)

    Jacobs, Barry E.

    1985-01-01

    The objective of the Distributed Access View Integrated Database (DAVID) project is the development of an easy to use computer system with which NASA scientists, engineers and administrators can uniformly access distributed heterogeneous databases. Basically, DAVID will be a database management system that sits alongside already existing database and file management systems. Its function is to enable users to access the data in other languages and file systems without having to learn the data manipulation languages. Given here is an outline of a talk on the DAVID project and several charts.

  9. Nuclear attitudes and reactions: associations with depression, drug use, and quality of life

    SciTech Connect

    Newcomb, M.D.

    1986-05-01

    For 40 years the world has lived with the threat of nuclear war and, recently, with the possibility of nuclear power plant accidents. Although virtually every generation must confront various national or international crises, the threat of nuclear war is unprecedented in its destructive potential. This study is an attempt to assess attitudes and amount of distress associated with the ever-present threat of nuclear war and the possibility of accidents at nuclear power plants. The Nuclear Attitudes Questionnaire (NAQ) consists of 15 items and was administered to 722 young adults who have grown up in the nuclear age. The items were found to reflect four latent factors of nuclear concern, nuclear support, fear of the future, and nuclear denial, all of which in turn represent a second-order construct of nuclear anxiety. Women reported significantly more nuclear concern, less nuclear support, more fear of the future, and less nuclear denial than did men. In latent-variable models, nuclear anxiety was found to be significantly associated with less purpose in life, less life satisfaction, more powerlessness, more depression, and more drug use. It is concluded that the threat of nuclear war and accidents is significantly related to psychological distress and may disturb normal maturational development.

  10. Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes.

    PubMed

    Rappa, Germana; Santos, Mark F; Green, Toni M; Karbanová, Jana; Hassler, Justin; Bai, Yongsheng; Barsky, Sanford H; Corbeil, Denis; Lorico, Aurelio

    2017-02-28

    Extracellular membrane vesicles (EVs) function as vehicles of intercellular communication, but how the biomaterials they carry reach the target site in recipient cells is an open question. We report that subdomains of Rab7+ late endosomes and nuclear envelope invaginations come together to create a sub-nuclear compartment, where biomaterials associated with CD9+ EVs are delivered. EV-derived biomaterials were also found in the nuclei of host cells. The inhibition of nuclear import and export pathways abrogated the nuclear localization of EV-derived biomaterials or led to their accumulation therein, respectively, suggesting that their translocation is dependent on nuclear pores. Nuclear envelope invagination-associated late endosomes were observed in ex vivo biopsies in both breast carcinoma and associated stromal cells. The transcriptome of stromal cells exposed to cancer cell-derived CD9+ EVs revealed that the regulation of eleven genes, notably those involved in inflammation, relies on the nuclear translocation of EV-derived biomaterials. Our findings uncover a new cellular pathway used by EVs to reach nuclear compartment.

  11. Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes

    PubMed Central

    Rappa, Germana; Santos, Mark F.; Green, Toni M.; Karbanová, Jana; Hassler, Justin; Bai, Yongsheng; Barsky, Sanford H.; Corbeil, Denis; Lorico, Aurelio

    2017-01-01

    Extracellular membrane vesicles (EVs) function as vehicles of intercellular communication, but how the biomaterials they carry reach the target site in recipient cells is an open question. We report that subdomains of Rab7+ late endosomes and nuclear envelope invaginations come together to create a sub-nuclear compartment, where biomaterials associated with CD9+ EVs are delivered. EV-derived biomaterials were also found in the nuclei of host cells. The inhibition of nuclear import and export pathways abrogated the nuclear localization of EV-derived biomaterials or led to their accumulation therein, respectively, suggesting that their translocation is dependent on nuclear pores. Nuclear envelope invagination-associated late endosomes were observed in ex vivo biopsies in both breast carcinoma and associated stromal cells. The transcriptome of stromal cells exposed to cancer cell-derived CD9+ EVs revealed that the regulation of eleven genes, notably those involved in inflammation, relies on the nuclear translocation of EV-derived biomaterials. Our findings uncover a new cellular pathway used by EVs to reach nuclear compartment. PMID:28129640

  12. Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene.

    PubMed Central

    DeHoratius, C; Silver, P A

    1996-01-01

    To identify components involved in nuclear protein import, we used a genetic selection to isolate mutants that mislocalized a nuclear-targeted protein. We identified temperature-sensitive mutants that accumulated several different nuclear proteins in the cytoplasm when shifted to the semipermissive temperature of 30 degrees C; these were termed npl (nuclear protein localization) mutants. We now present the properties of yeast strains bearing mutations in the NPL4 gene and report the cloning of the NPL4 gene and the characterization of the Np14 protein. The npl4-1 mutant was isolated by the previously described selection scheme. The second allele, npl4-2, was identified from an independently derived collection of temperature-sensitive mutants. The npl4-1 and npl4-2 strains accumulate nuclear-targeted proteins in the cytoplasm at the nonpermissive temperature consistent with a defect in nuclear protein import. Using an in vitro nuclear import assay, we show that nuclei prepared from temperature-shifted npl4 mutant cells are unable to import nuclear-targeted proteins, even in the presence of cytosol prepared from wild-type cells. In addition, npl4-2 cells accumulate poly(A)+ RNA in the nucleus at the nonpermissive temperature, consistent with a failure to export mRNA from the nucleus. The npl4-1 and npl4-2 cells also exhibit distinct, temperature-sensitive structural defects: npl4-1 cells project extra nuclear envelope into the cytoplasm, whereas npl4-2 cells from nuclear envelope herniations that appear to be filled with poly(A)+ RNA. The NPL4 gene encodes an essential M(r) 64,000 protein that is located at the nuclear periphery and localizes in a pattern similar to nuclear pore complex proteins. Taken together, these results indicate that this gene encodes a novel nuclear pore complex or nuclear pore complex-associated component required for nuclear membrane integrity and nuclear transport. Images PMID:8930904

  13. Nuclear cardiology core syllabus of the European Association of Cardiovascular Imaging (EACVI).

    PubMed

    Gimelli, Alessia; Neglia, Danilo; Schindler, Thomas H; Cosyns, Bernard; Lancellotti, Patrizio; Kitsiou, Anastasia

    2015-04-01

    The European Association of Cardiovascular Imaging (EACVI) Core Syllabus for Nuclear Cardiology is now available online. The syllabus lists key elements of knowledge in nuclear cardiology. It represents a framework for the development of training curricula and provides expected knowledge-based learning outcomes to the nuclear cardiology trainees.

  14. Polyadenylylated nuclear RNA encoded by Kaposi sarcoma-associated herpesvirus.

    PubMed Central

    Sun, R; Lin, S F; Gradoville, L; Miller, G

    1996-01-01

    A newly recognized gamma herpesvirus known as Kaposi sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is present in Kaposi sarcomas and body-cavity-based lymphomas. Here we identify a novel abundant 1.2-kb RNA, polyadenylated nuclear RNA (PAN RNA), encoded by the virus. The majority of cDNAs produced from poly(A)-selected RNA isolated from a human body cavity lymphoma cell line 48 hr after butyrate induction of KSHV lytic replication represented PAN RNA. Within PAN RNA were two 9 and 16 nt stretches with 89% and 94% identity to U1 RNA. A third stretch of 14 nt was 93% complementary to U1. The 5' upstream region of PAN RNA contained both proximal and distal sequence elements characteristic of regulatory regions of U snRNAs, whereas the 3' end was polyadenylylated. PAN RNA was transcribed by RNA polymerase II, lacked a trimethylguanosine cap, and did not associate with polyribosomes. PAN RNA formed a speckled pattern in the nucleus typical of U snRNAs and colocalized with Sm protein. Therefore, PAN represents a new type of RNA, possessing features of both U snRNA and mRNA. Images Fig. 2 Fig. 3 Fig. 4 PMID:8876232

  15. Dangers associated with civil nuclear power programmes: weaponization and nuclear waste.

    PubMed

    Boulton, Frank

    2015-07-24

    The number of nuclear power plants in the world rose exponentially to 420 by 1990 and peaked at 438 in 2002; but by 2014, as closed plants were not replaced, there were just 388. In spite of using more renewable energy, the world still relies on fossil fuels, but some countries plan to develop new nuclear programmes. Spent nuclear fuel, one of the most dangerous and toxic materials known, can be reprocessed into fresh fuel or into weapons-grade materials, and generates large amounts of highly active waste. This article reviews available literature on government and industry websites and from independent analysts on world energy production, the aspirations of the 'new nuclear build' programmes in China and the UK, and the difficulties in keeping the environment safe over an immense timescale while minimizing adverse health impacts and production of greenhouse gases, and preventing weaponization by non-nuclear-weapons states acquiring civil nuclear technology.

  16. Nuclear processes associated with peculiar A-type stars.

    NASA Technical Reports Server (NTRS)

    Cameron, A. G. W.

    1971-01-01

    A discussion is given of the various roles that nuclear reactions may play in production of anomalous abundances of elements in peculiar A stars. The effects which may be expected to occur both in the surface nuclear reactions and in some possible internal reactions that can occur in advanced stages of stellar evolution are considered. It is suggested that various features of peculiar A stars may require simultaneous operation of two or more of the processes of surface diffusion, surface nuclear reactions, and internal nuclear reactions.

  17. Association of Chromosome Territories with the Nuclear Matrix

    PubMed Central

    Ma, Hong; Siegel, Alan J.; Berezney, Ronald

    1999-01-01

    To study the possible role of the nuclear matrix in chromosome territory organization, normal human fibroblast cells are treated in situ via classic isolation procedures for nuclear matrix in the absence of nuclease (e.g., DNase I) digestion, followed by chromosome painting. We report for the first time that chromosome territories are maintained intact on the nuclear matrix. In contrast, complete extraction of the internal nuclear matrix components with RNase treatment followed by 2 M NaCl results in the disruption of higher order chromosome territory architecture. Correlative with territorial disruption is the formation of a faint DNA halo surrounding the nuclear lamina and a dispersive effect on the characteristically discrete DNA replication sites in the nuclear interior. Identical results were obtained using eight different human chromosome paints. Based on these findings, we developed a fractionation strategy to release the bulk of nuclear matrix proteins under conditions where the chromosome territories are maintained intact. A second treatment results in disruption of the chromosome territories in conjunction with the release of a small subset of acidic proteins. These proteins are distinct from the major nuclear matrix proteins and may be involved in mediating chromosome territory organization. PMID:10444063

  18. Instrument and spacecraft faults associated with nuclear radiation in space

    NASA Technical Reports Server (NTRS)

    Trainos, J. H.

    1994-01-01

    A review is given which surveys the variety of faults and failures which have occurred in space due both to the effects of single, energetic nuclear particles, as well as effects due to the accumulated ionizing dose or the fluence of nuclear particles. The review covers a variety of problems with sensors, electronics, instruments and spacecraft from several countries.

  19. Constructibility issues associated with a nuclear waste repository in basalt

    SciTech Connect

    Turner, D.A.

    1981-12-04

    This report contains the text and slide reproductions of a speech on nuclear waste disposal in basalt. The presentation addresses the layout of repository access shafts and subsurface facilities resulting from the conceptual design of a nuclear repository in basalt. The constructibility issues that must be resolved prior to construction are described. (DMC)

  20. p95vav associates with the nuclear protein Ku-70.

    PubMed Central

    Romero, F; Dargemont, C; Pozo, F; Reeves, W H; Camonis, J; Gisselbrecht, S; Fischer, S

    1996-01-01

    The proto-oncogene vav is expressed solely in hematopoietic cells and plays an important role in cell signaling, although little is known about the proteins involved in these pathways. To gain further information, the Src homology 2 (SH2) and 3 (SH3) domains of Vav were used to screen a lymphoid cell cDNA library by the yeast two-hybrid system. Among the positive clones, we detected a nuclear protein, Ku-70, which is the DNA-binding element of the DNA-dependent protein kinase. In Jurkat and UT7 cells, Vav is partially localized in the nuclei, as judged from immunofluorescence and confocal microscopy studies. By using glutathione S-transferase fusion proteins derived from Ku-70 and coimmunoprecipitation experiments with lysates prepared from human thymocytes and Jurkat and UT7 cells, we show that Vav associates with Ku-70. The interaction of Vav with Ku-70 requires only the 150-residue carboxy-terminal portion of Ku-70, which binds to the 25 carboxy-terminal residues of the carboxy SH3 domain of Vav. A proline-to-leucine mutation in the carboxy SH3 of Vav that blocks interaction with proline-rich sequences does not modify the binding of Ku-70, which lacks this motif. Therefore, the interaction of Vav with Ku-70 may be a novel form of protein-protein interaction. The potential role of Vav/Ku-70 complexes is discussed. PMID:8524317

  1. Mitochondrial regulation of cancer associated nuclear DNA methylation

    SciTech Connect

    Xie Chenghui; Naito, Akihiro; Mizumachi, Takatsugu; Evans, Teresa T.; Douglas, Michael G.; Cooney, Craig A.; Fan Chunyang; Higuchi, Masahiro

    2007-12-21

    The onset and progression of cancer is associated with the methylation-dependent silencing of specific genes, however, the mechanism and its regulation have not been established. We previously demonstrated that reduction of mitochondrial DNA content induces cancer progression. Here we found that mitochondrial DNA-deficient LN{rho}0-8 activates the hypermethylation of the nuclear DNA promoters including the promoter CpG islands of the endothelin B receptor, O{sup 6}-methylguanine-DNA methyltransferase, and E-cadherin. These are unmethylated and the corresponding gene products are expressed in the parental LNCaP containing mitochondrial DNA. The absence of mitochondrial DNA induced DNA methyltransferase 1 expression which was responsible for the methylation patterns observed. Inhibition of DNA methyltransferase eliminated hypermethylation and expressed gene products in LN{rho}0-8. These studies demonstrate loss or reduction of mitochondrial DNA resulted in the induction of DNA methyltransferase 1, hypermethylation of the promoters of endothelin B receptor, O{sup 6}-methylguanine-DNA methyltransferase, and E-cadherin, and reduction of the corresponding gene products.

  2. The Emergence of the Nuclear Industry and Associated Crime

    DTIC Science & Technology

    1991-08-01

    was Martin Sobell, who was convicted and sentenced to thirty years in prison. He was confined for five years at Alcatraz and was later transferred to...Washington: GPO, 1973): 111-1. 11 Dan O’Niel, "Project Chariot: How Alaska Escaped Nuclear Excavation," The Bulletin of thg Atomic Scientists 45, no...Chariot: How Alaska Escaped Nuclear Excavation." The Bulletin of the Atomic Scientists 45, no. 10 (1989): 28-37. Otway, Harry J., Dagmar Maurer, and

  3. David A. Wright in ER-2

    NASA Image and Video Library

    1999-10-27

    David A. Wright is associate director for Center Operations at the NASA Dryden Flight Research Center, Edwards, Calif. He was formerly director of Flight Operations. He is also a research pilot, flying NASA's ER-2 and T-38. The ER-2s are civilian variants of the military U-2S reconnaissance aircraft and carry scientific instruments to study the Earth during worldwide deployments. Wright has more than 4,500 hours in six different aircraft. He held the position of deputy director of the Airborne Science Program at Dryden from 2002 until 2004. Wright came to Dryden after retiring from the U.S. Air Force as a lieutenant colonel. His final assignment was to the Joint Staff J3, Directorate of Operations at the Pentagon from November 1996 until August 1999. Prior to the Pentagon assignment, he served as commander of the 1st Reconnaissance Squadron at Beale Air Force Base near Marysville, Calif., the unit responsible for training all U-2 pilots. He was the operations officer for one the largest U-2 operations in history, flying combat missions against Iraq and managing an unprecedented U-2 flying schedule during the 1991 Desert Storm conflict. He was selected for the Air Force U-2 program in 1987 following duty as an aircraft commander in the E-3A AWACS (Airborne Warning and Control System) aircraft. Wright was a T-38 instructor for three years at Reese Air Force Base, Lubbock, Texas, following completion of pilot training in 1978. He graduated from the U.S. Air Force Academy in 1977 with a Bachelor of Science in mathematics and computer science. Wright earned a Master of Arts in Adult Education from Troy State University, Montgomery, Ala., in 1987, and a Master of Science in National Security and Strategic Studies from the Naval War College, Newport, R.I., in 1995.

  4. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations.

    PubMed

    Bellanné-Chantelot, Christine; Chauveau, Dominique; Gautier, Jean-François; Dubois-Laforgue, Danièle; Clauin, Séverine; Beaufils, Sandrine; Wilhelm, Jean-Marie; Boitard, Christian; Noël, Laure-Hélène; Velho, Gilberto; Timsit, José

    2004-04-06

    Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene, mostly generating truncated protein. Various phenotypes, including urogenital malformations, are related to HNF-1beta mutations. To describe clinical and genetic findings in 13 patients with 8 novel HNF-1beta mutations. Multicenter, descriptive study. 2 departments of diabetes, 1 department of internal medicine, and 1 department of nephrology. 8 probands with diabetes diagnosed before 40 years of age and nondiabetic kidney disease who were selected independent of their family history of diabetes, and 5 offspring. Characteristics of diabetes, renal function and structure, genital tract abnormalities, pancreas structure, insulin secretion, exocrine pancreas function, and liver test results. All mutations, including 5 missense changes, were found in the DNA-binding domain. Cosegregation of the mutation and MODY5 phenotype was observed in 4 families. Occurrence of a de novo mutation was demonstrated in 2 families. Diabetes was present in 10 of 13 mutation carriers. It was clinically overt in 5 participants and found by screening at age 19 to 38 years in 5 participants. Pancreas atrophy was observed in 5 of 6 probands, and pancreas exocrine insufficiency was observed in 6 of 7 probands. Renal involvement, consisting of structural changes and slowly progressive renal failure, was recognized in 9 patients at 18 to 41 years of age. Dysplastic kidneys were found by ultrasonography in 3 fetuses who subsequently showed transient neonatal renal failure. Genital tract abnormalities were present in 5 probands and liver enzyme levels were abnormal in 11 of 13 patients. Since the study was small and not population-based, it could not estimate the prevalence of MODY5. Other phenotypes might be associated with HNF-1beta mutations. Maturity-onset diabetes of the young type 5

  5. Family Matters: A Conversation with David Popenoe

    ERIC Educational Resources Information Center

    Iannone, Carol

    2009-01-01

    This article presents an interview with Professor David Popenoe, author of the controversial book "Disturbing the Nest: Family Change and Decline in Modern Societies" (1988). Popenoe heads the National Marriage Project at Rutgers University, where he taught sociology for forty-five years until his recent retirement. Here, Popenoe discusses his…

  6. A Conversation with...David Satcher.

    ERIC Educational Resources Information Center

    Campbell, Neil A.

    1996-01-01

    David Satcher began his career as a medical geneticist and was appointed director of the Centers for Disease Control and Prevention (CDC) in 1993. In this interview, Dr. Satcher talks about the responsibilities of the CDC and explains how a childhood experience inspired his interest in medicine and his continuing commitment to community service.…

  7. Family Matters: A Conversation with David Popenoe

    ERIC Educational Resources Information Center

    Iannone, Carol

    2009-01-01

    This article presents an interview with Professor David Popenoe, author of the controversial book "Disturbing the Nest: Family Change and Decline in Modern Societies" (1988). Popenoe heads the National Marriage Project at Rutgers University, where he taught sociology for forty-five years until his recent retirement. Here, Popenoe discusses his…

  8. Another Perspective: An Interview with David Smith

    ERIC Educational Resources Information Center

    Bowman, Ruth A.; Johnson, Kelli

    2005-01-01

    To provide another perspective on evaluation within nonformal settings, "New Directions for Evaluation" recently interviewed David Smith, the coordinator of the Professional Learning to Close the Achievement Gap program for the Kansas City, Kansas, Public Schools, who has extensive background in education and educational research. He formerly held…

  9. David Ben-Gurion: A Creative Leader

    ERIC Educational Resources Information Center

    Rosemarin, Shoshana

    2014-01-01

    David Ben-Gurion (1886-1973), the first Prime Minister of Israel, is included in Pasternak's (2001) list of the nine most memorable leaders of the twentieth century. All of them are remembered for the reforms they initiated. Roosevelt (USA), Stalin (Russia), Castro (Cuba), and Thatcher (England) focused on social-economical changes, whereas Gandhi…

  10. A Case of You: Remembering David Fowler

    ERIC Educational Resources Information Center

    Pimm, David

    2004-01-01

    The author has framed this brief appreciation of David Flower in terms of influence; specifically, his influence as a teacher, both in person and through his writing (most of all his attempted rewriting of much of the history of Greek mathematics). The author will also make some second-order remarks about the influence of teachers.

  11. Exploring the Living Planet with David Attenborough.

    ERIC Educational Resources Information Center

    Burgess, Jacquelin; Unwin, David

    1984-01-01

    In this interview David Attenborough, the celebrated natural history film maker and writer, talks about his highly successful television series, "The Living Planet." Devoted to the exposition of the world's ecosystems, the film represents a significant example of popular geographic education. (RM)

  12. David Ben-Gurion: A Creative Leader

    ERIC Educational Resources Information Center

    Rosemarin, Shoshana

    2014-01-01

    David Ben-Gurion (1886-1973), the first Prime Minister of Israel, is included in Pasternak's (2001) list of the nine most memorable leaders of the twentieth century. All of them are remembered for the reforms they initiated. Roosevelt (USA), Stalin (Russia), Castro (Cuba), and Thatcher (England) focused on social-economical changes, whereas Gandhi…

  13. David L. Gutmann (1925-2013).

    PubMed

    Rose, Jon; Huyck, Margaret; Grunes, Jerome

    2014-01-01

    David L. Gutmann, a pioneer in geropsychology and professor emeritus at Northwestern University, died on November 3, 2013, at the age of 88. A student of Bernice Neugarten, Bruno Bettelheim, and Erik Erikson, Gutmann discovered changes in adult psychological development related to parenting styles that held across diverse cultures.

  14. Speaking Personally--With David Foster

    ERIC Educational Resources Information Center

    American Journal of Distance Education, 2010

    2010-01-01

    David Foster is the founder of Kryterion, an Internet test administration company, and currently serves there as chief scientist and executive vice president. He is the author of numerous articles for industry trade journals and textbooks and sits on the Council for the International Test Commission. In this interview, Foster talks about his…

  15. Exploring the Living Planet with David Attenborough.

    ERIC Educational Resources Information Center

    Burgess, Jacquelin; Unwin, David

    1984-01-01

    In this interview David Attenborough, the celebrated natural history film maker and writer, talks about his highly successful television series, "The Living Planet." Devoted to the exposition of the world's ecosystems, the film represents a significant example of popular geographic education. (RM)

  16. Speaking Personally--With Mark David Milliron

    ERIC Educational Resources Information Center

    American Journal of Distance Education, 2008

    2008-01-01

    This article presents an interview with Mark David Milliron, board chair of the Institute for the Study of Knowledge Management in Education, a trustee with Western Governors University, and a member of the advisory board for the University of Texas (UT) TeleCampus. He is also president and CEO of Catalyze Learning International, a private…

  17. Interview with Dr. David H. Kalsbeek

    ERIC Educational Resources Information Center

    Sauter, David M.

    2005-01-01

    David H. Kalsbeek currently is vice president for enrollment management at DePaul University in Chicago, Illinois. In that capacity, he leads the marketing and enrollment development strategies for the nation's largest and fastest-growing Catholic university, enrolling 23,000 students in eight colleges and six campuses throughout the greater…

  18. Reading Pictures: An Interview with David Wiesner

    ERIC Educational Resources Information Center

    Varga-Dobai, Kinga

    2008-01-01

    Two-time Caldecott Honor winner (Free Fall, Sector 7) and three-time Caldecott Medal winner (Tuesday, The Three Pigs, Flotsam), David Wiesner is regarded as one of the most remarkable creators of visual storytelling living today. Wiesner is well known for his innovative and unique subject matter and his sophisticated painting-like illustrations…

  19. A Case of You: Remembering David Fowler

    ERIC Educational Resources Information Center

    Pimm, David

    2004-01-01

    The author has framed this brief appreciation of David Flower in terms of influence; specifically, his influence as a teacher, both in person and through his writing (most of all his attempted rewriting of much of the history of Greek mathematics). The author will also make some second-order remarks about the influence of teachers.

  20. An Interview with David Florio.

    ERIC Educational Resources Information Center

    Educational Evaluation and Policy Analysis, 1981

    1981-01-01

    American Educational Research Association's (AERA) lobbyist in Washington promotes educational research as a positive resource for educators. He acts to influence governmental policies which affect research. AERA represents a diversified membership by supporting a broad portfolio of government investments in educational research. AERA never takes…

  1. An Interview with David Florio.

    ERIC Educational Resources Information Center

    Educational Evaluation and Policy Analysis, 1981

    1981-01-01

    American Educational Research Association's (AERA) lobbyist in Washington promotes educational research as a positive resource for educators. He acts to influence governmental policies which affect research. AERA represents a diversified membership by supporting a broad portfolio of government investments in educational research. AERA never takes…

  2. Several Novel Nuclear Envelope Transmembrane Proteins Identified in Skeletal Muscle Have Cytoskeletal Associations*

    PubMed Central

    Wilkie, Gavin S.; Korfali, Nadia; Swanson, Selene K.; Malik, Poonam; Srsen, Vlastimil; Batrakou, Dzmitry G.; de las Heras, Jose; Zuleger, Nikolaj; Kerr, Alastair R. W.; Florens, Laurence; Schirmer, Eric C.

    2011-01-01

    Nuclear envelopes from liver and a neuroblastoma cell line have previously been analyzed by proteomics; however, most diseases associated with the nuclear envelope affect muscle. To determine whether muscle has unique nuclear envelope proteins, rat skeletal muscle nuclear envelopes were prepared and analyzed by multidimensional protein identification technology. Many novel muscle-specific proteins were identified that did not appear in previous nuclear envelope data sets. Nuclear envelope residence was confirmed for 11 of these by expression of fusion proteins and by antibody staining of muscle tissue cryosections. Moreover, transcript levels for several of the newly identified nuclear envelope transmembrane proteins increased during muscle differentiation using mouse and human in vitro model systems. Some of these proteins tracked with microtubules at the nuclear surface in interphase cells and accumulated at the base of the microtubule spindle in mitotic cells, suggesting they may associate with complexes that connect the nucleus to the cytoskeleton. The finding of tissue-specific proteins in the skeletal muscle nuclear envelope proteome argues the importance of analyzing nuclear envelopes from all tissues linked to disease and suggests that general investigation of tissue differences in organellar proteomes might yield critical insights. PMID:20876400

  3. 14. 1862 LITHOGRAPH SHOWING ST. DAVID'S CHURCH IN WINTER SCENE. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. 1862 LITHOGRAPH SHOWING ST. DAVID'S CHURCH IN WINTER SCENE. Photocopied from George Smith's book, History of Delaware County, Penna., 1862 - St. David's Church (Episcopal), Valley Forge Road (Newtown Township), Wayne, Delaware County, PA

  4. Some features of DNA fragments associated in vivo with the nuclear lamina

    SciTech Connect

    Christova, R.; Yaneva, J.; Galcheva-Gargova, Z. )

    1989-10-01

    Ehrlich Ascites Tumour cells were irradiated with UV-light to crosslink DNA to proteins in vivo. The DNA fragments associated with the nuclear lamina were purified and characterized. The results of the Cot analysis and the hybridization experiments suggest that the DNA fragments attached to the nuclear lamina although containing the entire complexity of genomic DNA are enriched in some highly repeated sequences.

  5. 77 FR 26765 - David H.M. Phelps: Debarment Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... HUMAN SERVICES Food and Drug Administration David H.M. Phelps: Debarment Order AGENCY: Food and Drug... under the Federal Food, Drug, and Cosmetic Act (FD&C Act) debarring David H.M. Phelps for a period of 20... Manual Guide 1410.35), finds that Mr. David H.M. Phelps has been convicted of 10 felony counts...

  6. Interface between astrophysical datasets and distributed database management systems (DAVID)

    NASA Technical Reports Server (NTRS)

    Iyengar, S. S.

    1988-01-01

    This is a status report on the progress of the DAVID (Distributed Access View Integrated Database Management System) project being carried out at Louisiana State University, Baton Rouge, Louisiana. The objective is to implement an interface between Astrophysical datasets and DAVID. Discussed are design details and implementation specifics between DAVID and astrophysical datasets.

  7. 76 FR 12971 - David E. Berman: Debarment Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-09

    ... HUMAN SERVICES Food and Drug Administration David E. Berman: Debarment Order AGENCY: Food and Drug... the Federal Food, Drug, and Cosmetic Act (the FD&C Act) debarring David E. Berman, MD, for 3 years... 1410.35), finds that David E. Berman has been convicted of a misdemeanor under Federal law for...

  8. Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

    PubMed Central

    Domingo-Domenech, J; Mellado, B; Ferrer, B; Truan, D; Codony-Servat, J; Sauleda, S; Alcover, J; Campo, E; Gascon, P; Rovira, A; Ross, J S; Fernández, P L; Albanell, J

    2005-01-01

    Nuclear factor (NF)-κB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-κB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-κB active state. Nuclear localisation of NF-κB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-κB was detected in 57 (66.3%) specimens, and nuclear NF-κB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-κB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-κB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P=0.02), Gleason score (P=0.03) and nuclear NF-κB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-κB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-κB is an independent prognostic factor of biochemical relapse in prostate cancer. PMID:16278667

  9. David Gill: clock maker to global astronomer

    NASA Astrophysics Data System (ADS)

    Haley, P. A.

    2014-04-01

    Reduction in the uncertainty of physical measurements underpinned many advances in solar and stellar parallax, the determination of longitude, geodesy, and the accurate mapping of the heavens using celestial photography in the late nineteenth century. A pioneer in these areas, who successfully made the transition from clock maker in Aberdeen to H.M. Astronomer at the Cape of Good Hope was David Gill (1843-1914); Sir David Gill, K.C.B. from 1900. This paper celebrates the first third of Gill's career in astronomy and geodesy up to the time he was made redundant from Dun Echt Observatory at the end of 1875. It highlights how his horological skills were applied to telescope design and also how his aspirations to become a global astronomer started. The paper is timed to coincide with Gill's centenary anniversary year - he died 24 January 1914.

  10. Investigating Gravity Anomalies Associated with Underground Nuclear Explosions

    NASA Astrophysics Data System (ADS)

    Rowe, C. A.; Miller, E.; Musa, D.; Schultz-Fellenz, E. S.; Sussman, A. J.; Swanson, E.

    2016-12-01

    Detection of subsurface effects from underground nuclear explosions (UNEs) is an important aspect of the overall characterization of a site and UNE signatures, which is central to the mission of the National Nuclear Security Admistration's Office of Proliferation Detection, Defense Nuclear Non-Prolifeation Research and Development, Underground Nuclear Explosion Signatures Experiment (UNESE). We are conducting an experiment at the Nevada National Security Site (NNSS) that includes the acquisition of ground-based gravity data to contribute to a multi-disciplinary characterization of two UNEs located on Pahute Mesa. For one of the UNEs, the working point for the detonation was in zeolitic ash-flow tuff 600 m below the surface. For the other UNE, the detonation working point was also at a depth 600m below the surface and was located in flow breccias and lavas. No evidence of chimney collapse has been manifested for either of these UNEs, hence a cavity may still in place and may produce a detectable gravity anomaly. Each of the gravity surveys consist of 150 sites which were precisely located using a Trimble 5700 GPS receiver for lateral precision of 2 cm and vertical control of 3 cm. The readings were arranged in radial lines from Surface Ground Zero (SGZ), with spacing 10-20 m near the center, and increasing intervals for the distal portions of the lines, which extended to as much as 200 m from SGZ. Gravity were collected using a LaCoste-Romberg model G gravity meter at one location and a Scintrex G-5 at the other. We present a preliminary look at the gravity data in conjunction with forward modeling of the anticipated anomaly given a suite of possible post-explosion cavity and chimney features.

  11. Astronaut David Scott - Sample - "Genesis Rock" - MSC

    NASA Image and Video Library

    1971-08-12

    S71-43477 (12 Aug. 1971) --- Astronaut David R. Scott, right, commander of the Apollo 15 mission, gets a close look at the sample referred to as "Genesis rock" in the Non-Sterile Nitrogen Processing Line (NNPL) in the Lunar Receiving Laboratory (LRL) at the Manned Spacecraft Center (MSC). Scientist-astronaut Joseph P. Allen IV, left, an Apollo 15 spacecraft communicator, looks on with interest. The white-colored rock has been given the permanent identification of 15415.

  12. A Bayesian network model of proteins' association with promyelocytic leukemia (PML) nuclear bodies.

    PubMed

    Bodén, Mikael; Dellaire, Graham; Burrage, Kevin; Bailey, Timothy L

    2010-04-01

    The modularity that nuclear organization brings has the potential to explain the function of aggregates of proteins and RNA. Promyelocytic leukemia nuclear bodies are implicated in important regulatory processes. To understand the complement of proteins associated with these intra-nuclear bodies, we construct a Bayesian network model that integrates sequence and protein-protein interaction data. The model predicts association with promyelocytic leukemia nuclear bodies accurately when interaction data is available. At a false positive rate of 10%, the true positive rate is almost 50%, indicated by an independent nuclear proteome reference set. The model provides strong support for further expanding the protein complement with several important regulators and a richer functional repertoire. Using special support vector machine (SVM)-nodes (equipped with string kernels), the Bayesian network is also able to produce predictions on the basis of sequence only, with an accuracy superior to that of baseline models. Supplementary Material is available online at www.liebertonline.com.

  13. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

    SciTech Connect

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M.; Heery, David M.

    2010-01-01

    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBP{Delta}998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.

  14. Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma.

    PubMed

    Liu, Shuli; Shi, Lei; Yang, Xi; Ye, Dongxia; Wang, Tong; Dong, Cunshan; Guo, Wenzheng; Liao, Yueling; Song, Hongyong; Xu, Dongliang; Hu, Jingzhou; Zhang, Zhiyuan; Deng, Jiong

    2017-04-06

    Defects in apoptotic pathway contribute to development and progression of oral cancer. Survivin, a member of the inhibitors of apoptosis protein (IAP) family, is increased in many types of cancers. However, it is unclear whether increased survivin is associated with oral squamous cell carcinomas (OSCC), and what mechanisms may involve in. In this study, we examined survivin expression in OSCC compared to normal oral tissues via immunohistochemical staining. The results showed that, not only total survivin is increased in OSCCs, but also the subcellular location of survivin is changed in OSCCs compared to normal oral tissues. In most of normal oral tissues, survivin staining was either negative, or cytoplasmic positive/nuclear negative; whereas in most of OSCC tissues, survivin staining was nuclear positive. Statistic analysis indicates that nuclear survivin, rather than total or cytoplasmic one, correlates with tumor TNM stage and differentiation grade. Consistently, in vitro analysis showed that survivin is in cytoplasm in normal human oral kinotinocyte (HOK) cells; whereas it is in nucleus in OSCC HN6 cells. Importantly, treatment of HOK cells with HDAC inhibitor Trichostatin A (TSA) induces survivin acetylation and promotes its nuclear localization. Moreover, nuclear survivin in OSCC cells was acetylated at K129 in its C-terminal, suggesting that the acetylation is important for nuclear location of survivin. Our study demonstrates that it is nuclear survivin, rather than total or cytoplasmic one, associates with TNM stage and tumor grade of OSCC. Thus, we propose nuclear survivin as a prognostic marker for the progression of OSCC.

  15. Nuclear power and nuclear weapons

    SciTech Connect

    Vaughen, V.C.A.

    1983-01-01

    The proliferation of nuclear weapons and the expanded use of nuclear energy for the production of electricity and other peaceful uses are compared. The difference in technologies associated with nuclear weapons and nuclear power plants are described.

  16. First Scholarship at AGU Established by David E. Lumley

    NASA Astrophysics Data System (ADS)

    Tahar, Joanna G.

    2009-09-01

    Shortly after AGU launched its annual voluntary contribution campaign last year—the theme was “Building Tomorrow's Talent Today”—the Union's development office received an e-mail message from David E. Lumley about establishing a scholarship for a high-school student or undergraduate. Many scientific societies and associations have quite a few named scholarships, but for AGU this was a new concept. Lumley was sure of what he wanted to do and even more excited when he learned that his scholarship would be a first for AGU. “I want to help inspire today's young minds to work on problems of global importance in both the energy and environment sectors of industry and academia,” Lumley said. Recipients of the David E. Lumley Young Scientist Scholarship for Energy and Environmental Science will be expected to present a paper and to participate in various student activities at Fall Meeting. “Meeting some of the ‘giants’ of geoscience and getting their feedback on research is a big deal for these young students. We sometimes lose sight of this,” he said.

  17. America's foremost early astronomer. [David Rittenhouse

    NASA Technical Reports Server (NTRS)

    Rubincam, David Parry; Rubincam, Milton, II

    1995-01-01

    The life of 18th century astronomer, craftsman, and partriot David Rittenhouse is detailed. As a craftsman, he distinguished himself as one of the foremost builders of clocks. He also built magnetic compasses and surveying instruments. The finest examples of his craftsmanship are considered two orreries, mechanical solar systems. In terms of astronomical observations, his best-known contribution was his observation of the transit of Venus in 1769. Rittenhouse constructed the first diffraction grating. Working as Treasurer of Pennsylvania throughout the Revolution, he became the first director of the Mint in 1792. Astronomical observations in later life included charting the position of Uranus after its discovery.

  18. America's foremost early astronomer. [David Rittenhouse

    NASA Technical Reports Server (NTRS)

    Rubincam, David Parry; Rubincam, Milton, II

    1995-01-01

    The life of 18th century astronomer, craftsman, and partriot David Rittenhouse is detailed. As a craftsman, he distinguished himself as one of the foremost builders of clocks. He also built magnetic compasses and surveying instruments. The finest examples of his craftsmanship are considered two orreries, mechanical solar systems. In terms of astronomical observations, his best-known contribution was his observation of the transit of Venus in 1769. Rittenhouse constructed the first diffraction grating. Working as Treasurer of Pennsylvania throughout the Revolution, he became the first director of the Mint in 1792. Astronomical observations in later life included charting the position of Uranus after its discovery.

  19. Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion.

    PubMed

    Krull, Sandra; Dörries, Julia; Boysen, Björn; Reidenbach, Sonja; Magnius, Lars; Norder, Helene; Thyberg, Johan; Cordes, Volker C

    2010-05-19

    Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution.

  20. Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion

    PubMed Central

    Krull, Sandra; Dörries, Julia; Boysen, Björn; Reidenbach, Sonja; Magnius, Lars; Norder, Helene; Thyberg, Johan; Cordes, Volker C

    2010-01-01

    Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution. PMID:20407419

  1. Computational image analysis of nuclear morphology associated with various nuclear-specific aging disorders.

    PubMed

    Choi, Siwon; Wang, Wei; Ribeiro, Alexandrew J S; Kalinowski, Agnieszka; Gregg, Siobhan Q; Opresko, Patricia L; Niedernhofer, Laura J; Rohde, Gustavo K; Dahl, Kris Noel

    2011-01-01

    Computational image analysis is used in many areas of biological and medical research, but advanced techniques including machine learning remain underutilized. Here, we used automated segmentation and shape analyses, with pre-defined features and with computer generated components, to compare nuclei from various premature aging disorders caused by alterations in nuclear proteins. We considered cells from patients with Hutchinson-Gilford progeria syndrome (HGPS) with an altered nucleoskeletal protein; a mouse model of XFE progeroid syndrome caused by a deficiency of ERCC1-XPF DNA repair nuclease; and patients with Werner syndrome (WS) lacking a functional WRN exonuclease and helicase protein. Using feature space analysis, including circularity, eccentricity, and solidity, we found that XFE nuclei were larger and significantly more elongated than control nuclei. HGPS nuclei were smaller and rounder than the control nuclei with features suggesting small bumps. WS nuclei did not show any significant shape changes from control. We also performed principle component analysis (PCA) and a geometric, contour based metric. PCA allowed direct visualization of morphological changes in diseased nuclei, whereas standard, feature-based approaches required pre-defined parameters and indirect interpretation of multiple parameters. Both methods yielded similar results, but PCA proves to be a powerful pre-analysis methodology for unknown systems.

  2. Kaposi's sarcoma-associated herpesvirus polyadenylated nuclear RNA: a structural scaffold for nuclear, cytoplasmic and viral proteins

    PubMed Central

    Rausch, Jason W.; Smith, Rodman; Miller, Jennifer T.; Whitby, Denise

    2017-01-01

    Abstract Kaposi's sarcoma-associated herpes virus (KSHV) polyadenylated nuclear (PAN) RNA facilitates lytic infection, modulating the cellular immune response by interacting with viral and cellular proteins and DNA. Although a number nucleoprotein interactions involving PAN have been implicated, our understanding of binding partners and PAN RNA binding motifs remains incomplete. Herein, we used SHAPE-mutational profiling (SHAPE-MaP) to probe PAN in its nuclear, cytoplasmic or viral environments or following cell/virion lysis and removal of proteins. We thus characterized and put into context discrete RNA structural elements, including the cis-acting Mta responsive element and expression and nuclear retention element (1,2). By comparing mutational profiles in different biological contexts, we identified sites on PAN either protected from chemical modification by protein binding or characterized by a loss of structure. While some protein binding sites were selectively localized, others were occupied in all three biological contexts. Individual binding sites of select KSHV gene products on PAN RNA were also identified in in vitro experiments. This work constitutes the most extensive structural characterization of a viral lncRNA and interactions with its protein partners in discrete biological contexts, providing a broad framework for understanding the roles of PAN RNA in KSHV infection. PMID:28383682

  3. Kaposi's sarcoma-associated herpesvirus polyadenylated nuclear RNA: a structural scaffold for nuclear, cytoplasmic and viral proteins.

    PubMed

    Sztuba-Solinska, Joanna; Rausch, Jason W; Smith, Rodman; Miller, Jennifer T; Whitby, Denise; Le Grice, Stuart F J

    2017-04-05

    Kaposi's sarcoma-associated herpes virus (KSHV) polyadenylated nuclear (PAN) RNA facilitates lytic infection, modulating the cellular immune response by interacting with viral and cellular proteins and DNA. Although a number nucleoprotein interactions involving PAN have been implicated, our understanding of binding partners and PAN RNA binding motifs remains incomplete. Herein, we used SHAPE-mutational profiling (SHAPE-MaP) to probe PAN in its nuclear, cytoplasmic or viral environments or following cell/virion lysis and removal of proteins. We thus characterized and put into context discrete RNA structural elements, including the cis-acting Mta responsive element and expression and nuclear retention element (1,2). By comparing mutational profiles in different biological contexts, we identified sites on PAN either protected from chemical modification by protein binding or characterized by a loss of structure. While some protein binding sites were selectively localized, others were occupied in all three biological contexts. Individual binding sites of select KSHV gene products on PAN RNA were also identified in in vitro experiments. This work constitutes the most extensive structural characterization of a viral lncRNA and interactions with its protein partners in discrete biological contexts, providing a broad framework for understanding the roles of PAN RNA in KSHV infection.

  4. Obituary: David Q. Wark, 1918-2002

    NASA Astrophysics Data System (ADS)

    McMillin, Larry Max

    2003-12-01

    the American Meteorological Society, the Lloyd V. Berkner Space Utilization Award from the American Astronautical Society, and the Robert M. Losey Award, from the American Institute of Aeronautics and Astronautics. David Quentin Wark was born on 25 March 1918, in Spokane, Washington. He was the fourth and last child of Percival Damon Wark and Clara Belle (née Mackey) Wark. In 1921 his family moved to Altadena and Pasadena, California, where he lived until 1939. He attended Altadena Elementary School, Edison Elementary School, Washington Junior High School, Pasadena High School, and Pasadena Junior College. From 1938 to 1939, and again in the summer of 1940, he worked for the Associated Press and David Lawrence to earn money to resume his education. In 1939, he entered the University of California, Berkeley, from which he graduated with a BA in Astronomy with honors in May 1941. From 1941 to 1942 he did graduate study in meteorology at the University of California, Los Angeles. He resumed graduate studies part time in 1948 at the University of California, Berkeley, while working full time at the U.S. Weather Bureau and graduated with a PhD in Astronomy in January 1959. He remembered those times as tough days driving back and forth to Berkeley and living in Half-Moon Bay. Dr. Wark's professional career began in 1942 at the U.S. Naval Observatory, where he served as a Naval Officer until 1946. He then went to work for the U.S. Weather Bureau. He spent the first three years of that period in Istres, France, Frankfurt and Munich, Germany, and Cairo Egypt. From 1949 through 1958 he served at the Aviation Weather Forecast Office in San Francisco. He then moved to the U.S. Weather Bureau Office in Suitland, Maryland, where he worked from November 1958 until 3 July 1999, when he officially retired. He actually retired from NOAA because during this time, he saw the U.S. Weather Bureau become part of ESSA which, in turn, became a part the National Oceanic and Atmospheric

  5. Nuclear Terms: a glossary

    SciTech Connect

    Freiwald, David A.

    1981-05-31

    This booklet is a revision of Nuclear Terms: A Glossary, published in 1967 by the United States Atomic Energy Commission. New fields, such as laser fusion and laser isotope separation, are included and nuclear weapons terms are deleted. Thus, it is a glossary for nuclear fission and fusion science and for commercial applications. David A. Freiwald, Frank C. DiLuzio, and Leslie M. Redman prepared this revised glossary. Contributions were made by other members of the Los Alamos National Laboratory staff.

  6. Reconstructing the Foreign Teacher: The Nativization of David Crook in Beijing

    ERIC Educational Resources Information Center

    Jacobsen, Craig K.

    2012-01-01

    This paper is a critical examination of the life and work of David Crook (1910-2000) as an English teacher in China from just prior to 1949 through the 1980's. It describes Crook's struggle to transcend attitudes of superiority commonly associated with native speaking English teachers at the time as well as his efforts to introduce innovations in…

  7. 2. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Historic American Buildings Survey, David Aronow, Photographer circa 1924, FRONT ELEVATION SHOWING BELLTOWER AND PROJECTING VERANDA. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  8. 3. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Historic American Buildings Survey, David Aronow, Photographer circa 1924, DETAIL OF FRONT ELEVATION SHOWING PROJECTING VERANDA. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  9. 13. SECOND FLOOR, CHILDREN'S LIBRARY, LUNETTE PAINTING 'INVENTION' BY DAVID ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. SECOND FLOOR, CHILDREN'S LIBRARY, LUNETTE PAINTING 'INVENTION' BY DAVID HUTCHINSON, WEST HALF, LOOKING WEST - Yonkers Public Library, Nepperhan Avenue & South Broadway, Yonkers, Westchester County, NY

  10. 14. SECOND FLOOR, CHILDREN'S LIBRARY, LUNETTE PAINTING 'INVENTION' BY DAVID ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. SECOND FLOOR, CHILDREN'S LIBRARY, LUNETTE PAINTING 'INVENTION' BY DAVID HUTCHINSON, NORTH HALF LOOKING NORTH - Yonkers Public Library, Nepperhan Avenue & South Broadway, Yonkers, Westchester County, NY

  11. David Lasser - An American Spaceflight Pioneer

    NASA Technical Reports Server (NTRS)

    Ciancone, Michael L.; Lasser, Amelia

    2002-01-01

    David Lasser was one of the founders of the American Interplanetary Society (later known as the American Rocket Society) and author of the first English-language book (in 1931) on the use of rockets for human spaceflight. His involvement in the fledgling spaceflight movement was short-lived as he moved on to pursue a distinguished, if turbulent, career in the labor movement. In lieu of an oral history, Mr. Lasser provided his recollections on the pioneering days of rocketry and his thoughts on mankind's destiny in space. This paper provides an overview of Mr. Lasser's life and accomplishments as an American spaceflight visionary, along with a compilation of the information that he graciously provided.

  12. David D. Derse, 1949-2009.

    PubMed

    Shuh, Maureen

    2009-12-01

    David D. Derse, Ph.D., Head of the Retrovirus Gene Expression Section in the HIV Drug Resistance Program at the National Cancer Institute-Frederick (NCI-Frederick), passed away on October 9, 2009, a scant six weeks after being diagnosed with liver cancer. It was with great sadness that family, friends, and colleagues gathered together for his memorial service on Saturday, October 17, 2009, at the Middletown United Methodist Church in Maryland. As a NCI scientist since 1986, Dave studied the molecular mechanisms of infection and replication of a number of different types of retroviruses. Dave became an internationally known expert on human T cell lymphotrophic viruses type 1 and 2 (HTLV-1 and HTLV-2) and served on the editorial boards of Virology and Retrovirology. His most recent studies focused on the mechanisms of HTLV-1 virion morphogenesis, transmission, and replication.

  13. Rainforest pioneer. Millennium trailblazers 3: David Cassell.

    PubMed

    Gilmour, D

    1999-01-01

    The Iwokrama International Centre for Rain Forest Conservation in Guyana is headed by Australian forester David Cassells who is also chairman of the Advisory Group for the World Conservation Union Forest Conservation Program. He states that this program is different from other projects to conserve tropical forests since it focuses on financial sustainability and self-sufficiency. He also plans that the revenue for the center will come from a mixture of eco-forestry with certified logging, ecotourism, sustainable production of non-timber products such as vines and latexes, bioprospecting, and the sale of forest management expertise. He further added that the program's success could change the way people value and use tropical forests.

  14. The Alarmin Properties of DNA and DNA-associated Nuclear Proteins.

    PubMed

    Magna, Melinda; Pisetsky, David S

    2016-05-01

    The communication of cell injury and death is a critical element in host defense. Although immune cells can serve this function by elaborating cytokines and chemokines, somatic cells can repurpose nuclear macromolecules to function as damage-associated molecular patterns (DAMPs) or alarmins to exert similar activity. Among these molecules, DNA, high-mobility group box-1, and histone proteins can all act as DAMPs once they are in an extracellular location. This review describes current information on the role of the nuclear DAMPs, their translocation to the outside of cells, and pathways of activation after uptake into the inside of immune cells. MEDLINE and PubMed databases were searched for citations (1990-2016) in English related to the following terms: DAMPs, high-mobility group box-1, DNA, histones, cell death, danger, and immune activation. Selected articles with the most relevant studies were included for a more detailed consideration. Although nuclear molecules have important structural and genetic regulatory roles inside the cell nucleus, when released into the extracellular space during cell death, these molecules can acquire immune activity and serve as alarmins or DAMPs. Although apoptosis is generally considered the source of extracellular nuclear material, other cell death pathways such as necroptosis, NETosis, and pyroptosis can contribute to the release of nuclear molecules. Importantly, the release of nuclear DAMPs occurs with both soluble and particulate forms of these molecules. The activity of nuclear molecules may depend on posttranslational modifications, redox changes, and the binding of other molecules. Once in an extracellular location, nuclear DAMPs can engage the same pattern recognition receptors as do pathogen-associated molecular patterns. These interactions can activate immune cells and lead to cytokine and chemokine production. Among these receptors, internal receptors for DNA are key to the response to this molecule; the likely

  15. Recombinant adeno-associated virus utilizes host cell nuclear import machinery to enter the nucleus.

    PubMed

    Nicolson, Sarah C; Samulski, R Jude

    2014-04-01

    Recombinant adeno-associated viral (rAAV) vectors have garnered much promise in gene therapy applications. However, widespread clinical use has been limited by transduction efficiency. Previous studies suggested that the majority of rAAV accumulates in the perinuclear region of cells, presumably unable to traffic into the nucleus. rAAV nuclear translocation remains ill-defined; therefore, we performed microscopy, genetic, and biochemical analyses in vitro in order to understand this mechanism. Lectin blockade of the nuclear pore complex (NPC) resulted in inhibition of nuclear rAAV2. Visualization of fluorescently labeled particles revealed that rAAV2 localized to importin-β-dense regions of cells in late trafficking steps. Additionally, small interfering RNA (siRNA) knockdown of importin-β partially inhibited rAAV2 nuclear translocation and inhibited transduction by 50 to 70%. Furthermore, coimmunopreciptation (co-IP) analysis revealed that capsid proteins from rAAV2 could interact with importin-β and that this interaction was sensitive to the small GTPase Ran. More importantly, mutations to key basic regions in the rAAV2 capsid severely inhibited interactions with importin-β. We tested several other serotypes and found that the extent of importin-β interaction varied, suggesting that different serotypes may utilize alternative import proteins for nuclear translocation. Co-IP and siRNA analyses were used to investigate the role of other karyopherins, and the results suggested that rAAV2 may utilize multiple import proteins for nuclear entry. Taken together, our results suggest that rAAV2 interacts with importin-β alone or in complex with other karyopherins and enters the nucleus via the NPC. These results may lend insight into the design of novel AAV vectors that have an enhanced nuclear entry capability and transduction potential. Use of recombinant adeno-associated viral (rAAV) vectors for gene therapy applications is limited by relatively low transduction

  16. David Lukens Reasoner (1941-1992)

    NASA Astrophysics Data System (ADS)

    Chappell, Rick

    David Lukens Reasoner, former head of NASA's Ionospheric Physics branch, died on April 21, 1992. Reasoner was born July 1, 1941. He worked tirelessly to expand NASA's Space Physics Division, bringing his deep experience and personal expertise to bear on the challenges of growth.During the magical period of the late 1950s and early 1960s when America turned its eyes toward space and the Moon, David Lukens Reasoner journeyed north from the nearby Texas town of Dickinson to Rice University with an idea of getting involved in exploring the frontiers of space. He pursued a course of study in electrical engineering and received a bachelor's degree in 1963 and a master's degree in 1964. In the early 1960s, the Space Science Department at Rice was formed, and President John Kennedy visited to say that America chose to go to space not because it is easy but because it is hard and because it would require the very best talents of our nation to succeed. Dave Reasoner was one of those talented people. His excellence in electrical engineering and physics, combined with his natural abilities in the laboratory, suited him ideally for building the machines of space. As a student, he built sounding rocket payloads and multiple instruments for satellites and experiment packages that were placed on the Moon by the Apollo astronauts. He completed his doctoral degree in space science in 1968. It was in these early thrilling days of space exploration that I first met Dave, beginning a friendship and collegial relationship that was to last 27 years.

  17. Nuclear localization of the dystrophin-associated protein α-dystrobrevin through importin α2/β1 is critical for interaction with the nuclear lamina/maintenance of nuclear integrity.

    PubMed

    Aguilar, Areli; Wagstaff, Kylie M; Suárez-Sánchez, Rocío; Zinker, Samuel; Jans, David A; Cisneros, Bulmaro

    2015-05-01

    Although α-dystrobrevin (DB) is assembled into the dystrophin-associated protein complex, which is central to cytoskeletal organization, it has also been found in the nucleus. Here we delineate the nuclear import pathway responsible for nuclear targeting of α-DB for the first time, together with the importance of nuclear α-DB in determining nuclear morphology. We map key residues of the nuclear localization signal of α-DB within the zinc finger domain (ZZ) using various truncated versions of the protein, and site-directed mutagenesis. Pulldown, immunoprecipitation, and AlphaScreen assays showed that the importin (IMP) α2/β1 heterodimer interacts with high affinity with the ZZ domain of α-DB. In vitro nuclear import assays using antibodies to specific importins, as well as in vivo studies using siRNA or a dominant negative importin construct, confirmed the key role of IMPα2/β1 in α-DB nuclear translocation. Knockdown of α-DB expression perturbed cell cycle progression in C2C12 myoblasts, with decreased accumulation of cells in S phase and, significantly, altered localization of lamins A/C, B1, and B2 with accompanying gross nuclear morphology defects. Because α-DB interacts specifically with lamin B1 in vivo and in vitro, nuclear α-DB would appear to play a key role in nuclear shape maintenance through association with the nuclear lamina.

  18. Third Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Third Annual David Derse Memorial Lecture and Award presentation was held on Nov. 18 at NCI at Frederick to honor the outstanding research accomplishments of David Derse, Ph.D., and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career.

  19. Third Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Third Annual David Derse Memorial Lecture and Award presentation was held on Nov. 18 at NCI at Frederick to honor the outstanding research accomplishments of David Derse, Ph.D., and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career.

  20. 75 FR 10244 - Ellsworth, David C.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ... [Federal Register Volume 75, Number 43 (Friday, March 5, 2010)] [Notices] [Page 10244] [FR Doc No: 2010-4611] DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ID-3716-001] Ellsworth, David C.; Notice of Filing February 25, 2010. Take notice that on February 12, 2010, David C....

  1. 77 FR 71189 - Falck, David P.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... Energy Regulatory Commission Falck, David P.; Notice of Filing Take notice that on November 23, 2012, David P. Falck submitted for filing, an application for authority to hold interlocking positions...-8659. Comment Date: 5:00 p.m. Eastern Time on December 14, 2012. Dated: November 23, 2012. Kimberly...

  2. Teaching Students about the Environment with Henry David Thoreau

    ERIC Educational Resources Information Center

    Curriculum Review, 2008

    2008-01-01

    "Walden: The Ballad of Thoreau" is a two-act four-character play about the final two days writer Henry David Thoreau spent in his cabin before leaving Walden Pond. Teachers can use this play to teach about preserving the earth to students. This article presents a brief synopsis of the play and a brief biography of Henry David Thoreau.

  3. Music: Part of the Basics at David Douglas and Salem.

    ERIC Educational Resources Information Center

    Pheasant, Marilyn

    1985-01-01

    This bulletin highlights elements of the music programs in two Oregon school districts--David Douglas School District 40 and Salem School District 24J--that have kept these programs viable in spite of financial constraints. Ingredients for success of the overall music program at David Douglas are first described. Important elements include hiring…

  4. Teaching Students about the Environment with Henry David Thoreau

    ERIC Educational Resources Information Center

    Curriculum Review, 2008

    2008-01-01

    "Walden: The Ballad of Thoreau" is a two-act four-character play about the final two days writer Henry David Thoreau spent in his cabin before leaving Walden Pond. Teachers can use this play to teach about preserving the earth to students. This article presents a brief synopsis of the play and a brief biography of Henry David Thoreau.

  5. A-type Lamins Form Distinct Filamentous Networks with Differential Nuclear Pore Complex Associations.

    PubMed

    Xie, Wei; Chojnowski, Alexandre; Boudier, Thomas; Lim, John S Y; Ahmed, Sohail; Ser, Zheng; Stewart, Colin; Burke, Brian

    2016-10-10

    The nuclear lamina is a universal feature of metazoan nuclear envelopes (NEs) [1]. In mammalian cells, it appears as a 10-30 nm filamentous layer at the nuclear face of the inner nuclear membrane (INM) and is composed primarily of A- and B-type lamins, members of the intermediate filament family [2]. While providing structural integrity to the NE, the lamina also represents an important signaling and regulatory platform [3]. Two A-type lamin isoforms, lamins A and C (LaA and LaC), are expressed in most adult human cells. Encoded by a single gene, these proteins are largely identical, diverging only in their C-terminal tail domains. By contrast with that of LaC, the unique LaA tail undergoes extensive processing, including farnesylation and endo-proteolysis [4, 5]. However, functional differences between LaA and LaC are still unclear. Compounding this uncertainty, the structure of the lamina remains ill defined. In this study, we used BioID, an in vivo proximity-labeling method to identify differential interactors of A-type lamins [6]. One of these, Tpr, a nuclear pore complex (NPC) protein, is highlighted by its selective association with LaC. By employing superresolution microscopy, we demonstrate that this Tpr association is mirrored in enhanced interaction of LaC with NPCs. Further superresolution studies visualizing both endogenous A- and B-type lamins have allowed us to construct a nanometer-scale model of the mammalian nuclear lamina. Our data indicate that different A- and B-type lamin species assemble into separate filament networks that together form an extended composite structure at the nuclear periphery providing attachment sites for NPCs, thereby regulating their distribution.

  6. Nuclear γ-tubulin associates with nucleoli and interacts with tumor suppressor protein C53.

    PubMed

    Hořejší, Barbora; Vinopal, Stanislav; Sládková, Vladimíra; Dráberová, Eduarda; Sulimenko, Vadym; Sulimenko, Tetyana; Vosecká, Věra; Philimonenko, Anatoly; Hozák, Pavel; Katsetos, Christos D; Dráber, Pavel

    2012-01-01

    γ-Tubulin is assumed to be a typical cytosolic protein necessary for nucleation of microtubules from microtubule organizing centers. Using immunolocalization and cell fractionation techniques in combination with siRNAi and expression of FLAG-tagged constructs, we have obtained evidence that γ-tubulin is also present in nucleoli of mammalian interphase cells of diverse cellular origins. Immunoelectron microscopy has revealed γ-tubulin localization outside fibrillar centers where transcription of ribosomal DNA takes place. γ-Tubulin was associated with nucleolar remnants after nuclear envelope breakdown and could be translocated to nucleoli during mitosis. Pretreatment of cells with leptomycin B did not affect the distribution of nuclear γ-tubulin, making it unlikely that rapid active transport via nuclear pores participates in the transport of γ-tubulin into the nucleus. This finding was confirmed by heterokaryon assay and time-lapse imaging of photoconvertible protein Dendra2 tagged to γ-tubulin. Immunoprecipitation from nuclear extracts combined with mass spectrometry revealed an association of γ-tubulin with tumor suppressor protein C53 located at multiple subcellular compartments including nucleoli. The notion of an interaction between γ-tubulin and C53 was corroborated by pull-down and co-immunoprecipitation experiments. Overexpression of γ-tubulin antagonized the inhibitory effect of C53 on DNA damage G(2) /M checkpoint activation. The combined results indicate that aside from its known role in microtubule nucleation, γ-tubulin may also have nuclear-specific function(s).

  7. DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis.

    PubMed

    Sherman, Brad T; Huang, Da Wei; Tan, Qina; Guo, Yongjian; Bour, Stephan; Liu, David; Stephens, Robert; Baseler, Michael W; Lane, H Clifford; Lempicki, Richard A

    2007-11-02

    Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/.

  8. The MUC1 Extracellular Domain Subunit Is Found in Nuclear Speckles and Associates with Spliceosomes

    PubMed Central

    Kumar, Priyadarsina; Ji, Jennifer W.; Martsching, Lindsay; Douglas, Gordon C.

    2012-01-01

    MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C) can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N) does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity ligation assay, subcellular fractionation, and immunoprecipitation suggests that MUC1-N is located in nuclear speckles (interchromatin granule clusters) and closely associates with the spliceosome protein U2AF65. Nuclear localization of MUC1-N was abolished when cells were treated with RNase A and nuclear localization was altered when cells were incubated with the transcription inhibitor 5,6-dichloro-1-b-d-ribofuranosylbenzimidazole (DRB). While MUC1-N predominantly associated with speckles, MUC1-C was present in the nuclear matrix, nucleoli, and the nuclear periphery. In some nuclei, confocal microscopic analysis suggest that MUC1-C staining is located close to, but only partially overlaps, MUC1-N in speckles. However, only MUC1-N was found in isolated speckles by Western blotting. Also, MUC1-C and MUC1-N distributed differently during mitosis. These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC1-C have

  9. Nuclear lamins are not required for lamina-associated domain organization in mouse embryonic stem cells

    PubMed Central

    Amendola, Mario; van Steensel, Bas

    2015-01-01

    In mammals, the nuclear lamina interacts with hundreds of large genomic regions, termed lamina-associated domains (LADs) that are generally in a transcriptionally repressed state. Lamins form the major structural component of the lamina and have been reported to bind DNA and chromatin. Here, we systematically evaluate whether lamins are necessary for the LAD organization in murine embryonic stem cells. Surprisingly, removal of essentially all lamins does not have any detectable effect on the genome-wide interaction pattern of chromatin with emerin, a marker of the inner nuclear membrane. This suggests that other components of the lamina mediate these interactions. PMID:25784758

  10. Obituary: David L. Band (1957-2009)

    NASA Astrophysics Data System (ADS)

    Cominsky, Lynn

    2011-12-01

    David L. Band, of Potomac Maryland, died on March 16, 2009 succumbing to a long battle with spinal cord cancer. His death at the age of 52 came as a shock to his many friends and colleagues in the physics and astronomy community. Band showed an early interest and exceptional aptitude for physics, leading to his acceptance at the Massachusetts Institute of Technology as an undergraduate student in 1975. After graduating from MIT with an undergraduate degree in Physics, Band continued as a graduate student in Physics at Harvard University. His emerging interest in Astrophysics led him to the Astronomy Department at the Harvard Smithsonian Center for Astrophysics (CfA), where he did his dissertation work with Jonathan Grindlay. His dissertation (1985) entitled "Non-thermal Radiation Mechanisms and Processes in SS433 and Active Galactic Nuclei" was "pioneering work on the physics of jets arising from black holes and models for their emission, including self-absorption, which previewed much to come, and even David's own later work on Gamma-ray Bursts," according to Grindlay who remained a personal friend and colleague of Band's. Following graduate school, Band held postdoctoral positions at the Lawrence Livermore Laboratory, the University of California at Berkeley and the Center for Astronomy and Space Sciences at the University of California San Diego where he worked on the BATSE experiment that was part of the Compton Gamma Ray Observatory (CGRO), launched in 1991. BATSE had as its main objective the study of cosmic gamma-ray bursts (GRBs) and made significant advances in this area of research. Band became a world-renowned figure in the emerging field of GRB studies. He is best known for his widely-used analytic form of gamma-ray burst spectra known as the "Band Function." After the CGRO mission ended, Band moved to the Los Alamos National Laboratory where he worked mainly on classified research but continued to work on GRB energetics and spectra. When NASA planned

  11. The David and Goliath principle: cultural, ideological, and attitudinal underpinnings of the normative protection of low-status groups from criticism.

    PubMed

    Jeffries, Carla H; Hornsey, Matthew J; Sutton, Robbie M; Douglas, Karen M; Bain, Paul G

    2012-08-01

    Two studies documented the "David and Goliath" rule--the tendency for people to perceive criticism of "David" groups (groups with low power and status) as less normatively permissible than criticism of "Goliath" groups (groups with high power and status). The authors confirmed the existence of the David and Goliath rule across Western and Chinese cultures (Study 1). However, the rule was endorsed more strongly in Western than in Chinese cultures, an effect mediated by cultural differences in power distance. Study 2 identified the psychological underpinnings of this rule in an Australian sample. Lower social dominance orientation (SDO) was associated with greater endorsement of the rule, an effect mediated through the differential attribution of stereotypes. Specifically, those low in SDO were more likely to attribute traits of warmth and incompetence to David versus Goliath groups, a pattern of stereotypes that was related to the protection of David groups from criticism.

  12. p63 Transcription Factor Regulates Nuclear Shape and Expression of Nuclear Envelope-Associated Genes in Epidermal Keratinocytes.

    PubMed

    Rapisarda, Valentina; Malashchuk, Igor; Asamaowei, Inemo E; Poterlowicz, Krzysztof; Fessing, Michael Y; Sharov, Andrey A; Karakesisoglou, Iakowos; Botchkarev, Vladimir A; Mardaryev, Andrei

    2017-10-01

    The maintenance of a proper nuclear architecture and three-dimensional organization of the genes, enhancer elements, and transcription machinery plays an essential role in tissue development and regeneration. Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets. Alterations in the nuclei shape and expression of nuclear envelope-associated proteins were accompanied by altered distribution patterns of the repressive histone marks trimethylation on lysine 27 of histone H3, trimethylation on lysine 9 of histone H3, and heterochromatin protein 1-alpha in p63-null keratinocytes. These changes were also accompanied by downregulation of the transcriptional activity and relocation of the keratinocyte-specific gene loci away from the sites of active transcription toward the heterochromatin-enriched repressive nuclear compartments in p63-null cells. These data demonstrate functional links between the nuclear envelope organization, chromatin architecture, and gene expression in keratinocytes and suggest nuclear envelope-associated genes as important targets mediating p63-regulated gene expression program in the epidermis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Nuclear actin is partially associated with Cajal bodies in human cells in culture and relocates to the nuclear periphery after infection of cells by adenovirus 5.

    PubMed

    Gedge, L J E; Morrison, E E; Blair, G E; Walker, J H

    2005-02-15

    Cajal bodies are intra-nuclear structures enriched in proteins involved in transcription and mRNA processing. In this study, immunofluorescence microscopy experiments using a highly specific antibody to actin revealed nuclear actin spots that colocalized in part with p80 coilin-positive Cajal bodies. Actin remained associated with Cajal bodies in cells extracted to reveal the nuclear matrix. Adenovirus infection, which is known to disassemble Cajal bodies, resulted in loss of actin from these structures late in infection. In infected cells, nuclear actin was observed to relocate to structures at the periphery of the nucleus, inside the nuclear envelope. Based on these findings, it is suggested that actin may play an important role in the organization or function of the Cajal body.

  14. The JIM interview. David Korn, MD.

    PubMed

    Korn, D

    1995-04-01

    When David Korn, MD, was named dean of the Stanford University School of Medicine on October 9, 1984, he assumed leadership of a world class research institution. Stanford was at the forefront of medicine in the areas of transplantation and oncology, and the steady influx of privately insured patients had generated a net operating surplus of $17 million in that year alone. However, in the same issue of the Stanford University Hospital newsletter which announced the selection of Korn as Dean, a small article appeared on a new prospective payment system based on diagnosis-related groups (DRGs). The article stated that the new system had begun smoothly, though some payments for cost outliers had been delayed. Other cost containment measures soon followed, most notably the implementation of managed care, and by 1990, Stanford was $14 million in the red. Buffeted by changes in medical reimbursement, competition with less costly hospitals, and a nasty squabble with Congress over indirect research costs, Stanford has been on the frontlines of a struggle now confronting many academic medical centers. After successfully consolidating the university's clinical services into a unified Stanford Health System, Korn announced that he would be stepping down as Dean on April 1. Interviewed in his office in Palo Alto, Korn reflected on the difficulties of dealing with managed care, the current financial state of the institution, and what Stanford's experience may predict for other academic medical centers.

  15. David J. Hofmann (1937-2009)

    NASA Astrophysics Data System (ADS)

    Deshler, Terry; Butler, James H.; Solomon, Susan; Barnes, John E.; Schnell, Russell C.

    2009-12-01

    David J. Hofmann, a pioneer in stratospheric aerosol and ozone research, passed away in Boulder, Colo., on 11 August 2009. He was 72. Dave, a frequent contributor to AGU publications and meetings, was elected an AGU Fellow in 2006. His long and prolific scientific career was, as he would say, simple in concept: Make a long-term commitment to specific measurements, pay attention to the details, and focus on the important issues that the measurements raise. This is simple in concept yet challenging to maintain in a world of short-term contracts and budgets. That Dave sustained and led key measurement programs through 25 years at the University of Wyoming (UW), in Laramie, and 17 years with the U.S. National Oceanic and Atmospheric Administration's (NOAA) Climate Monitoring and Diagnostics Laboratory (CMDL, which became the Global Monitoring Division (GMD) of NOAA's Earth System Research Laboratory) in Boulder, speaks volumes about the scientific and societal benefits that have resulted from his work. Most of the measurement programs he initiated, and the instruments he helped develop for them, continue today as testament to the value of his focus and lasting influence.

  16. David MacKay's wooden blocks

    NASA Astrophysics Data System (ADS)

    Skilling, John

    2017-06-01

    This paper is dedicated to the memory of Professor Sir David MacKay FRS. In his inspiring last talk, MacKay discussed the problem of packing his young son's identical wooden blocks, of size 2×1×1. How many ways are there of packing n3/2 such blocks into a cubical box of volume n3? This is the same problem as finding the entropy of cubic packing of dimeric molecules, so the investigation is not merely childish. Here, I use this example as an exemplar of the use of nested sampling in computational inference. In this analogy, the posterior covers the "glassy" arrangements of non-overlapping blocks in the box, whereas the prior represents the wider set of unrestricted model configurations. The required number of possible glass states is the compressive prior-to-posterior fraction of the known number of model configurations. And the compression (as logarithm) is immediately available from the number of equilibrating iterations in nested sampling. The clarity of this example offers useful lessons for computational inference more generally.

  17. Nuclear transfer: preservation of a nuclear genome at the expense of its associated mtDNA genome(s).

    PubMed

    Bowles, Emma J; Campbell, Keith H S; St John, Justin C

    2007-01-01

    Nuclear transfer technology has uses across theoretical and applied applications, but advances are restricted by continued poor success rates and health problems associated with live offspring. Development of reconstructed embryos is dependent upon numerous interlinking factors relating both to the donor cell and the recipient oocyte. For example, abnormalities in gene expression following somatic cell nuclear transfer (SCNT) have been linked with an inability of the oocyte cytoplasm to sufficiently epigenetically reprogram the nucleus. Furthermore, influences on the propagation of mitochondria and mitochondrial DNA (mtDNA) could be of great importance in determining the early developmental potential of NT embryos and contributing to their genetic identity. mtDNA encodes some of the subunits of the electron transfer chain, responsible for cellular ATP production. The remaining subunits and those factors required for mtDNA replication, transcription and translation are encoded by the nucleus, necessitating precise intergenomic communication. Additionally, regulation of mtDNA copy number, via the processes of mtDNA transcription and replication, is essential for normal preimplantation embryo development and differentiation. Unimaternal transmission following natural fertilization usually results in the presence of a single identical population of mtDNA, homoplasmy. Heteroplasmy can result if mixed populations of mtDNA genomes co-exist. Many abnormalities observed in NT embryos, fetuses, and offspring may be caused by deficiencies in OXPHOS, perhaps resulting in part from heteroplasmic mtDNA populations. Additionally, incompatibilities between the somatic nucleus and the cytoplast may be exacerbated by increased genetic divergence between the two genomes. It is important to ensure that the nucleus is capable of sufficiently regulating mtDNA, requiring a level of compatibility between the two genomes, which may be a function of evolutionary distance. We suggest that

  18. NUCLEAR MATERIAL ATTRACTIVENESS: AN ASSESSMENT OF MATERIAL ASSOCIATED WITH A CLOSED FUEL CYCLE

    SciTech Connect

    Bathke, C. G.; Ebbinghaus, B.; Sleaford, Brad W.; Wallace, R. K.; Collins, Brian A.; Hase, Kevin R.; Robel, Martin; Jarvinen, G. D.; Bradley, Keith S.; Ireland, J. R.; Johnson, M. W.; Prichard, Andrew W.; Smith, Brian W.

    2010-06-11

    This paper examines the attractiveness of materials mixtures containing special nuclear materials (SNM) associated with the various processing steps required for a closed fuel cycle. This paper combines the results from earlier studies that examined the attractiveness of SNM associated with the processing of spent light water reactor (LWR) fuel by various reprocessing schemes and the recycle of plutonium as a mixed oxide (MOX) fuel in LWR with new results for the final, repeated burning of SNM in fast-spectrum reactors: fast reactors and accelerator driven systems (ADS). The results of this paper suggest that all reprocessing products evaluated so far need to be rigorously safeguarded and provided moderate to high levels of physical protection. These studies were performed at the request of the United States Department of Energy (DOE), and are based on the calculation of "attractiveness levels" that has been couched in terms chosen for consistency with those normally used for nuclear materials in DOE nuclear facilities. The methodology and key findings will be presented. Additionally, how these attractiveness levels relate to proliferation resistance (e.g. by increasing impediments to the diversion, theft, or undeclared production of SNM for the purpose of acquiring a nuclear weapon), and how they could be used to help inform policy makers, will be discussed.

  19. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype.

    PubMed

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis.

  20. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype

    PubMed Central

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis. PMID:27031510

  1. Second Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Second Annual David Derse Memorial Lecture and Award presentation was held on November 12, 2013, at the NCI at Frederick Conference Center to honor David Derse’s outstanding research accomplishments and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career. The Annual David Derse Memorial Lecture and Award is sponsored by the HIV Drug Resistance Program, with support from Hye Kyung Chung-Derse, Ph.D., the National Cancer Institute (NCI), the Foundation for the National Institutes of Health (NIH), and colleagues and friends of Derse who contributed to the memorial fund in his honor.

  2. Second Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Second Annual David Derse Memorial Lecture and Award presentation was held on November 12, 2013, at the NCI at Frederick Conference Center to honor David Derse’s outstanding research accomplishments and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career. The Annual David Derse Memorial Lecture and Award is sponsored by the HIV Drug Resistance Program, with support from Hye Kyung Chung-Derse, Ph.D., the National Cancer Institute (NCI), the Foundation for the National Institutes of Health (NIH), and colleagues and friends of Derse who contributed to the memorial fund in his honor.

  3. A photographic diary of travels with David Kupfer.

    PubMed

    Estabrook, Ronald W

    2006-01-01

    The present article focuses on David Kupfer as a colleague and fellow traveler who participated in numerous meetings on cytochrome P450 held at exotic venues. It was always a pleasure to renew a long-standing friendship with David by meeting him at these meetings. His inscrutable smile combined with residues of an accent derived from his earlier background in Poland and Israel characterized this warm and delightful man. A number of photos of David in various locales are presented with this article in an attempt to fully capture the outstanding qualities of this man.

  4. Boundaries and interfaces in materials: The David A. Smith symposium

    SciTech Connect

    Pond, R.C. . Dept. of Materials Science and Engineering); Clark, W.A.T. . Dept. of Materials Science and Engineering); King, A.H. . Dept. of Materials Science and Engineering); Williams, D.B. (Lehigh Univ., Bethlehem, PA (United States

    1998-01-01

    Just over a year ago David Smith died. Then the loss of a distinguished scientist and dedicated teacher was mourned. Now it is time to celebrate his accomplishments both as a scientist and teacher and this book serves as a reminder of his many contributions to the field of boundaries and interfaces. Researchers from ten countries contributed their work to the symposium, many of whom were former students of David from his years in Oxford. This emphasizes David's tremendous effect on the career of many established scientists through his role as both a teacher and an advisor. Separate abstracts were prepared for 38 papers in this book.

  5. ENVIRONMENTAL PROBLEMS ASSOCIATED WITH DECOMMISSIONING THE CHERNOBYL NUCLEAR POWER PLANT COOLING POND

    SciTech Connect

    Farfan, E.

    2009-09-30

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities has been an imperative issue lately. There exist significant experience and generally accepted recommendations on remediation of lands with residual radioactive contamination; however, there are hardly any such recommendations on remediation of cooling ponds that, in most cases, are fairly large water reservoirs. The literature only describes remediation of minor reservoirs containing radioactive silt (a complete closure followed by preservation) or small water reservoirs resulting in reestablishing natural water flows. Problems associated with remediation of river reservoirs resulting in flooding of vast agricultural areas also have been described. In addition, the severity of environmental and economic problems related to the remedial activities is shown to exceed any potential benefits of these activities. One of the large, highly contaminated water reservoirs that require either remediation or closure is Karachay Lake near the MAYAK Production Association in the Chelyabinsk Region of Russia where liquid radioactive waste had been deep well injected for a long period of time. Backfilling of Karachay Lake is currently in progress. It should be noted that secondary environmental problems associated with its closure are considered to be of less importance since sustaining Karachay Lake would have presented a much higher radiological risk. Another well-known highly contaminated water reservoir is the Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond, decommissioning of which is planned for the near future. This study summarizes the environmental problems associated with the ChNPP Cooling Pond decommissioning.

  6. Environmental Problems Associated With Decommissioning The Chernobyl Nuclear Power Plant Cooling Pond

    SciTech Connect

    Farfan, E. B.; Jannik, G. T.; Marra, J. C.; Oskolkov, B. Ya.; Bondarkov, M. D.; Gaschak, S. P.; Maksymenko, A. M.; Maksymenko, V. M.; Martynenko, V. I.

    2009-11-09

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities has been an imperative issue lately. There exist significant experience and generally accepted recommendations on remediation of lands with residual radioactive contamination; however, there are hardly any such recommendations on remediation of cooling ponds that, in most cases, are fairly large water reservoirs. The literature only describes remediation of minor reservoirs containing radioactive silt (a complete closure followed by preservation) or small water reservoirs resulting in reestablishing natural water flows. Problems associated with remediation of river reservoirs resulting in flooding of vast agricultural areas also have been described. In addition, the severity of environmental and economic problems related to the remedial activities is shown to exceed any potential benefits of these activities. One of the large, highly contaminated water reservoirs that require either remediation or closure is Karachay Lake near the MAYAK Production Association in the Chelyabinsk Region of Russia where liquid radioactive waste had been deep well injected for a long period of time. Backfilling of Karachay Lake is currently in progress. It should be noted that secondary environmental problems associated with its closure are considered to be of less importance since sustaining Karachay Lake would have presented a much higher radiological risk. Another well-known highly contaminated water reservoir is the Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond, decommissioning of which is planned for the near future. This study summarizes the environmental problems associated with the ChNPP Cooling Pond decommissioning.

  7. TECHNICAL BASIS FOR THE NUCLEAR CRITICALITY REPRESENTATIVE ACCIDENT & ASSOCIATED REPRESENTED HAZARDOUS CONDITIONS

    SciTech Connect

    GOETZ, T.G.

    2003-06-17

    This document was developed to support the documented safety analysis (DSA) and describes the process and basis for assigning risk bins for the nuclear criticality representative accident and associated hazardous conditions. Revision 1 incorporates ORP IRT comments to enhance the technical presentation and also makes editorial changes. This technical basis document was developed to support the documented safety analysis (DSA), and describes the risk binning process and the technical basis for assigning risk bins for the nuclear criticality representative accident and associated hazardous conditions. The purpose of the risk binning process is to determine the need for safety-significant structures, systems, and components (SSC) and technical safety requirement (TSR)-level controls for a given representative accident or represented hazardous condition based on an evaluation of the frequency and consequence.

  8. Mortality associated with chronic external radiation exposure in the French combined cohort of nuclear workers.

    PubMed

    Metz-Flamant, C; Laurent, O; Samson, E; Caër-Lorho, S; Acker, A; Hubert, D; Richardson, D B; Laurier, D

    2013-09-01

    The long-term effects of protracted low level ionising radiation exposure are investigated in a combined analysis of French nuclear workers employed by the Commissariat à l'Energie Atomique (CEA), AREVA Nuclear Cycle (AREVA NC) and Electricité de France (EDF). Associations between cumulative external radiation dose and mortality due to solid cancers, leukaemia and circulatory disease were examined. All workers hired by CEA, AREVA NC and EDF between 1950 and 1994 who were employed for at least 1 year, badge-monitored for radiation exposure and alive on 1 January 1968 were included. Individual data of annual exposure to penetrating photons (X-rays and gamma rays) were reconstructed for each worker. Estimates of radiation dose-mortality associations were obtained using a linear excess relative risk (ERR) Poisson regression model. Among the 59 021 nuclear workers, 2312 died of solid cancer, 78 of leukaemia and 1468 of circulatory diseases during the 1968-2004 period. Approximately 72% of the cohort had a non-zero cumulative radiation dose estimate, with a mean cumulative dose of 22.5 mSv. Positive but non-significant ERR/Sv were observed for all solid cancers, leukaemia excluding chronic lymphocytic leukaemia (CLL), ischaemic heart diseases and cerebrovascular diseases. A significant ERR/Sv was found for myeloid leukaemia. This is the first combined analysis of major French cohorts of nuclear workers. Results were consistent with risks estimated in other nuclear worker cohorts and illustrate the potential of a further joint international study to yield direct risk estimates in support to radiation protection standards.

  9. Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

    SciTech Connect

    Fuentes-Mera, Lizeth; Rodriguez-Munoz, Rafael; Gonzalez-Ramirez, Ricardo; Garcia-Sierra, Francisco; Gonzalez, Everardo; Mornet, Dominique; Cisneros, Bulmaro . E-mail: bcisnero@cinvestav.mx

    2006-10-01

    Dystrophin is an essential component in the assembly and maintenance of the dystrophin-associated protein complex (DAPC), which includes members of the dystroglycan, syntrophin, sarcoglycan and dystrobrevin protein families. Distinctive complexes have been described in the cell membrane of different tissues and cultured cells. In this work, we report the identification and characterization of a novel DAPC present in the nuclei of HeLa cells, which contains dystrophin Dp71 as a key component. Using confocal microscopy and cell fractionation analyses, we found the presence of Dp71, {beta}-sarcoglycan, {beta}-dystroglycan, {alpha}- and {beta}-syntrophin, {alpha}1- and {beta}-dystrobrevin and nNOS in the nuclei of HeLa cells. Furthermore, we demonstrated by co-immunoprecipitation experiments that most of these proteins form a complex in the nuclear compartment. Next, we analyze the possible association of the nuclear DAPC with the nuclear matrix. We found the presence of Dp71, {beta}-dystroglycan, nNOS, {beta}-sarcoglycan, {alpha}/{beta} syntrophin, {alpha}1-dystrobrevin and {beta}-dystrobrevin in the nuclear matrix protein fractions and in situ nuclear matrix preparations from HeLa cells. Moreover, we found that Dp71, {beta}-dystroglycan and {beta}-dystrobrevin co-immunoprecipitated with the nuclear matrix proteins lamin B1 and actin. The association of members of the nuclear DAPC with the nuclear matrix indicates that they may work as scaffolding proteins involved in nuclear architecture.

  10. David Haussler, Ph.D., Lectures on Cancer Genomics - TCGA

    Cancer.gov

    In this lecture, Dr. David Haussler provides a historical overview of the field of genomics leading up to TCGA, including the Cancer Genomics Hub at the University of California, Santa Cruz, and the TCGA Pan-Cancer initiative.

  11. 2. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE WITH MANURE PIT IN FOREGROUND - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  12. 19. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR EAST WING LOOKING NORTH - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  13. 10. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE OF EAST WING - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  14. 24. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR LOOKING EAST-SOUTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  15. 5. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH FACADE OF WEST WING FROM EAST NORTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  16. 18. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR EAST WING LOOKING NORTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  17. 9. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 EAST FACADE, PART OF NORTH FACADE, TAKEN FROM NORTHWEST - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  18. 2. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH ELEVATION OF CENTRAL PORTION - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  19. 1. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH ELEVATION OF CENTRAL PORTION, CLOSER - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  20. 23. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR CENTRAL ROOM LOOKING WEST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  1. 6. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH FACADE OF WEST WING FROM NORTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  2. 11. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 EAST FACADE, PART OF NORTH FACADE, SOUTH DAIRY BARN IN BACKGROUND, WITH FIELD IN FOREGROUND - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  3. 13. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH CENTRAL ENTRANCE/BREEZEWAY - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  4. 12. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 EAST FACADE, PART OF NORTH FACADE, SOUTH DAIRY BARN IN BACKGROUND - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  5. 5. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE OF CENTRAL PORTION, OBLIQUE VIEW - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  6. 14. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR WEST WING LOOKING NORTHEAST - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  7. 11. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE OF WEST WING - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  8. 21. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR EAST WING LOOKING SOUTH - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  9. 22. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR CENTRAL STAIR LANDING LOOKING NORTH - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  10. 12. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 LOOKING NORTHEAST TO BREEZEWAY BETWEEN BARN AND MILKHOUSE - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  11. 9. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH AND EAST FACADES OF EAST WING - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  12. 25. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR EAST ROOM LOOKING TO SOUTHWEST CORNER - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  13. 20. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR EAST WING LOOKING SOUTHWEST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  14. 7. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH FACADE CENTRAL DOORS - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  15. David Simpson Receives 2012 Waldo E. Smith Medal: Citation

    NASA Astrophysics Data System (ADS)

    Lerner-Lam, Arthur

    2013-01-01

    David Simpson was awarded the 2012 Waldo E. Smith Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is for "extraordinary service to geophysics".

  16. 2. David Ames, Photographer, October 1982 VIEW EAST SHOWING WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. David Ames, Photographer, October 1982 VIEW EAST SHOWING WEST (FRONT) ELEVATION - Jacob Dingee House, 105 East Seventh Street (moved to 500 Block North Market Street), Wilmington, New Castle County, DE

  17. Interview With the 2002 Caldecott Medal Winner, David Wiesner.

    ERIC Educational Resources Information Center

    Giorgis, Cyndi; Johnson, Nancy J.

    2003-01-01

    Discusses David Wiesner, the 2002 Caldecott Medal Winner, and includes excerpts of an interview with him. Notes that Wiesner's books appeal to the imagination and often use art elements such as scale. Details the winning book, "The Three Pigs." (PM)

  18. 12. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Historic American Buildings Survey, David Aronow, Photographer circa 1924, VIEW OF THE CENTRAL COURT WITH THE FOUNTAIN AND TIFFANY VASES IN NICHES. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  19. 9. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Historic American Buildings Survey, David Aronow, Photographer circa 1924, LIVING ROOM SHOWING LIGHTING FIXTURES OF TIFFANY'S DESIGN. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  20. 20. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Historic American Buildings Survey, David Aronow, Photographer circa 1924, 'THE SPRING' ONE OF SEVEN FOUNTAINS ON TIFFANY ESTATE. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  1. 16. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. Historic American Buildings Survey, David Aronow, Photographer circa 1924, TERRACE OVERLOOKING COLD SPRING HARBOR WITH VIEW OF 'TIFFANY TOWER'. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  2. 5. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey, David Aronow, Photographer circa 1924, DETAIL OF ENTRANCE AND BELLTOWER ON FRONT ELEVATION. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  3. 7. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Historic American Buildings Survey, David Aronow, Photographer circa 1924, DETAIL OF MAIN ENTRANCE WITH COLD SPRING HARBOR IN BACKGROUND. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  4. 8. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Historic American Buildings Survey, David Aronow, Photographer circa 1924, LIVING ROOM WITH TIFFANY STAINED GLASS WINDOWS INCLUDING 'FEEDING THE FLAMINGOES,' 'THE FOUR SEASONS,' AND 'THE BATHERS'. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  5. 19. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Historic American Buildings Survey, David Aronow, Photographer circa 1924, INTERIOR OF TIFFANY CHAPEL SHOWING STAINED GLASS WINDOW. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  6. 11. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Historic American Buildings Survey, David Aronow, Photographer circa 1924, CENTRAL COURT WITH PORTRAIT OF TIFFANY BY SOROLLA. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  7. An Interview with Author/Screen Writer David Klass.

    ERIC Educational Resources Information Center

    Carroll, Sissi

    2002-01-01

    Presents an interview with Author/Screen Writer David Klass. Discusses his dual role as young adult author and Hollywood screenwriter. Illuminates important differences that Klass finds when working as writer of young adult books and as a screenwriter. (SG)

  8. Interview With the 2002 Caldecott Medal Winner, David Wiesner.

    ERIC Educational Resources Information Center

    Giorgis, Cyndi; Johnson, Nancy J.

    2003-01-01

    Discusses David Wiesner, the 2002 Caldecott Medal Winner, and includes excerpts of an interview with him. Notes that Wiesner's books appeal to the imagination and often use art elements such as scale. Details the winning book, "The Three Pigs." (PM)

  9. Nuclear Survivin Expression in Mantle Cell Lymphoma Is Associated with Cell Proliferation and Survival

    PubMed Central

    Martinez, Antonio; Bellosillo, Beatriz; Bosch, Francesc; Ferrer, Ana; Marcé, Silvia; Villamor, Neus; Ott, German; Montserrat, Emili; Campo, Elias; Colomer, Dolors

    2004-01-01

    Survivin is a member of the inhibitor of apoptosis protein family that is expressed in G2/M phase. Survivin is overexpressed and associated with parameters of poor prognosis in different human tumors. The role of survivin in the pathogenesis of mantle cell lymphoma (MCL) was examined in a series of typical and blastoid tumors. Survivin was detected as a nuclear pattern in a variable number of tumor cells. Mitotic figures were always positive with a strong delineation of the chromosomes. Western blot analysis confirmed the presence of survivin only in nuclear fractions. Protein expression detected by immunohistochemistry correlated with mRNA levels analyzed by quantitative real-time reverse transcription-polymerase chain reaction (P < 0.0001). Survivin expression levels were higher in blastoid MCL variants (P < 0.0001) and were associated with the proliferative activity (P = 0.001), but not with the ploidy status of the tumors. The number of apoptotic cells was independent of survivin or Ki-67 expression. Overall survival was significantly shorter in patients with high survivin expression. However, in a multivariate analysis, proliferative index was a better predictor of survival than survivin score. These findings indicate that survivin is commonly expressed in MCL with a nuclear and mitotic pattern. The expression levels are strongly associated with the proliferative activity of the tumors and the survival of the patients, suggesting a potential role in cell cycle regulation and tumor progression. PMID:14742256

  10. V-myc- and c-myc-encoded proteins are associated with the nuclear matrix.

    PubMed Central

    Eisenman, R N; Tachibana, C Y; Abrams, H D; Hann, S R

    1985-01-01

    A series of extraction procedures were applied to avian nuclei which allowed us to define three types of association of v-myc- and c-myc-encoded proteins with nuclei: (i) a major fraction (60 to 90%) which is retained in DNA- and RNA-depleted nuclei after low- and high-salt extraction, (ii) a small fraction (1%) released during nuclease digestion of DNA in intact nuclei in the presence of low-salt buffer, and (iii) a fraction of myc protein (less than 10%) extractable with salt or detergents and found to have affinity for both single- and double-stranded DNA. Immunofluorescence analysis with anti-myc peptide sera on cells extracted sequentially with nucleases and salts confirmed the idea that myc proteins were associated with a complex residual nuclear structure (matrix-lamin fraction) which also contained avian nuclear lamin protein. Dispersal of myc proteins into the cytoplasm was found to occur during mitosis. Both c-myc and v-myc proteins were associated with the matrix-lamin, suggesting that the function of myc may relate to nuclear structural organization. Images PMID:3872410

  11. ELYS/MEL-28 Chromatin Association Coordinates Nuclear Pore Complex Assembly and Replication Licensing

    PubMed Central

    Gillespie, Peter J.; Khoudoli, Guennadi A.; Stewart, Graeme; Swedlow, Jason R.; Blow, J. Julian

    2007-01-01

    Summary Xenopus egg extract supports all the major cell-cycle transitions in vitro. We have used a proteomics approach to identify proteins whose abundance on chromatin changes during the course of an in vitro cell cycle. One of the proteins we identified was ELYS/MEL-28, which has recently been described as the earliest-acting factor known to be required for nuclear pore complex (NPC) assembly [1–4]. ELYS interacts with the Nup107-160 complex and is required for its association with chromatin. ELYS contains an AT-hook domain, which we show binds to chromatin with a high affinity. This domain can compete with full-length ELYS for chromatin association, thereby blocking NPC assembly. This provides evidence that ELYS interacts directly with chromatin and that this interaction is essential for NPC assembly and compartmentalization of chromosomal DNA within the cell. Furthermore, we detected a physical association on chromatin between ELYS and the Mcm2-7 replication-licensing proteins. ELYS chromatin loading, NPC assembly, and nuclear growth were delayed when Mcm2-7 was prevented from loading onto chromatin. Because nuclear assembly is required to shut down licensing prior to entry into S phase, our results suggest a mechanism by which these two early cell-cycle events are coordinated with one another. PMID:17825564

  12. Adenovirus DNA is associated with the nuclear matrix of infected cells.

    PubMed Central

    Younghusband, H B; Maundrell, K

    1982-01-01

    Viral DNA was found to be tightly associated with the nuclear matrix from HeLa cells lytically infected with human adenovirus type 5. The bound viral DNA, like cell DNA, was resistant to nonionic detergent and to extraction with high-salt (2 M NaCl) solution. However, whereas over 95% of the cell DNA was recovered in the matrix fraction, the amount of associated viral DNA varied during infection. Throughout the lytic cycle, the amount of matrix-associated adenovirus type 5 DNA increased until it reached a plateau level at 20 to 24 h after infection. At this stage, the matrix-bound DNA represented 87% of the total viral DNA; after this stage, additional newly synthesized viral DNA accumulated as non-matrix-associated DNA. DNase digestion studies revealed that all viral DNA sequences were equally represented in the matrix-bound DNA both early and late in infection; thus, unlike cell DNA, there seem to be no preferred attachment sites on the viral genome. An enrichment of viral DNA relative to cell DNA was found in the matrix-associated DNA after extensive DNase I digestion. This finding, together with an in situ hybridization study, suggests that the viral DNA is more intimately associated with the nuclear matrix than is cell DNA and probably does not exist in extended loops. Images PMID:6287038

  13. On the validity of within-nuclear-family genetic association analysis in samples of extended families.

    PubMed

    Bureau, Alexandre; Duchesne, Thierry

    2015-12-01

    Splitting extended families into their component nuclear families to apply a genetic association method designed for nuclear families is a widespread practice in familial genetic studies. Dependence among genotypes and phenotypes of nuclear families from the same extended family arises because of genetic linkage of the tested marker with a risk variant or because of familial specificity of genetic effects due to gene-environment interaction. This raises concerns about the validity of inference conducted under the assumption of independence of the nuclear families. We indeed prove theoretically that, in a conditional logistic regression analysis applicable to disease cases and their genotyped parents, the naive model-based estimator of the variance of the coefficient estimates underestimates the true variance. However, simulations with realistic effect sizes of risk variants and variation of this effect from family to family reveal that the underestimation is negligible. The simulations also show the greater efficiency of the model-based variance estimator compared to a robust empirical estimator. Our recommendation is therefore, to use the model-based estimator of variance for inference on effects of genetic variants.

  14. Characterization Report for the David Witherspoon Screen Art Site

    SciTech Connect

    Phyllis C. Weaver

    2011-01-31

    The U.S. Department of Energy (DOE) Oak Ridge Office (ORO) of Environmental Management (EM) requested the technical assistance of Oak Ridge Institute for Science and Education (ORISE) to characterize a tract of land associated with the David Witherspoon, Incorporated (DWI) Volunteer Equipment and Supply Company (VESC). This tract of land (hereinafter referred to as Screen Arts) is located in the Vestal Community in the 2000-block of Maryville Pike in south Knoxville, Tennessee, as shown in Figure A-1. This tract of land has been used primarily to store salvaged equipment and materials for resale, recycle, or for disposal in the former landfill once operated by DWI. The DWI Site industrial landfill and metal recycling business had been permitted by the Tennessee Division of Radiological Health to accept low-level radiologically contaminated metals. DWI received materials and equipment associated with operations from DOE sites, including those in Oak Ridge, Tennessee; Paducah, Kentucky; and Portsmouth, Ohio. It is likely that items stored at Screen Arts may have contained some residual radiological materials.

  15. Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

    SciTech Connect

    Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna; Adams, Matthew; High, Alec S.; Johnson, Colin A.; Robinson, Philip A.

    2013-02-01

    HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.

  16. Low nuclear proliferative activity is associated with nonmetastatic islet cell tumors.

    PubMed

    Jorda, Merce; Ghorab, Zeina; Fernandez, Gustavo; Nassiri, Mehdi; Hanly, Andrew; Nadji, Mehrdad

    2003-02-01

    Traditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression. To evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs. We studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (<5% of cells staining positively), intermediate (5%-25% of cells staining positively), or high (>25% of cells staining positively). The majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P <.001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors. An ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular

  17. THE ATTRACTIVENESS OF MATERIAS ASSOCIATED WITH THORIUM-BASED NUCLEAR FUEL CYCLES FOR PHWRS

    SciTech Connect

    Prichard, Andrew W.; Niehus, Mark T.; Collins, Brian A.; Bathke, Charles G.; Ebbinghaus, Bartley B.; Hase, Kevin R.; Sleaford, Brad W.; Robel, Martin; Smith, Brian W.

    2011-07-17

    This paper reports the continued evaluation of the attractiveness of materials mixtures containing special nuclear materials (SNM) associated with thorium based nuclear fuel cycles. Specifically, this paper examines a thorium fuel cycle in which a pressurized heavy water reactor (PHWR) is fueled with mixtures of natural uranium/233U/thorium. This paper uses a PHWR fueled with natural uranium as a base fuel cycle, and then compares material attractiveness of fuel cycles that use 233U/thorium salted with natural uranium. The results include the material attractiveness of fuel at beginning of life (BoL), end of life (EoL), and the number of fuel assemblies required to collect a bare critical mass of plutonium or uranium. This study indicates what is required to render the uranium as having low utility for use in nuclear weapons; in addition, this study estimates the increased number of assemblies required to accumulate a bare critical mass of plutonium that has a higher utility for use in nuclear weapons. This approach identifies that some fuel cycles may be easier to implement the International Atomic Energy Agency (IAEA) safeguards approach and have a more effective safeguards by design outcome. For this study, approximately one year of fuel is required to be reprocessed to obtain one bare critical mass of plutonium. Nevertheless, the result of this paper suggests that all spent fuel needs to be rigorously safeguarded and provided with high levels of physical protection. This study was performed at the request of the United States Department of Energy /National Nuclear Security Administration (DOE/NNSA). The methodology and key findings will be presented.

  18. Downregulation of Iduna is associated with AIF nuclear translocation in neonatal brain after hypoxia-ischemia.

    PubMed

    Yang, Xiaoxia; Cheng, Jianhua; Gao, Yubo; Ding, Juan; Ni, Xinli

    2017-03-27

    In adult stroke models, the neuroprotective protein, Iduna, inhibits poly (ADP-ribose) polymerase-1 (PARP-1)-dependent cell death by decreasing apoptosis-inducing factor (AIF) nuclear translocation. Because the PARP1-dependent pathway and Iduna, which promotes AIF degradation, contribute to hypoxic-ischemic (HI) brain damage in the immature brain, we examined the relationship between Iduna expression and AIF nuclear translocation in the cerebral cortex of postnatal day 7 rats after HI. Ninety rats were divided into three groups: sham, 1-h hypoxia and 2-h hypoxia. The HI insult was induced by permanent ligation of the left common carotid artery plus 1 or 2h of hypoxia. Brain damage pathological features were evaluated by hematoxylin and eosin staining, Nissl staining, transmission electron microscopy, TUNEL staining and immunofluorescence. Immunohistochemistry and western blot analysis were used to assess protein expression and ubiquitination status of AIF. The interaction between Iduna and AIF was tested by co-immunoprecipitation. Learning and memory were analyzed by the Morris water maze test. Compared with sham animals, the number of surviving neurons in the cerebral cortex decreased, and cell damage and DNA breakage were severe in rats with HI, with worse damage in the 2-h group. Iduna expression significantly decreased, whereas nuclear AIF expression increased. Furthermore, Iduna downregulation negatively correlated with nuclear AIF abundance in the 2-h HI group (r=-0.950; P<0.0001). Additionally, learning and memory ability decreased with hypoxic time. These results suggest that AIF nuclear translocation and neuronal cell death are associated with Iduna loss after severe HI in the immature brain.

  19. The latency-associated nuclear antigen of Kaposi sarcoma–associated herpesvirus induces B cell hyperplasia and lymphoma

    PubMed Central

    Fakhari, Farnaz D.; Jeong, Joseph H.; Kanan, Yogita; Dittmer, Dirk P.

    2006-01-01

    Kaposi sarcoma–associated herpesvirus (KSHV) is a human lymphotropic herpesvirus. It is implicated in B cell neoplasias such as primary effusion lymphoma and multicentric Castleman disease in AIDS patients. The KSHV latency-associated nuclear antigen (LANA) is consistently expressed in all KSHV-associated tumor cells and was shown to bind the tumor suppressor proteins p53 and pRb. To test LANA’s contribution to lymphomagenesis in vivo we generated transgenic mice expressing LANA under the control of its own promoter, which is B cell specific. All of the transgenic mice developed splenic follicular hyperplasia due to an expansion of IgM+IgD+ B cells and showed increased germinal center formation. We also observed lymphomas, implying that LANA can activate B cells and provide the first step toward lymphomagenesis. PMID:16498502

  20. Potential Signatures of Semi-volatile Compounds Associated With Nuclear Processing

    SciTech Connect

    Probasco, Kathleen M.; Birnbaum, Jerome C.; Maughan, A. D.

    2002-06-01

    Semi-volatile chemicals associated with nuclear processes (e.g., the reprocessing of uranium to produce plutonium for nuclear weapons, or the separation of actinides from processing waste streams), can provide sticky residues or signatures that will attach to piping, ducting, soil, water, or other surface media. Volatile compounds, that are more suitable for electro-optical sensing, have been well studied. However, the semi-volatile compounds have not been well documented or studied. A majority of these semi-volatile chemicals are more robust than typical gaseous or liquid chemicals and can have lifetimes of several weeks, months, or years in the environment. However, large data gaps exist concerning these potential signature compounds and more research is needed to fill these data gaps so that important signature information is not overlooked or discarded. This report investigates key semi-volatile compounds associated with nuclear separations, identifies available chemical and physical properties, and discusses the degradation products that would result from hydrolysis, radiolysis and oxidation reactions on these compounds.

  1. Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies.

    PubMed

    Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna; Adams, Matthew; High, Alec S; Johnson, Colin A; Robinson, Philip A

    2013-02-01

    HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies.

  2. Invariant Delineation of Nuclear Architecture in Glioblastoma Multiforme for Clinical and Molecular Association

    PubMed Central

    Han, Ju; Borowsky, Alexander; Loss, Leandro; Gray, Joe W.; Spellman, Paul T.

    2013-01-01

    Automated analysis of whole mount tissue sections can provide insights into tumor subtypes and the underlying molecular basis of neoplasm. However, since tumor sections are collected from different laboratories, inherent technical and biological variations impede analysis for very large datasets such as The Cancer Genome Atlas (TCGA). Our objective is to characterize tumor histopathology, through the delineation of the nuclear regions, from hematoxylin and eosin (H&E) stained tissue sections. Such a representation can then be mined for intrinsic subtypes across a large dataset for prediction and molecular association. Furthermore, nuclear segmentation is formulated within a multi-reference graph framework with geodesic constraints, which enables computation of multidimensional representations, on a cell-by-cell basis, for functional enrichment and bioinformatics analysis. Here, we present a novel method, Multi-Reference Graph Cut (MRGC), for nuclear segmentation that overcomes technical variations associated with sample preparation by incorporating prior knowledge from manually annotated reference images and local image features. The proposed approach has been validated on manually annotated samples and then applied to a dataset of 377 Glioblastoma Multiforme (GBM) whole slide images from 146 patients. For the GBM cohort, multidimensional representation of the nuclear features and their organization have identified (i) statistically significant subtypes based on several morphometric indices, (ii) whether each subtype can be predictive or not, and (iii) that the molecular correlates of predictive subtypes are consistent with the literature. Data and intermediaries for a number of tumor types (GBM, low grade glial, and kidney renal clear carcinoma) are available at: http://tcga.lbl.gov for correlation with TCGA molecular data. The website also provides an interface for panning and zooming of whole mount tissue sections with/without overlaid segmentation results for

  3. Nuclear COMMD1 Is Associated with Cisplatin Sensitivity in Ovarian Cancer

    PubMed Central

    Wisman, G. Bea A.; Duiker, Evelien; Reyners, Anna K. L.; van der Zee, Ate G. J.; van de Sluis, Bart; van Vugt, Marcel A. T. M.

    2016-01-01

    Copper metabolism MURR1 domain 1 (COMMD1) protein is a multifunctional protein, and its expression has been correlated with patients’ survival in different types of cancer. In vitro studies revealed that COMMD1 plays a role in sensitizing cancer cell lines to cisplatin, however, the mechanism and its role in platinum sensitivity in cancer has yet to be established. We evaluated the role of COMMD1 in cisplatin sensitivity in A2780 ovarian cancer cells and the relation between COMMD1 expression and response to platinum-based therapy in advanced stage high-grade serous ovarian cancer (HGSOC) patients. We found that elevation of nuclear COMMD1 expression sensitized A2780 ovarian cancer cells to cisplatin-mediated cytotoxicity. This was accompanied by a more effective G2/M checkpoint, and decreased protein expression of the DNA repair gene BRCA1, and the apoptosis inhibitor BCL2. Furthermore, COMMD1 expression was immunohistochemically analyzed in two tissue micro-arrays (TMAs), representing a historical cohort and a randomized clinical trial-based cohort of advanced stage HGSOC tumor specimens. Expression of COMMD1 was observed in all ovarian cancer samples, however, specifically nuclear expression of COMMD1 was only observed in a subset of ovarian cancers. In our historical cohort, nuclear COMMD1 expression was associated with an improved response to chemotherapy (OR = 0.167; P = 0.038), although this association could not be confirmed in the second cohort, likely due to sample size. Taken together, these results suggest that nuclear expression of COMMD1 sensitize ovarian cancer to cisplatin, possibly by modulating the G2/M checkpoint and through controlling expression of genes involved in DNA repair and apoptosis. PMID:27788210

  4. David Hartley's psychobiological associationism and the legacy of Aristotle.

    PubMed

    Buckingham, H W; Finger, S

    1997-04-01

    The idea that there are certain "laws" of learning (similarity, contrast, contiguity) can be traced to Aristotle. He maintained that external stimuli cause small movements in the vessels to the dominant heart, the vestiges of which can be linked to one another. Aristotle's laws of learning were incorporated into the writings of Hobbes, Locke, and Berkeley, men who said nothing about the physiological correlates of mental associations. This left the door open for David Hartley to combine mental associationism with the Newtonian idea that sensations can cause minute particle vibrations in the nerves. Hartley's amalgam of psychology, philosophy, and neurology was first presented in 1746, as a "trial balloon" at the end a little-known monograph on a treatment for kidney stones. It was repeated three years later in his better-known Observations on Man. In many ways, modern psychobiological connectionism can be traced back to Hartley's Conjectures of 1746, in which Aristotle's original thoughts were modified with then current ideas about functions of the mind and the nervous system.

  5. David Florida Laboratory: Support for mobile satellite communications

    NASA Technical Reports Server (NTRS)

    Dumoulin, Jean-Guy; Mamen, Rolf

    1995-01-01

    The comprehensive integration and environmental (including RF) test facilities of the Canadian Space Agency's David Florida Laboratory (CSA)(DFL) were used extensively for the MSAT Program. Following a description of the facilities, the paper outlines their application to the qualification of the two MSAT satellites following an overview of the test plan. Particular emphasis is given to passive intermodulation measurement (PIM) demands, which for the MSAT satellites, contributed to the need to extend the anechoic chamber. The extended chamber was also used for an EMC test and SAR signature test of the RADARSAT satellite. The DFL's facilities are being used for additional aspects of mobile satellite communications. One shielded anechoic Extra High Frequency (EHF) chamber and associated test equipment are employed predominantly for measuring the performance of the IRIDIUM satellites' Engineering Model Gateway Moveable Antennas (EM)(GMA). Other chambers are used for testing aeronautical antennas on behalf of Inmarsat. Still others combine thermal and PIM testing. The paper concludes with a review of the test requirements of evolving satcom missions such as Inmarsat Aero-1.

  6. Gene associations: true romance or chance meeting in a nuclear neighborhood?

    PubMed

    Lawrence, Jeanne B; Clemson, Christine M

    2008-09-22

    Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene-gene interactions, communication, and even "romance." However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor-rich speckles (a.k.a., SC35-defined domains). This clustering appears largely stochastic but is impacted by the chromosomal neighborhood of the gene as well as its transcriptional status. The study adds a new twist by examining the same gene in a foreign chromosomal context, providing evidence that this impacts a gene's propensity to form gene-domain (or apparent gene-gene) associations within nuclei.

  7. Gene associations: true romance or chance meeting in a nuclear neighborhood?

    PubMed Central

    Lawrence, Jeanne B.; Clemson, Christine M.

    2008-01-01

    Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene–gene interactions, communication, and even “romance.” However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor–rich speckles (a.k.a., SC35-defined domains). This clustering appears largely stochastic but is impacted by the chromosomal neighborhood of the gene as well as its transcriptional status. The study adds a new twist by examining the same gene in a foreign chromosomal context, providing evidence that this impacts a gene's propensity to form gene–domain (or apparent gene–gene) associations within nuclei. PMID:18809719

  8. FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer.

    PubMed

    Habashy, Hany Onsy; Rakha, Emad A; Aleskandarany, Mohammed; Ahmed, Mohamed Ah; Green, Andrew R; Ellis, Ian O; Powe, Desmond G

    2011-08-01

    Oestrogen receptor (ER)-positive breast cancer (BC) constitutes a heterogeneous group of tumours with regard to outcome and response to therapy. Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and ER-related biological pathways. Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream target of the Akt/PI3K pathway indicating a biological and potential clinical role for FOXO3a in ER-positive BC. In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer. FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1 and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (P < 0.001) and longer distant metastasis free interval (P = 0.001), independently of the well-established breast cancer prognostic factors. In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localisation in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.

  9. Nuclear movement regulated by non-Smad Nodal signaling via JNK is associated with Smad signaling during zebrafish endoderm specification.

    PubMed

    Hozumi, Shunya; Aoki, Shun; Kikuchi, Yutaka

    2017-09-25

    Although asymmetric nuclear positioning is observed during animal development, the regulation and significance of this nuclear positioning in cell differentiation remains poorly understood. Using zebrafish blastulae, we provide evidence that nuclear movement toward the yolk syncytial layer, which comprises extraembryonic tissue, occurs in the first endoderm specified cells during endoderm specification. Nodal signaling is essential for nuclear movement, whereas nuclear envelope proteins are involved in the movement through the microtubule formation. The positioning of the microtubule organizing center, which is proposed to be critical for nuclear movement, is regulated by Nodal signaling and nuclear envelope proteins. The non-Smad JNK signaling pathway, which is downstream of Nodal signaling, regulates nuclear movement independent of the Smad pathway, and this nuclear movement is associated with Smad signal transduction toward the nucleus. Our study provides insights into the function of nuclear movement in Smad signaling toward the nucleus, and could be applied to the control of Transforming Growth Factor-β signaling. © 2017. Published by The Company of Biologists Ltd.

  10. The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

    PubMed

    Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

    2017-09-23

    Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity are markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localizes to the cytoplasm but a fraction of Gpn3R Q279* enters the cell nucleus and inhibits Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells requires a PDZ-binding motif generated by the Q279* mutation. We conclude that this PDZ-binding motif resulting from the Q279* mutation causes Gpn3 nuclear entry, inhibits Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. David Melcher: Award for Distinguished Scientific Early Career Contributions to Psychology.

    PubMed

    2011-11-01

    Presents David Melcher, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For his elegant and groundbreaking work on one of the most important problems in perceptual psychology, the transfer of perceptual representations across eye movements. David Melcher's innovative experiments used perceptual aftereffects to show how remapping of visual locations underlies the creation of the percept of a clear and stable world. His work on the accumulation of memory contributed importantly to the understanding of natural perceptual representations and their neural underpinnings. His elegant reviews of transsaccadic perception communicated to a broad audience the remarkable capacity of the brain to create seamless perceptual representations despite the disruptions produced by eye movements." (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  12. Gold Medal Award for Life Achievement in the Application of Psychology: David W. Johnson.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Application of Psychology is David W. Johnson. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Ribosomal Protein S6 Interacts with the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus ▿

    PubMed Central

    Chen, Wuguo; Dittmer, Dirk P.

    2011-01-01

    The latency-associated nuclear antigen (LANA) is central to the maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) and to the survival of KSHV-carrying tumor cells. In an effort to identify interaction partners of LANA, we purified authentic high-molecular-weight complexes of LANA by conventional chromatography followed by immunoprecipitation from the BC-3 cell line. This is the first analysis of LANA-interacting partners that is not based on forced ectopic expression of LANA. Subsequent tandem mass spectrometry (MS/MS) analysis identified many of the known LANA-interacting proteins. We confirmed LANA's interactions with histones. Three classes of proteins survived our stringent four-step purification procedure (size, heparin, anion, and immunoaffinity chromatography): two heat shock proteins (Hsp70 and Hsp96 precursor), signal recognition particle 72 (SRP72), and 10 different ribosomal proteins. These proteins are likely involved in structural interactions within LANA high-molecular-weight complexes. Here, we show that ribosomal protein S6 (RPS6) interacts with LANA. This interaction is mediated by the N-terminal domain of LANA and does not require DNA or RNA. Depletion of RPS6 from primary effusion lymphoma (PEL) cells dramatically decreases the half-life of full-length LANA. The fact that RPS6 has a well-established nuclear function beyond its role in ribosome assembly suggests that RPS6 (and by extension other ribosomal proteins) contributes to the extraordinary stability of LANA. PMID:21734034

  14. Obituary: David Fulmer Bender, 1913-2004

    NASA Astrophysics Data System (ADS)

    Miller, Sylvia L.

    2004-12-01

    David Fulmer Bender died in San Diego, California, on 13 September 2004, at the age of 91. His heart stopped suddenly while he was dancing. His pioneering work in establishing comprehensive, computer-accessible ephemerides of asteroids and comets found many applications, including the first-ever visit to an asteroid, Gaspra, by an interplanetary spacecraft. Dave was born in Reno, Nevada, on 10 February 1913, to Homer Charles Bender and Susan Bowers Bender. The family moved to Spokane, Washington, while Dave was very young. His father was a civil engineer and a graduate of MIT, who helped design bridges and dams throughout the Northwest, including the Grand Coolie Dam. Dave had a brother, Phillip (now deceased), who was one year younger. Advancing rapidly in the Spokane school system, Dave finished high school when he was 15 years old. At 16 he moved to Pasadena, California, and began his studies at the California Institute of Technology (Caltech). In addition to pursuing his course work, he was active in track and football, a tendency toward physical exercise that stayed with him for the rest of his life. It was probably during these years that Dave heard a lecture by Albert Einstein, as mentioned to colleagues many years later. Dave received a BS degree in physics in 1933, an MS in 1934, and a PhD in 1937, all from Caltech. His dissertation was entitled, "The Index of Refraction of Air in the Photographic Infrared." During his sophomore year he found his way to Pomona College in Claremont, California, where he met his future wife, Elizabeth Boyden at a social gathering. They were married in 1935. Dave's academic career spanned the years from 1937 to 1970, initially at Louisiana State University, Vanderbilt University, and then Fisk. As a life-long pacifist and conscientious objector, Dave served alternate duty during World War II. In 1946 he joined the faculty of the physics department at Whittier College in California, where he became the department chair and

  15. AIRE-induced apoptosis is associated with nuclear translocation of stress sensor protein GAPDH

    SciTech Connect

    Liiv, Ingrid; Haljasorg, Uku; Kisand, Kai; Maslovskaja, Julia; Laan, Martti; Peterson, Paert

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer AIRE induces apoptosis in epithelial cells. Black-Right-Pointing-Pointer CARD domain of AIRE is sufficient for apoptosis induction. Black-Right-Pointing-Pointer AIRE induced apoptosis involves GAPDH translocation to the nuclei. Black-Right-Pointing-Pointer Deprenyl inhibits AIRE induced apoptosis. -- Abstract: AIRE (Autoimmune Regulator) has a central role in the transcriptional regulation of self-antigens in medullary thymic epithelial cells, which is necessary for negative selection of autoreactive T cells. Recent data have shown that AIRE can also induce apoptosis, which may be linked to cross-presentation of these self-antigens. Here we studied AIRE-induced apoptosis using AIRE over-expression in a thymic epithelial cell line as well as doxycycline-inducible HEK293 cells. We show that the HSR/CARD domain in AIRE together with a nuclear localization signal is sufficient to induce apoptosis. In the nuclei of AIRE-positive cells, we also found an increased accumulation of a glycolytic enzyme, glyceraldehyde-3-phosphate (GAPDH) reflecting cellular stress and apoptosis. Additionally, AIRE-induced apoptosis was inhibited with an anti-apoptotic agent deprenyl that blocks GAPDH nitrosylation and nuclear translocation. We propose that the AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells.

  16. Super-resolution imaging of nuclear import of adeno-associated virus in live cells

    PubMed Central

    Kelich, Joseph M; Ma, Jiong; Dong, Biao; Wang, Qizhao; Chin, Mario; Magura, Connor M; Xiao, Weidong; Yang, Weidong

    2015-01-01

    Adeno-associated virus (AAV) has been developed as a promising human gene therapy vector. Particularly, recombinant AAV vector (rAAV) achieves its transduction of host cells by crossing at least three physiological barriers including plasma membrane, endosomal membrane, and nuclear envelope (NE). So far, the AAV transduction mechanism has not been explored thoroughly at the single viral particle level. In this study, we employed high-speed super-resolution single-point edge-excitation sub-diffraction (SPEED) microscopy to map the events of single rAAV2 particles infecting live human cells with an unprecedented spatiotemporal resolution of 9–12 nm and 2–20 ms. Data reveal that rAAV2 particles are imported through nuclear pore complexes (NPCs) rather than nuclear membrane budding into the nucleus. Moreover, approximately 17% of the rAAV2 molecules starting from the cytoplasm successfully transverse the NPCs to reach the nucleoplasm, revealing that the NPCs act as a strict selective step for AAV delivery. This study lastly suggests a new pathway to improve AAV vectors for human gene therapy. PMID:26665132

  17. Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear matrix.

    PubMed

    Yun, Jing-Ping; Chew, Eng Ching; Liew, Choong-Tsek; Chan, John Y H; Jin, Mei-Lin; Ding, Ming-Xiao; Fai, Yam Hin; Li, H K Richard; Liang, Xiao-Man; Wu, Qiu-Liang

    2003-12-15

    It has become obvious that a better understanding and potential elucidation of the nucleolar phosphoprotein B23 involving in functional interrelationship between nuclear organization and gene expression. In present study, protein B23 expression were investigated in the regenerative hepatocytes at different periods (at days 0, 1, 2, 3, 4, 7) during liver regeneration after partial hepatectomy on the rats with immunohistochemistry and Western blot analysis. Another experiment was done with immunolabeling methods and two-dimensional (2-D) gel electrophoresis for identification of B23 in the regenerating hepatocytes and HepG2 cells (hepatoblastoma cell line) after sequential extraction with detergents, nuclease, and salt. The results showed that its expression in the hepatocytes had a locative move and quantitative change during the process of liver regeneration post-operation. Its immunochemical localization in the hepatocytes during the process showed that it moved from nucleoli of the hepatocytes in the stationary stage to nucleoplasm, cytoplasm, mitotic spindles, and mitotic chromosomes of the hepatocytes in the regenerating livers. It was quantitatively increased progressively to peak level at day 3 post-operation and declined gradually to normal level at day 7. It was detected in nuclear matrix protein (NMP) composition extracted from the regenerating hepatocytes and HepG2 cells and identified with isoelectric point (pI) value of 5.1 and molecular weight of 40 kDa. These results indicated that B23 was a proliferate shuttle protein involving in cell cycle and cell proliferation associated with nuclear matrix.

  18. AIRE-induced apoptosis is associated with nuclear translocation of stress sensor protein GAPDH.

    PubMed

    Liiv, Ingrid; Haljasorg, Uku; Kisand, Kai; Maslovskaja, Julia; Laan, Martti; Peterson, Pärt

    2012-06-22

    AIRE (Autoimmune Regulator) has a central role in the transcriptional regulation of self-antigens in medullary thymic epithelial cells, which is necessary for negative selection of autoreactive T cells. Recent data have shown that AIRE can also induce apoptosis, which may be linked to cross-presentation of these self-antigens. Here we studied AIRE-induced apoptosis using AIRE over-expression in a thymic epithelial cell line as well as doxycycline-inducible HEK293 cells. We show that the HSR/CARD domain in AIRE together with a nuclear localization signal is sufficient to induce apoptosis. In the nuclei of AIRE-positive cells, we also found an increased accumulation of a glycolytic enzyme, glyceraldehyde-3-phosphate (GAPDH) reflecting cellular stress and apoptosis. Additionally, AIRE-induced apoptosis was inhibited with an anti-apoptotic agent deprenyl that blocks GAPDH nitrosylation and nuclear translocation. We propose that the AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Nucleolus association of chromosomal domains is largely maintained in cellular senescence despite massive nuclear reorganisation

    PubMed Central

    Dillinger, Stefan

    2017-01-01

    Mammalian chromosomes are organized in structural and functional domains of 0.1–10 Mb, which are characterized by high self-association frequencies in the nuclear space and different contact probabilities with nuclear sub-compartments. They exhibit distinct chromatin modification patterns, gene expression levels and replication timing. Recently, nucleolus-associated chromosomal domains (NADs) have been discovered, yet their precise genomic organization and dynamics are still largely unknown. Here, we use nucleolus genomics and single-cell experiments to address these questions in human embryonic fibroblasts during replicative senescence. Genome-wide mapping reveals 1,646 NADs in proliferating cells, which cover about 38% of the annotated human genome. They are mainly heterochromatic and correlate with late replicating loci. Using Hi-C data analysis, we show that interactions of NADs dominate interphase chromosome contacts in the 10–50 Mb distance range. Interestingly, only minute changes in nucleolar association are observed upon senescence. These spatial rearrangements in subdomains smaller than 100 kb are accompanied with local transcriptional changes. In contrast, large centromeric and pericentromeric satellite repeat clusters extensively dissociate from nucleoli in senescent cells. Accordingly, H3K9me3-marked heterochromatin gets remodelled at the perinucleolar space as revealed by immunofluorescence analyses. Collectively, this study identifies connections between the nucleolus, 3D genome structure, and cellular aging at the level of interphase chromosome organization. PMID:28575119

  20. National Academy of Sciences survey on risks associated with nuclear power

    SciTech Connect

    Buchanan, J.R.

    1980-01-01

    A critical review of the literature pertaining to the risks associated with nuclear electric power was sponsored by the Committee on Science and Public Policy of the National Academy of Sciences. Although the full report (consisting of over 25 chapters) has not yet been published, this paper presents highlights from the Summary and Synthesis Chapter, which was released separately. Of the risks whose magnitudes can be estimated with reasonable accuracy, the most serious is the exposure of future generations to /sup 14/C from reactors and reprocessing plants. Prospects are good for reducing this risk considerably, since carbon can be collected and stored as waste.

  1. Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence.

    PubMed

    Smith, Carolyn L; Migliaccio, Ilenia; Chaubal, Vaishali; Wu, Meng-Fen; Pace, Margaret C; Hartmaier, Ryan; Jiang, Shiming; Edwards, Dean P; Gutiérrez, M Carolina; Hilsenbeck, Susan G; Oesterreich, Steffi

    2012-11-01

    Silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), also known as nuclear corepressor 2 (NCOR2) is a transcriptional corepressor for multiple members of the nuclear receptor superfamily of transcription factors, including estrogen receptor-α (ERα). In the classical model of corepressor action, SMRT binds to antiestrogen-bound ERα at target promoters and represses ERα transcriptional activity and gene expression. Herein SMRT mRNA and protein expression was examined in a panel of 30 breast cancer cell lines. Expression of both parameters was found to vary considerably amongst lines and the correlation between protein and mRNA expression was very poor (R (2) = 0.0775). Therefore, SMRT protein levels were examined by immunohistochemical staining of a tissue microarray of 866 patients with stage I-II breast cancer. Nuclear and cytoplasmic SMRT were scored separately according to the Allred score. The majority of tumors (67 %) were negative for cytoplasmic SMRT, which when detected was found at very low levels. In contrast, nuclear SMRT was broadly detected. There was no significant difference in time to recurrence (TTR) according to SMRT expression levels in the ERα-positive tamoxifen-treated patients (P = 0.297) but the difference was significant in the untreated patients (P = 0.01). In multivariate analysis, ERα-positive tamoxifen-untreated patients with high nuclear SMRT expression (SMRT 5-8, i.e., 2nd to 4th quartile) had a shorter TTR (HR = 1.94, 95 % CI, 1.24-3.04; P = 0.004) while there was no association with SMRT expression for ERα-positive tamoxifen-treated patients. There was no association between SMRT expression and overall survival for patients, regardless of whether they received tamoxifen. Thus while SMRT protein expression was not predictive of outcome after antiestrogen therapy, it may have value in predicting tumor recurrence in patients not receiving adjuvant tamoxifen therapy.

  2. Anhydrobiosis-Associated Nuclear DNA Damage and Repair in the Sleeping Chironomid: Linkage with Radioresistance

    PubMed Central

    Vanyagina, Veronica; Malutina, Ludmila; Cornette, Richard; Sakashita, Tetsuya; Hamada, Nobuyuki; Kikawada, Takahiro; Kobayashi, Yasuhiko; Okuda, Takashi

    2010-01-01

    Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3–4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by

  3. Anhydrobiosis-associated nuclear DNA damage and repair in the sleeping chironomid: linkage with radioresistance.

    PubMed

    Gusev, Oleg; Nakahara, Yuichi; Vanyagina, Veronica; Malutina, Ludmila; Cornette, Richard; Sakashita, Tetsuya; Hamada, Nobuyuki; Kikawada, Takahiro; Kobayashi, Yasuhiko; Okuda, Takashi

    2010-11-16

    Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions ((4)He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3-4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by

  4. Identifying Novel Transcriptional and Epigenetic Features of Nuclear Lamina-associated Genes.

    PubMed

    Wu, Feinan; Yao, Jie

    2017-12-01

    Because a large portion of the mammalian genome is associated with the nuclear lamina (NL), it is interesting to study how native genes resided there are transcribed and regulated. In this study, we report unique transcriptional and epigenetic features of nearly 3,500 NL-associated genes (NL genes). Promoter regions of active NL genes are often excluded from NL-association, suggesting that NL-promoter interactions may repress transcription. Active NL genes with higher RNA polymerase II (Pol II) recruitment levels tend to display Pol II promoter-proximal pausing, while Pol II recruitment and Pol II pausing are not correlated among non-NL genes. At the genome-wide scale, NL-association and H3K27me3 distinguishes two large gene classes with low transcriptional activities. Notably, NL-association is anti-correlated with both transcription and active histone mark levels among genes not significantly enriched with H3K9me3 or H3K27me3, suggesting that NL-association may represent a novel gene repression pathway. Interestingly, an NL gene subgroup is not significantly enriched with H3K9me3 or H3K27me3 and is transcribed at higher levels than the rest of NL genes. Furthermore, we identified distal enhancers associated with active NL genes and reported their epigenetic features.

  5. RDAVIDWebService: a versatile R interface to DAVID.

    PubMed

    Fresno, Cristóbal; Fernández, Elmer A

    2013-11-01

    The RDAVIDWebService package provides a class-based interface from R programs/scripts to fully access/control the database for annotation, visualization and integrated discovery, without the need for human interaction on its Web site (http://david.abcc.ncifcrf.gov). The library enhances the database for annotation, visualization and integrated discovery capabilities for Gene Ontology analysis by means of GOstats-based direct acyclic graph conversion methods, in addition to the usual many-genes-to-many-terms visualization. RDAVIDWebService is available as an R package from the Bioconductor project (www.bioconductor.org) and on the authors' Web site (www.bdmg.com.ar) under GPL-2 license, subjected to the terms of use of DAVID (http://david.abcc.ncifcrf.gov/content.jsp?file=WS.html). cfresno@bdmg.com.ar or efernandez@bdmg.com.ar.

  6. Mental disorder that afflicted King David the Great.

    PubMed

    Ben-Noun, Liubov

    2004-12-01

    This research uses the tools of modern medical science to study ancient descriptions of the symptoms suffered by King David. Biblical texts were examined, with a close study of verses relating to the mental disorder that afflicted King David, the second and greatest King of Israel, who ruled more than 3525 years ago. We include no commentaries, but refer only to the words of the Bible exactly as written. Evaluation of the passages referring to King David indicated that he was afflicted by some mental disorder, and among the many possibilities major depression, dysthymia and minor depression are the most likely. Of these diagnoses, major depression seems the most acceptable. This report suggests that the roots of contemporary psychiatry can be traced back to Biblical times.

  7. Association of Nuclear Localization of a Long Interspersed Nuclear Element-1 Protein in Breast Tumors with Poor Prognostic Outcomes

    PubMed Central

    Harris, Chris R.; Normart, Robin; Yang, Qifeng; Stevenson, Elizabeth; Haffty, Bruce G.; Ganesan, Shridar; Cordon-Cardo, Carlos; Levine, Arnold J.; Tang, Laura H.

    2010-01-01

    Within healthy human somatic cells, retrotransposition by long interspersed nuclear element-1 (also known as LINE-1 or L1) is thought to be held in check by a variety of mechanisms, including DNA methylation and RNAi. The expression of L1-ORF1 protein, which is rarely found in normal tissue, was assayed using antibodies with a variety of clinical cancer specimens and cancer cell lines. L1-ORF1p expression was detected in nearly all breast tumors that the authors examined, and the protein was also present in a high percentage of ileal carcinoids, bladder, and pancreatic neuroendocrine tumors, as well as in a smaller percentage of prostate and colorectal tumors. Tumors generally demonstrated cytoplasmic L1-ORF1p; however, in several breast cancers, L1-ORF1p was nuclear. Patients with breast tumors displaying nuclear L1-ORF1p had a greater incidence of both local recurrence and distal metastases and also showed poorer overall survival when compared with patients with tumors displaying cytoplasmic L1-ORF1p. These data suggest that expression of L1-ORF1p is widespread in many cancers and that redistribution from cytoplasm to nucleus could be a poor prognostic indicator during breast cancer. High expression and nuclear localization of L1-ORF1p may result in a higher rate of L1 retrotransposition, which could increase genomic instability. PMID:20948976

  8. Midwest Nuclear Training Association Annual Nuclear Instructors' Workshop (4th, Columbus, Ohio, October 16-18, 1989).

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document reports the proceedings of a national workshop designed to provide nuclear trainers from the electric power industry with an opportunity to expand and improve their knowledge and skills in the development and implementation of effective training programs. The following papers are included: "Developing Positive Worker Behaviors:…

  9. Genetic analysis of Père David's x red deer interspecies hybrids.

    PubMed

    Tate, M L; Goosen, G J; Patene, H; Pearse, A J; McEwan, K M; Fennessy, P F

    1997-01-01

    Interspecies hybrids provide unique opportunities for fundamental genetic analyses and for genetic improvement of farmed deer. We have bred F1 hybrids by artificial insemination of red deer hinds (Cervus elaphus) with semen from Père David's deer (Elaphurus davidianus). The male and female F1 Père David deer x red deer hybrids were fertile and in matings with red deer have produced over 300 viable backcross hybrids. DNA was collected from the backcross progeny as an international reference panel for gene linkage mapping and to investigate associations between segregating species-specific genetic markers and phenotypic traits. We have measured a range of phenotypic traits in the backcross hybrids and red deer. Several traits appear suitable for genetic analysis using mapped genetic markers, including gestation length, growth rate, live weight, head morphometrics, and tail length. Typically these traits show a large difference between Père David's deer and red deer and a high variance in the backcross so that many individuals have a phenotype outside the range observed in red deer.

  10. High throughput sequencing identifies an imprinted gene, Grb10, associated with the pluripotency state in nuclear transfer embryonic stem cells.

    PubMed

    Li, Hui; Gao, Shuai; Huang, Hua; Liu, Wenqiang; Huang, Huanwei; Liu, Xiaoyu; Gao, Yawei; Le, Rongrong; Kou, Xiaochen; Zhao, Yanhong; Kou, Zhaohui; Li, Jia; Wang, Hong; Zhang, Yu; Wang, Hailin; Cai, Tao; Sun, Qingyuan; Gao, Shaorong; Han, Zhiming

    2017-07-18

    Somatic cell nuclear transfer and transcription factor mediated reprogramming are two widely used techniques for somatic cell reprogramming. Both fully reprogrammed nuclear transfer embryonic stem cells and induced pluripotent stem cells hold potential for regenerative medicine, and evaluation of the stem cell pluripotency state is crucial for these applications. Previous reports have shown that the Dlk1-Dio3 region is associated with pluripotency in induced pluripotent stem cells and the incomplete somatic cell reprogramming causes abnormally elevated levels of genomic 5-methylcytosine in induced pluripotent stem cells compared to nuclear transfer embryonic stem cells and embryonic stem cells. In this study, we compared pluripotency associated genes Rian and Gtl2 in the Dlk1-Dio3 region in exactly syngeneic nuclear transfer embryonic stem cells and induced pluripotent stem cells with same genomic insertion. We also assessed 5-methylcytosine and 5-hydroxymethylcytosine levels and performed high-throughput sequencing in these cells. Our results showed that Rian and Gtl2 in the Dlk1-Dio3 region related to pluripotency in induced pluripotent stem cells did not correlate with the genes in nuclear transfer embryonic stem cells, and no significant difference in 5-methylcytosine and 5-hydroxymethylcytosine levels were observed between fully and partially reprogrammed nuclear transfer embryonic stem cells and induced pluripotent stem cells. Through syngeneic comparison, our study identifies for the first time that Grb10 is associated with the pluripotency state in nuclear transfer embryonic stem cells.

  11. Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status

    PubMed Central

    Kumar, Bhavna; Yadav, Arti; Brown, Nicole V.; Zhao, Songzhu; Cipolla, Michael J.; Wakely, Paul E.; Schmitt, Alessandra C.; Baiocchi, Robert A.; Teknos, Theodoros N.

    2017-01-01

    Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. Our results show that nuclear PRMT5 was associated with poor overall survival (p < 0.012) and these patients had 1.732 times higher hazard of death (95% CI: 1.127–2.661) as compared to patients in whom PRMT5 was not present in the nucleus of the tumors. Nuclear PRMT5 expression was inversely correlated with p16-status (p < 0.001) and was significantly higher in tumor samples from patients who smoked > 10 pack-years (p = 0.013). In addition, nuclear PRMT5 was directly correlated with cyclin D1 (p = 0.0101) and IL-6 expression (p < 0.001). In a subgroup survival analysis, nuclear PRMT5-positive/IL-6-positive group had worst survival, whereas nuclear PRMT5-negative/IL-6-negative group had the best survival. Similarly, patients with p16-negative/nuclear PRMT5-positive tumors had worse survival compared to patients with p16-positive/nuclear PRMT5-negative tumors. Our mechanistic results suggest that IL-6 promotes nuclear translocation of PRMT5. Taken together, our results demonstrate for the first time that nuclear PRMT5 expression is associated with poor clinical outcome in OPSCC patients and IL-6 plays a role in the nuclear translocation of PRMT5. PMID:28107179

  12. Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status.

    PubMed

    Kumar, Bhavna; Yadav, Arti; Brown, Nicole V; Zhao, Songzhu; Cipolla, Michael J; Wakely, Paul E; Schmitt, Alessandra C; Baiocchi, Robert A; Teknos, Theodoros N; Old, Matthew; Kumar, Pawan

    2017-01-17

    Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. Our results show that nuclear PRMT5 was associated with poor overall survival (p < 0.012) and these patients had 1.732 times higher hazard of death (95% CI: 1.127-2.661) as compared to patients in whom PRMT5 was not present in the nucleus of the tumors. Nuclear PRMT5 expression was inversely correlated with p16-status (p < 0.001) and was significantly higher in tumor samples from patients who smoked > 10 pack-years (p = 0.013). In addition, nuclear PRMT5 was directly correlated with cyclin D1 (p = 0.0101) and IL-6 expression (p < 0.001). In a subgroup survival analysis, nuclear PRMT5-positive/IL-6-positive group had worst survival, whereas nuclear PRMT5-negative/IL-6-negative group had the best survival. Similarly, patients with p16-negative/nuclear PRMT5-positive tumors had worse survival compared to patients with p16-positive/nuclear PRMT5-negative tumors. Our mechanistic results suggest that IL-6 promotes nuclear translocation of PRMT5. Taken together, our results demonstrate for the first time that nuclear PRMT5 expression is associated with poor clinical outcome in OPSCC patients and IL-6 plays a role in the nuclear translocation of PRMT5.

  13. A novel mutation in CRYAB associated with autosomal dominant congenital nuclear cataract in a Chinese family

    PubMed Central

    Chen, Qiang; Ma, Junjie; Yan, Ming; Mothobi, Maneo Emily; Liu, Yuanyuan

    2009-01-01

    Purpose To identify the genetic defects associated with autosomal dominant congenital nuclear cataract in a Chinese family. Methods Clinical data were collected, and the phenotypes of the affected members in this family were recorded by slit-lamp photography. Genomic DNA was isolated from peripheral blood. Mutations were screened in cataract-associated candidate genes through polymerase chain reaction (PCR) analyses and sequencing. Structural models of the wild-type and mutant αB-crystallin were generated and analyzed by SWISS-MODEL. Results Mutation screening identified only one heterozygous G→A transition at nucleotide 32 in the first exon of αB-crystallin (CRYAB), resulting in an amino acid change from arginine to histidine at codon 11 (R11H). This mutation segregated in all available affected family members but was not observed in any of the unaffected persons of the family. The putative mutation disrupted a restriction site for the enzyme, Fnu4HI, in the affected family members. The disruption, however, was not found in any of the randomly selected ophthalmologically normal individuals or in 40 unrelated senile cataract patients. Computer-assisted prediction suggested that this mutation affected the biochemical properties as well as the structure of αB-crystallin. Conclusions These results supported the idea that the novel R11H mutation was responsible for the autosomal dominant nuclear congenital cataract in this pedigree. PMID:19597569

  14. Nuclear Expression of the Deubiquitinase CYLD Is Associated with Improved Survival in Human Hepatocellular Carcinoma

    PubMed Central

    Welte, Stefan; Urbanik, Toni; Elßner, Christin; Kautz, Nicole; Koehler, Bruno Christian; Waldburger, Nina; Bermejo, Justo Lorenzo; Pinna, Federico; Weiss, Karl-Heinz; Schemmer, Peter; Jaeger, Dirk; Longerich, Thomas; Breuhahn, Kai; Schulze-Bergkamen, Henning

    2014-01-01

    Background & Aims The deubiquitinase CYLD removes (K-63)-linked polyubiquitin chains from proteins involved in NF-κB, Wnt/ß-catenin and Bcl-3 signaling. Reduced CYLD expression has been reported in different tumor entities, including hepatocellular carcinoma (HCC). Furthermore, loss of CYLD has been shown to contribute to HCC development in knockout animal models. This study aimed to assess subcellular CYLD expression in tumor tissues and its prognostic significance in HCC patients undergoing liver resection or liver transplantation. Methods Subcellular localization of CYLD was assessed by immunohistochemistry in tumor tissues of 95 HCC patients undergoing liver resection or transplantation. Positive nuclear CYLD staining was defined as an immunhistochemical (IHC) score ≥3. Positive cytoplasmic CYLD staining was defined as an IHC score ≥6. The relationship with clinicopathological parameters was investigated. Cell culture experiments were performed to analyze subcellular CYLD expression in vitro. Results Cytoplasmic CYLD expression was observed in 57 out of 95 (60%) HCC specimens (cyt°CYLD+). Nuclear CYLD staining was positive in 52 out of 95 specimens (55%, nucCYLD+). 13 out of 52 nucCYLD+ patients (25%) showed a lack of cytoplasmic CYLD expression. nucCYLD+ was associated with prolonged overall survival in patients after resection or liver transplantation (P = 0.007). 5-year overall survival rates were 63% in nucCYLD+ vs. 26% in nucCYLD- patients. Nuclear CYLD staining strongly correlated with tumor grading (P<0.001) and Ki67 positivity (P = 0.005). nucCYLD+ did not prove to be an independent prognostic parameter. In vitro, Huh7, Hep3B and HepG2 showed reduced CYLD levels compared to the non-malignant liver cell line THLE-2. Induction of CYLD expression by doxorubicin treatment led to increased cytoplasmic and nuclear expression of CYLD. Conclusions Expression of nuclear CYLD is a novel prognostic factor for improved survival in patients with HCC

  15. Close but Distinct Regions of Human Herpesvirus 8 Latency-Associated Nuclear Antigen 1 Are Responsible for Nuclear Targeting and Binding to Human Mitotic Chromosomes

    PubMed Central

    Piolot, Tristan; Tramier, Marc; Coppey, Maité; Nicolas, Jean-Claude; Marechal, Vincent

    2001-01-01

    Human herpesvirus 8 is associated with all forms of Kaposi's sarcoma, AIDS-associated body cavity-based lymphomas, and some forms of multicentric Castleman's disease. Herpesvirus 8, like other gammaherpesviruses, can establish a latent infection in which viral genomes are stably maintained as multiple episomes. The latent nuclear antigen (LANA or LNAI) may play an essential role in the stable maintenance of latent episomes, notably by interacting concomitantly with the viral genomes and the metaphase chromosomes, thus ensuring an efficient transmission of the neoduplicated episomes to the daughter cells. To identify the regions responsible for its nuclear and subnuclear localization in interphase and mitotic cells, LNAI and various truncated forms were fused to a variant of green fluorescent protein. This enabled their localization and chromosome binding activity to be studied by low-light-level fluorescence microscopy in living HeLa cells. The results demonstrate that nuclear localization of LNAI is due to a unique signal, which maps between amino acids 24 and 30. Interestingly, this nuclear localization signal closely resembles those identified in EBNA1 from Epstein-Barr virus and herpesvirus papio. A region encompassing amino acids 5 to 22 was further proved to mediate the specific interaction of LNA1 with chromatin during interphase and the chromosomes during mitosis. The presence of putative phosphorylation sites in the chromosome binding sites of LNA1 and EBNA1 suggests that their activity may be regulated by specific cellular kinases. PMID:11264383

  16. Self-association of cromolyn sodium in aqueous solution characterized by nuclear magnetic resonance spectroscopy.

    PubMed

    Ding, Xuan; Stringfellow, Thomas C; Robinson, Joseph R

    2004-05-01

    The major objective of this study was to investigate and characterize the solution properties of cromolyn sodium (in D(2)O or D(2)O/H(2)O phosphate buffer at pH 7.5) using nuclear magnetic resonance (NMR) spectroscopy. The self-association of cromolyn molecules was examined primarily via one-dimensional (1)H and (13)C, and two-dimensional homonuclear NOESY NMR. Significant spectral shifts were observed for a majority of cromolyn (1)H and (13)C resonances, and are attributed to inter-molecular ring-stacking association accompanied by intra-molecular conformational changes. The critical self-association concentration was determined to be 10 mg/mL at pH 7.5 and 25 degrees C by measuring the chemical shift of a specific cromolyn (1)H resonance. The observed magnitude and sign changes of NOESY correlations indicate the formation of cromolyn aggregates with restricted molecular mobility. Mesomorphic liquid crystal formation is suggested by uniformly pronounced line broadening in concentrated cromolyn solutions; the transition concentration was approximately 60 mg/mL at 25 degrees C, which is consistent with literature findings based on other techniques. A stronger tendency toward association was observed at lower temperature but aggregation appeared to be independent of pH. Lastly, it was concluded that self-association of cromolyn is promoted by the presence of monovalent cations as a result of reduced electrostatic repulsive forces.

  17. Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus.

    PubMed

    Jeong, Joseph H; Orvis, Joshua; Kim, Jong Wook; McMurtrey, Curtis P; Renne, Rolf; Dittmer, Dirk P

    2004-04-16

    Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 has been established as the etiological agent of Kaposi's sarcoma and certain AIDS-associated lymphomas. KSHV establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (LANA) protein. LANA is necessary and sufficient to maintain the KSHV episome. It also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ability to bind to the p53 and pRb tumor suppressor proteins. Previously, we identified the LANA promoter (LANAp) and showed that it was positively regulated by LANA itself. Here, we present a detailed mutational analysis and define cis-acting elements and trans-acting factors for the core LANAp. We found that a downstream promoter element, TATA box, and GC box/Sp1 site at -29 are all individually required for activity. This architecture places LANAp into the small and unusual group of eukaryotic promoters that contain both the downstream promoter element and TATA element but lack a defined initiation site. Furthermore, we demonstrate that LANA regulates its own promoter via its C-terminal domain and does bind to a defined site within the core promoter.

  18. Dr. David Sawyer, Mickey Mouse and Dr. David Brown attend a ceremony at Ronald McNair Middle School

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. David Sawyer (left), Superintendent of the Brevard County School District, Mickey Mouse, and Dr. David Brown, a NASA astronaut, attend a tribute to NASA astronaut Ronald McNair held in the gymnasium of Ronald McNair Magnet School in Cocoa, Fla. During the tribute, Walt Disney World presented a portrait of McNair to the school, which had previously been renamed for the fallen astronaut. McNair was one of a crew of seven who lost their lives during an accident following launch of the Space Shuttle Challenger in January 1986.

  19. Dr. David Sawyer, Mickey Mouse and Dr. David Brown attend a ceremony at Ronald McNair Middle School

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. David Sawyer (left), Superintendent of the Brevard County School District, Mickey Mouse, and Dr. David Brown, a NASA astronaut, attend a tribute to NASA astronaut Ronald McNair held in the gymnasium of Ronald McNair Magnet School in Cocoa, Fla. During the tribute, Walt Disney World presented a portrait of McNair to the school, which had previously been renamed for the fallen astronaut. McNair was one of a crew of seven who lost their lives during an accident following launch of the Space Shuttle Challenger in January 1986.

  20. Yes-Associated Protein (YAP) Promotes the Nuclear Import of p73

    NASA Astrophysics Data System (ADS)

    Zhang, Heng; Wu, Shengnan

    2011-01-01

    p73 has been identified as a structural and functional homolog of the tumor suppressor p53. However, mechanisms that regulate the localization of p73 have not been fully clarified. The Yes-associated protein (YAP) is a transcriptional coactivator. As a transcriptional coactivator, YAP needs to bind transcription factors to stimulate gene expression. p73 is a reported YAP target transcription factors and YAP has been shown to positively regulate p73 in promoting apoptosis. Previous studies show that p73 interacts with YAP through its PPPY motif, and increases p73 transactivation of apoptotic genes. In this study, we focused on YAP's regulation of the localization of p73. After transient transfection into Rat pheochromocytoma (PC12) cells and Human embryonic kidney 293T cells with GFP-YAP and/or YFP-p73, and incubated for 24 hours expression. p73 was fused to YFP to allow the examination of its subcellular localization. When expressed alone, YFP-p73 was distributed throughout the cell. When coexpressed with YAP, nuclear accumulation of YFP-p73 became evident. We quantitated the effect of YAP on the redistribution of YFP-p73 by counting cells with nuclear-only YFP signal. We found that YAP can influence the subcellular distribution of p73. Altogether, coexpression with YAP affected the subcellular distribution of the p73 protein. Our studies attribute a central role to YAP in regulating p73 accumulation and YAP, at least in part, might promote the nuclear import of p73.

  1. Americium and plutonium association with magnesium hydroxide colloids in alkaline nuclear industry process environments

    NASA Astrophysics Data System (ADS)

    Maher, Zoe; Ivanov, Peter; O'Brien, Luke; Sims, Howard; Taylor, Robin J.; Heath, Sarah L.; Livens, Francis R.; Goddard, David; Kellet, Simon; Rand, Peter; Bryan, Nick D.

    2016-01-01

    The behaviours of Pu, Am and colloids in feed solutions to the Site Ion-exchange Effluent Plant (SIXEP) at the Sellafield nuclear reprocessing site in the U.K. have been studied. For both Pu and Am, fractions were found to be associated with material in the colloidal size range, with ˜50% of the Pu in the range 1-200 nm. The concentration of soluble Pu (<1 nm) was ˜1 nM, which is very similar to the solubility limit for Pu(V). The soluble Am concentration was of the order of 10-11 M, which was below the solubility limit of americium hydroxide. The size, morphology and elemental composition of the particulates and colloids in the feed solutions were investigated. Magnesium is homogeneously distributed throughout the particles, whereas U, Si, Fe, and Ca were present in localised areas only. Amongst some heterogeneous material, particles were identified that were consistent with hydrotalcite. The distribution of 241Am(III) on brucite (magnesium hydroxide) colloids of different sizes was studied under alkaline conditions representative of nuclear fuel storage pond and effluent feed solution conditions. The morphology of the brucite particles in the bulk material observed by ESEM was predominantly hexagonal, while that of the carbonated brucite consisted of hexagonal species mixed with platelets. The association of 241Am(III) with the brucite colloids was studied by ultrafiltration coupled with gamma ray-spectrometry. For carbonate concentrations up to 10-3 M, the 241Am(III) was mainly associated with larger colloids (>300 kDa), and there was a shift from the smaller size fractions to the larger over a period of 6 months. At higher carbonate concentrations (10-2 M), the Am was predominantly detected in the true solution fraction (<3 kDa) and in smaller size colloidal fractions, in the range 3-100 kDa.

  2. Chicken histone genes retain nuclear matrix association throughout the cell cycle.

    PubMed Central

    Dalton, S; Younghusband, H B; Wells, J R

    1986-01-01

    The association between histone genes and the nuclear matrix (NM) during periods of high (S-phase) and low (non-S-phase) transcriptional activity has been investigated with synchronized cells from a chicken erythroid cell line (abbreviated ts34). By DNase I and restriction enzyme analysis, these studies reveal that both core and linker histone genes (represented by H2A and H1 genes respectively) are attached to the NM independent of their transcriptional activity during the cell-cycle. The tissue-specific histone gene H5, expressed constitutively, is nuclear matrix (NM)-associated in ts34 cells but is found in the supernatant (S/N) fractions of a non-erythroid T-cell line. Furthermore, we show that DNA sequences necessary for NM-attachment of the H5 gene lie within a 780 base pair region spanning part of the coding and 5' non-translated region. Of the three non-histone genes investigated, beta-actin sequences are expressed and are NM-attached, feather keratin genes are not expressed and predominate in the S/N, and beta-globin genes although not expressed in the ts34 cell line used were found in the NM fraction. In this case the association may be fortuitous or may reflect an early event prior to transcription of globin genes in differentiating erythroid cells. These results generally support the notion that actively transcribed genes are NM-attached, but that attachment per se is not synonymous with transcription. Images PMID:2428014

  3. JPRS Report, Nuclear Developments

    DTIC Science & Technology

    1988-04-01

    Sir David Ford, to appoint concerns. a professional from among their ranks to oversee local Among the 23- year old federation’s members are the...down this afternoon following an explosion and a fire. Official This class of submarine is about 20 years old , which in sources said the explosion...Frankfurt/Main FRANKFURTER R UNDSCHA U, 23, 25 Jan 88] .............................. 12 BW To Halt Future Nuclear Plants, Explore Alternative Energy

  4. Q & A with Ed Tech Leaders: Interview with David Dockterman

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.

    2014-01-01

    In this article, Michael F. Shaughnessy, Contributing Editor of this journal, interviews David Dockterman, Chief Architect, Learning Sciences, at Scholastic Education, where he provides guidance on turning research into practical programs. Dockterman was one of the founders of Tom Snyder Productions, a leading educational software developer and…

  5. Global Education: Scope and Directions. An Interview with David Selby.

    ERIC Educational Resources Information Center

    Steinback, Sylvia; Rathenow, Hanns-Fred

    1987-01-01

    David Selby, Director of the Centre for Global Education at York University (United Kingdom), responds to questions about the history of global education; the different approaches taken in the United Kingdom and the United States; the central concepts of a global perspective in the curriculum; and the most appropriate teaching approaches. (LS)

  6. Video from Panel Discussion with Joseph Fraumeni and David Schottenfeld

    Cancer.gov

    Video footage from Panel Discussion with Joseph Fraumeni and David Schottenfeld on Cancer Epidemiology over the Last Half-Century and Thoughts on the Future. The discussion took place on May 11, 2012, when DCEG hosted Dr. Schottenfeld as a Visiting Scholar.

  7. David Hoffman's Law School Lectures, 1822-1833.

    ERIC Educational Resources Information Center

    Shaffer, Thomas L.

    1982-01-01

    The Baltimore lawyer David Hoffman (1784-1854), the father of American legal ethics, was also the first of the systematic American legal educators. The history and operation of his law school, the curriculum, and his effective use of the lecture method are described and discussed. (MSE)

  8. Moral philosophers are moral experts! A reply to David Archard.

    PubMed

    Gordon, John-Stewart

    2014-05-01

    In his article 'Why Moral Philosophers Are Not and Should Not Be Moral Experts' David Archard attempts to show that his argument from common-sense morality is more convincing than other competing arguments in the debate. I examine his main line of argumentation and eventually refute his main argument in my reply.

  9. Astronaut David Wolf in medical experiment in SLS-2

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Astronaut David A. Wolf, mission specialist, participates in an experiment that investigates in-space distribution and movement of blood and gas in the pulmonary system. The data gathered during the two-week flight will be compared with results of tests performed on Earth to determine the changes that occur in pulmonary functions.

  10. From the Ocean's Flotsam, David Wiesner Imagines a Journey

    ERIC Educational Resources Information Center

    Ward, Barbara A.

    2008-01-01

    David Wiesner's 2007 Caldecott Medal-winning "Flotsam" blends the events of everyday life with the surreal. As he often does in his picture books, Wiesner plays with size and scale, opening "Flotsam" with a full-page illustration of a sand crab and the enormous eye behind it before pulling back on the second page to reveal the creature's actual…

  11. STS-69 Mission Commander David M. Walker in white room

    NASA Technical Reports Server (NTRS)

    1995-01-01

    STS-69 Mission Commander David M. Walker chats with white room closeout crew members Bob Saulnier (left), Regulo Villalobos and closeout crew leader Travis Thompson prior to entering the flight deck of the Space Shuttle Endeavour at Launch Pad 39A.

  12. Reflections on the Scholarly Contributions of Professor David H. Jonassen

    ERIC Educational Resources Information Center

    Reeves, Thomas C.; Lee, Chwee Beng; Hung, Woei

    2013-01-01

    The six papers in this special issue of "Computers and Education" honoring Professor David H. Jonassen are diverse in nature. They also reflect differing interpretations of the implications of Jonassen's work for research and development focused on instructional models and the factors influencing instruction as well as the directions for future…

  13. Astronaut David Scott practicing for Gemini 8 EVA

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Astronaut David R. Scott practicing for Gemini 8 extravehicular acitivity (EVA) in bldg 4 of the Manned Spacecraft Center on the air bearing floor. He is wearing the the Hand-Held Maneuvering Unit which he will use during the EVA.

  14. David E. Smith Receives 2012 Charles A. Whitten Medal: Citation

    NASA Astrophysics Data System (ADS)

    Phillips, Roger J.

    2013-01-01

    David E. Smith was awarded the 2012 Charles A. Whitten Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is for "outstanding achievement in research on the form and dynamics of the Earth and planets."

  15. Child Welfare Research and Training: A Response to David Stoesz

    ERIC Educational Resources Information Center

    Smith, Brenda D.; Vandiver, Vikki L.

    2016-01-01

    In this response to David Stoesz' critique, "The Child Welfare Cartel," the authors agree that child welfare research and training must be improved. The authors disagree, however, with Stoesz' critique of social work education, his assessment of the most-needed forms of child welfare research, and his depiction of the goals and…

  16. From the Ocean's Flotsam, David Wiesner Imagines a Journey

    ERIC Educational Resources Information Center

    Ward, Barbara A.

    2008-01-01

    David Wiesner's 2007 Caldecott Medal-winning "Flotsam" blends the events of everyday life with the surreal. As he often does in his picture books, Wiesner plays with size and scale, opening "Flotsam" with a full-page illustration of a sand crab and the enormous eye behind it before pulling back on the second page to reveal the creature's actual…

  17. Child Welfare Research and Training: A Response to David Stoesz

    ERIC Educational Resources Information Center

    Smith, Brenda D.; Vandiver, Vikki L.

    2016-01-01

    In this response to David Stoesz' critique, "The Child Welfare Cartel," the authors agree that child welfare research and training must be improved. The authors disagree, however, with Stoesz' critique of social work education, his assessment of the most-needed forms of child welfare research, and his depiction of the goals and…

  18. David Reeder and the History of Urban Education

    ERIC Educational Resources Information Center

    Marsden, Bill; Grosvenor, Ian

    2007-01-01

    David Reeder was one of the most important conservers of the traditions of urban history scholarship established during the 1960s at the University of Leicester under the leadership of Professor H. J. Dyos. Among Reeder's major achievements were the application of the skills and objectives of such scholarship to the history of education, and in…

  19. Grade 1 Students Meet David Wiesner's "Three Pigs."

    ERIC Educational Resources Information Center

    Pantaleo, Sylvia

    2002-01-01

    Describes the oral, written, and visual arts responses of a group of Grade 1 children. Discusses first grade children's understandings of and responses to several Radical Change characteristics and metafictive techniques found in David Wiesner's "The Three Pigs" (2001), the 2002 Randolph Caldecott Medal winner. Explores the nature of the…

  20. Empowering Adolescent Readers: Intertextuality in Three Novels by David Almond

    ERIC Educational Resources Information Center

    Latham, Don

    2008-01-01

    In "Skellig," "Kit's Wilderness," and "Clay", David Almond employs various types of intertextuality to enrich his narratives. Through the use of allusion, adaptation, collage, and mise-en-abyme, he encourages his adolescent readers to seek out precursor texts and to consider the interrelationships between these texts and his own. By so doing, he…

  1. David Almond's "Skellig": "A New Vista of Contemplation"?

    ERIC Educational Resources Information Center

    Stewart, Susan Louise

    2009-01-01

    The debates that have arisen regarding Darwin's theories of evolution and Christian views of creation and their place in education in the United States have frequently been extremely heated, resulting in trials, hearings, and laws. This article provides an overview of some of the disagreements and illustrates how David Almond's British novel,…

  2. Instructional Implications of David C. Geary's Evolutionary Educational Psychology

    ERIC Educational Resources Information Center

    Sweller, John

    2008-01-01

    David C. Geary's thesis has the potential to alter our understanding of those aspects of human cognition relevant to instruction. His distinction between biologically primary knowledge that we have evolved to acquire and biologically secondary knowledge that is culturally important, taught in educational institutions and which we have not evolved…

  3. David P. McAllester on Navajo Music.

    ERIC Educational Resources Information Center

    Campbell, Patricia Shehan

    1994-01-01

    Asserts that music teachers increasingly are interested in music that originates outside the Western European tradition. Presents an interview with David P. McAllester on world music, the musical culture of the Navajo people, and how it should be taught in music classrooms. (CFR)

  4. The Sociological Foundations of David Elliott's "Music Matters" Philosophy.

    ERIC Educational Resources Information Center

    Paul, Stephen J.

    2000-01-01

    Focuses on the ideas presented in the book, "Music Matters (David Elliott)." Discusses Elliott's stance on praxialism, stating that his book is based on social mediation of action as its behavioral theory. Addresses Elliott's concept of expertise and topics using an interactionist perspective as a means of interpretation. (CMK)

  5. Can Education Save the World? A Response to David Gruenewald

    ERIC Educational Resources Information Center

    Stables, Andrew

    2004-01-01

    Any commitment to education for sustainability assumes that teaching and learning can reduce or prevent damage to the biosphere. However, such an assumption remains deeply problematic. David Gruenewald's is only one of several possible epistemological positions. This article discusses the variety of such positions, arguing for that which might…

  6. David Almond's "Skellig": "A New Vista of Contemplation"?

    ERIC Educational Resources Information Center

    Stewart, Susan Louise

    2009-01-01

    The debates that have arisen regarding Darwin's theories of evolution and Christian views of creation and their place in education in the United States have frequently been extremely heated, resulting in trials, hearings, and laws. This article provides an overview of some of the disagreements and illustrates how David Almond's British novel,…

  7. Empowering Adolescent Readers: Intertextuality in Three Novels by David Almond

    ERIC Educational Resources Information Center

    Latham, Don

    2008-01-01

    In "Skellig," "Kit's Wilderness," and "Clay", David Almond employs various types of intertextuality to enrich his narratives. Through the use of allusion, adaptation, collage, and mise-en-abyme, he encourages his adolescent readers to seek out precursor texts and to consider the interrelationships between these texts and his own. By so doing, he…

  8. Inside the Classroom of Harvard Law School Professor David Wilkins.

    ERIC Educational Resources Information Center

    Lawrence-Lightfoot, Sara

    1999-01-01

    Examines the teaching methods of David Wilkins, an African American Harvard Law School professor considered an exciting teacher by his students and colleagues. Describes his skill in getting students to attend class, engage in legal thinking, feel comfortable in the classroom, and learn the formal rituals and procedures for the court. (SM)

  9. "The Word I Would Use Is 'Aesthetic'": Reading David Hawkins.

    ERIC Educational Resources Information Center

    Featherstone, Helen; Featherstone, Joseph

    2002-01-01

    Discusses the life of David Hawkins, one of the most influential educators involved in school reform in the 1960s. Focuses on the aesthetic as the center of Hawkins' vision of schooling. Compares Hawkins' perspective to Dewey's in terms of the aesthetic. (KHR)

  10. Astronauts David Griggs and Jeff Hoffman in Egress training

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Astronaut David Griggs, wearing an extravehicular mobility unit (EMU), practices emergency egress from the space shuttle during an underwater test in the Weightless Environment Training Facility (WETF) (26473); Griggs (left) and Astronaut Jeff Hoffman train for egress in the WETF (26474).

  11. Reflections on the Freshman Year: An Interview with David Riesman.

    ERIC Educational Resources Information Center

    Gardner, John N.; Barefoot, Betsy

    1991-01-01

    An interview with David Riesman, founder of Harvard University's (Massachusetts) freshman seminar program, covers the origins and structure of the seminars, Riesman's own college experience, the importance of the college experience, faculty research, and the role of faculty in student intellectual development. (MSE)

  12. Challenging Texts: Teaching Deliberately--Reading Henry David Thoreau's "Walden"

    ERIC Educational Resources Information Center

    Davis, Andrea

    2011-01-01

    One of the more difficult 19th-century American texts for high school students to read is undoubtedly Henry David Thoreau's "Walden." His erudite allusions, often page-long sentences, and sophisticated sense of the ironic initially leave many students cold. Still, the author encourages them to read amid the din of a cultural cacophony that shouts…

  13. Henry David Thoreau and Martin Luther King, Jr. Lesson Plan.

    ERIC Educational Resources Information Center

    Powell, Brent

    1995-01-01

    Presents a five-lesson, high school instructional unit on the ideas and activities of Henry David Thoreau and Martin Luther King, Jr. Includes student objectives, step-by-step instructional procedures, and discussion questions. Provides quotations by Thoreau and King. (CFR)

  14. Chella David: a lifetime contribution in translational immunology.

    PubMed

    Gershwin, M Eric; Shoenfeld, Yehuda

    2011-09-01

    Immunology, like most scientific disciplines, is filled with buzz words. One such buzz word or term has been coined "translational immunology". Indeed, translational research is amongst the most popular expressions used to justify the use of basic research in the hopes that such research will lead to solutions to clinical problems. In fact, no such justification is needed and some of the most important observations in clinical medicine have been derived from basic science; basic science that had no idea at its time of its usefulness in clinical medicine. This special issue is devoted to Chella David. Chella's contributions in immunology have been legion. Before inbred mice became popular, long before multi-million dollar companies were developed to develop such models, Chella David was hard at the bench studying the genetics of the murine immune system and the importance of such mouse models in autoimmune diseases. Importantly, Dr. David provided animals without strings, without the burdens of MTAs, that now impede research. Chella has been generous with his time, with his reagents, and has been a caring and devoted mentor to generations of students. This issue is part of our series to recognize autoimmunologists and dedicated themes that include papers in multiple disciplines of immunology, but especially are focused on cutting-edge applications that will improve clinical therapeutics. Chella David, at age 75, is an athlete in immunology and still keeps going with the same enthusiasm as manifest as a young post-doc. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Challenging Texts: Teaching Deliberately--Reading Henry David Thoreau's "Walden"

    ERIC Educational Resources Information Center

    Davis, Andrea

    2011-01-01

    One of the more difficult 19th-century American texts for high school students to read is undoubtedly Henry David Thoreau's "Walden." His erudite allusions, often page-long sentences, and sophisticated sense of the ironic initially leave many students cold. Still, the author encourages them to read amid the din of a cultural cacophony that shouts…

  16. My Journey Into the Physics of David Finkelstein

    NASA Astrophysics Data System (ADS)

    Alexander, Stephon

    2017-01-01

    David Finkelstein was a co-pioneer of the use of topology and solitons in theoretical physics. The author reflects on the great impact Finkelstein had on his research throughout his career. The author provides an application of one of Finkelsteins idea pertaining to the fusion of quantum theory with relativity by utilizing techniques from Loop Quantum Gravity.

  17. Life after Death in Poverty: David Treuer's "Little"

    ERIC Educational Resources Information Center

    Stirrup, David

    2005-01-01

    David Treuer's debut novel, "Little" (1995), is set on a Minnesota reservation, centering around a dilapidated housing tract that its small community of residents call "Poverty." Aptly named both for the condition and background of the housing, this name is the first pointer to the type of multifaceted reading that the novel…

  18. Cara David: A Leading Woman in Australian Education.

    ERIC Educational Resources Information Center

    Kyle, Noeline J.

    1993-01-01

    In broad context of patriarchal relations, female leaders' absence from historical texts accords with sexual division of labor within society and gendered nature of teaching. Cara David, educationist, social reformer, and political activist in early twentieth-century Australia, is better known as the clever, pretty wife of a renown geologist.…

  19. Astronaut David Scott practicing for Gemini 8 EVA

    NASA Image and Video Library

    1966-02-01

    S66-19284 (1 Feb. 1966) --- Astronaut David R. Scott practicing for Gemini-8 extravehicular activity (EVA) in building 4 of the Manned Spacecraft Center on the air bearing floor. He is wearing the Hand-Held Maneuvering Unit which he will use during the EVA. Photo credit: NASA

  20. Report of the Secretary of Defense Task Force on DoD Nuclear Weapons Management. Phase II: Review of the DoD Nuclear Mission

    DTIC Science & Technology

    2008-12-01

    8 William Broad and David Sanger , “Restraints Fray and Risks Grow as Nuclear Club Gains Members,” New York...Broad, William and David Sanger . “Restraints Fray and Risks Grow as Nuclear Club Gains Members,” New York Times, Oct. 15, 2006. Brown, Harold. “New...Area Secretary of Defense Task Force on DoD Nuclear Weapons Management Director of Analysis Mrs. Margaret R. Munson Executive Fellow

  1. Changes in mitochondrial DNA alter expression of nuclear encoded genes associated with tumorigenesis

    SciTech Connect

    Jandova, Jana; Janda, Jaroslav; Sligh, James E

    2012-10-15

    We previously reported the presence of a mtDNA mutation hotspot in UV-induced premalignant and malignant skin tumors in hairless mice. We have modeled this change (9821insA) in murine cybrid cells and demonstrated that this alteration in mtDNA associated with mtBALB haplotype can alter the biochemical characteristics of cybrids and subsequently can contribute to significant changes in their behavioral capabilities. This study shows that changes in mtDNA can produce differences in expression levels of specific nuclear-encoded genes, which are capable of triggering the phenotypes such as seen in malignant cells. From a potential list of differentially expressed genes discovered by microarray analysis, we selected MMP-9 and Col1a1 for further studies. Real-time PCR confirmed up-regulation of MMP-9 and down-regulation of Col1a1 in cybrids harboring the mtDNA associated with the skin tumors. These cybrids also showed significantly increased migration and invasion abilities compared to wild type. The non-specific MMP inhibitor, GM6001, was able to inhibit migratory and invasive abilities of the 9821insA cybrids confirming a critical role of MMPs in cellular motility. Nuclear factor-{kappa}B (NF-{kappa}B) is a key transcription factor for production of MMPs. An inhibitor of NF-{kappa}B activation, Bay 11-7082, was able to inhibit the expression of MMP-9 and ultimately decrease migration and invasion of mutant cybrids containing 9821insA. These studies confirm a role of NF-{kappa}B in the regulation of MMP-9 expression and through this regulation modulates the migratory and invasive capabilities of cybrids with mutant mtDNA. Enhanced migration and invasion abilities caused by up-regulated MMP-9 may contribute to the tumorigenic phenotypic characteristics of mutant cybrids. -- Highlights: Black-Right-Pointing-Pointer Cybrids are useful models to study the role of mtDNA changes in cancer development. Black-Right-Pointing-Pointer mtDNA changes affect the expression of nuclear

  2. A horizontally transferred nuclear gene is associated with microhabitat variation in a natural plant population

    PubMed Central

    Tunlid, Anders; Ghatnekar, Lena

    2015-01-01

    Horizontal gene transfer involves the non-sexual interspecific transmission of genetic material. Even if they are initially functional, horizontally transferred genes are expected to deteriorate into non-expressed pseudogenes, unless they become adaptively relevant in the recipient organism. However, little is known about the distributions of natural transgenes within wild species or the adaptive significance of natural transgenes within wild populations. Here, we examine the distribution of a natural plant-to-plant nuclear transgene in relation to environmental variation within a wild population. Festuca ovina is polymorphic for an extra (second) expressed copy of the nuclear gene (PgiC) encoding cytosolic phosphoglucose isomerase, with the extra PgiC locus having been acquired horizontally from the distantly related grass genus Poa. We investigated variation at PgiC in samples of F. ovina from a fine-scale, repeating patchwork of grassland microhabitats, replicated within spatially separated sites. Even after accounting for spatial effects, the distributions of F. ovina individuals carrying the additional PgiC locus, and one of the enzyme products encoded by the locus, are significantly associated with fine-scale habitat variation. Our results suggest that the PgiC transgene contributes, together with the unlinked ‘native’ PgiC locus, to local adaptation to a fine-scale mosaic of edaphic and biotic grassland microhabitats. PMID:26674953

  3. A horizontally transferred nuclear gene is associated with microhabitat variation in a natural plant population.

    PubMed

    Prentice, Honor C; Li, Yuan; Lönn, Mikael; Tunlid, Anders; Ghatnekar, Lena

    2015-12-22

    Horizontal gene transfer involves the non-sexual interspecific transmission of genetic material. Even if they are initially functional, horizontally transferred genes are expected to deteriorate into non-expressed pseudogenes, unless they become adaptively relevant in the recipient organism. However, little is known about the distributions of natural transgenes within wild species or the adaptive significance of natural transgenes within wild populations. Here, we examine the distribution of a natural plant-to-plant nuclear transgene in relation to environmental variation within a wild population. Festuca ovina is polymorphic for an extra (second) expressed copy of the nuclear gene (PgiC) encoding cytosolic phosphoglucose isomerase, with the extra PgiC locus having been acquired horizontally from the distantly related grass genus Poa. We investigated variation at PgiC in samples of F. ovina from a fine-scale, repeating patchwork of grassland microhabitats, replicated within spatially separated sites. Even after accounting for spatial effects, the distributions of F. ovina individuals carrying the additional PgiC locus, and one of the enzyme products encoded by the locus, are significantly associated with fine-scale habitat variation. Our results suggest that the PgiC transgene contributes, together with the unlinked 'native' PgiC locus, to local adaptation to a fine-scale mosaic of edaphic and biotic grassland microhabitats.

  4. Two affected siblings with nuclear cataract associated with a novel missense mutation in the CRYGD gene.

    PubMed

    Messina-Baas, Olga Maud; Gonzalez-Huerta, Luz Maria; Cuevas-Covarrubias, Sergio Alberto

    2006-08-24

    To identify the disease locus for nuclear congenital cataract in a nonconsanguineous family with two affected members. One family with two affected members with congenital cataract and 170 normal controls were examined. DNA from leukocytes and bucal swabs was isolated to analyze the CRYGA-D cluster genes and microsatellite markers D2S325, D2S2382, and D2S126, and to discard paternity through gene scan with several highly polymorphic markers. DNA sequencing analysis of the CRYGA-D cluster genes of the two affected members showed a novel heterozygous missense mutation c.320A > C within exon 3 of the CRYGD gene. This transversion mutation resulted in the substitution of glutamic acid 107 by an alanine (E107A). Analysis of the two unaffected members of the family and the normal parents showed a normal sequence of the CRYGA-D cluster genes. This mutation was not found in a group of 170 unrelated controls. We consider that it is unlikely that this abnormal allele represents a rare polymorphism. DNA analysis showed no evidence for non-paternity while genotyping indicated that the haplotype of the mother co-segregated with the disease. In this study we describe the mutation c.320A > C (E107A) in the CRYGD gene associated with nuclear congenital cataract. Haplotype analysis strongly suggests that the origin of the mutation was transmitted through the mother.

  5. Human GTPases associate with RNA polymerase II to mediate its nuclear import.

    PubMed

    Carré, Clément; Shiekhattar, Ramin

    2011-10-01

    Small GTPases share a biochemical mechanism and act as binary molecular switches. One important function of small GTPases in the cell is nucleocytoplasmic transport of both proteins and RNA. Here, we show the stable association of human GPN1 and GPN3, small GTPases related to Ran, with RNA polymerase II (RNAPII) isolated from either the cytoplasmic or nuclear fraction. GPN1 and GPN3 directly interact with RNAPII subunit 7 (RPB7)/RPB4 and the C-terminal domain (CTD) of RNAPII. Depletion of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.

  6. The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression

    PubMed Central

    Schneider, Maren; Hellerschmied, Doris; Schubert, Tobias; Amlacher, Stefan; Vinayachandran, Vinesh; Reja, Rohit; Pugh, B. Franklin; Clausen, Tim; Köhler, Alwin

    2015-01-01

    Summary Nuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription, and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with the Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent at specific genes. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing. Our data provide mechanistic insight into how an NPC-associated adaptor complex accesses the core transcription machinery. PMID:26317468

  7. A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family

    PubMed Central

    Jin, Chongfei; Zhu, Ning; Wang, Wei; Wu, Renyi; Jiang, Jin; Shentu, Xingchao

    2008-01-01

    Purpose To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. Methods Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structural models of the wild type and mutant γC-crystallin were generated and analyzed by SWISS-MODEL. Results Sequencing of the coding regions of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the substitution of a wild type cysteine to a nonsense codon (C109X). One and a half Greek key motifs at the COOH-terminus were found to be absent in the structural model of the mutant truncated γC-crystallin. Conclusions A novel nonsense mutation in CRYGC was detected in a Chinese family with consistent autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype. PMID:18618005

  8. A general nuclear magnetic resonance analysis of hetero-association of aromatic molecules in aqueous solution

    NASA Astrophysics Data System (ADS)

    Veselkov, Alexei N.; Evstigneev, Maxim P.; Veselkov, Dennis A.; Davies, David B.

    2001-08-01

    A general nuclear magnetic resonance analysis of a statistical-thermodynamical model of hetero-association of aromatic molecules in solution has been developed to take "edge effects" into consideration, i.e., the dependence of proton chemical shifts on the position of the molecule situated inside or at the edge of the aggregate. This generalized approach is compared with a previously published model, where an average contribution to proton shielding is considered irrespective of the position of the molecule in the stack. Association parameters have been determined from experimental concentration and temperature dependences of 500 MHz proton chemical shifts of the hetero-association of the acridine dye, proflavine, and the phenanthridinium dye, ethidium bromide, in aqueous solution. Differences in the parameters in the range 10%-30% calculated using the basic and generalized approaches have been found to depend substantially on the magnitude of the equilibrium hetero-association constant Khet—the larger the value of Khet, the higher the discrepancy between the two methods.

  9. Associations between disaster exposures, peritraumatic distress, and posttraumatic stress responses in Fukushima nuclear plant workers following the 2011 nuclear accident: the Fukushima NEWS Project study.

    PubMed

    Shigemura, Jun; Tanigawa, Takeshi; Nishi, Daisuke; Matsuoka, Yutaka; Nomura, Soichiro; Yoshino, Aihide

    2014-01-01

    The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst nuclear disaster since Chernobyl. The nearby Daini plant also experienced substantial damage but remained intact. Workers for the both plants experienced multiple stressors as disaster victims and workers, as well as the criticism from the public due to their company's post-disaster management. Little is known about the psychological pathway mechanism from nuclear disaster exposures, distress during and immediately after the event (peritraumatic distress; PD), to posttraumatic stress responses (PTSR). A self-report questionnaire was administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2-3 months post-disaster (total response rate: 80.2%). The socio-demographic characteristics and disaster-related experiences were assessed as independent variables. PD and PTSR were measured by the Japanese versions of Peritraumatic Distress Inventory and the Impact of Event Scale-Revised, respectively. The analysis was conducted separately for the two groups. Bivariate regression analyses were performed to assess the relationships between independent variables, PD, and PTSR. Significant variables were subsequently entered in the multiple regression analyses to explore the pathway mechanism for development of PTSR. For both groups, PTSR highly associated with PD (Daiichi: adjusted β, 0.66; p<0.001; vs. Daini: adjusted β, 0.67; p<0.001). PTSR also associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs. Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely to be associated with PD than PTSR. Among the Fukushima nuclear plant workers, disaster exposures associated with PD. PTSR was highly affected by PD along with discrimination/slurs experience.

  10. Associations between Disaster Exposures, Peritraumatic Distress, and Posttraumatic Stress Responses in Fukushima Nuclear Plant Workers following the 2011 Nuclear Accident: The Fukushima NEWS Project Study

    PubMed Central

    Shigemura, Jun; Tanigawa, Takeshi; Nishi, Daisuke; Matsuoka, Yutaka; Nomura, Soichiro; Yoshino, Aihide

    2014-01-01

    Background The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst nuclear disaster since Chernobyl. The nearby Daini plant also experienced substantial damage but remained intact. Workers for the both plants experienced multiple stressors as disaster victims and workers, as well as the criticism from the public due to their company's post-disaster management. Little is known about the psychological pathway mechanism from nuclear disaster exposures, distress during and immediately after the event (peritraumatic distress; PD), to posttraumatic stress responses (PTSR). Methods A self-report questionnaire was administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2–3 months post-disaster (total response rate: 80.2%). The socio-demographic characteristics and disaster-related experiences were assessed as independent variables. PD and PTSR were measured by the Japanese versions of Peritraumatic Distress Inventory and the Impact of Event Scale-Revised, respectively. The analysis was conducted separately for the two groups. Bivariate regression analyses were performed to assess the relationships between independent variables, PD, and PTSR. Significant variables were subsequently entered in the multiple regression analyses to explore the pathway mechanism for development of PTSR. Results For both groups, PTSR highly associated with PD (Daiichi: adjusted β, 0.66; p<0.001; vs. Daini: adjusted β, 0.67; p<0.001). PTSR also associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs. Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely to be associated with PD than PTSR. Conclusion Among the Fukushima nuclear plant workers, disaster exposures associated with PD. PTSR was highly affected by PD along with discrimination/slurs experience. PMID:24586278

  11. Characterization of 3'----5' exonuclease associated with DNA polymerase of silkworm nuclear polyhedrosis virus.

    PubMed Central

    Mikhailov, V S; Marlyev, K A; Ataeva, J O; Kullyev, P K; Atrazhev, A M

    1986-01-01

    3'----5' Exonuclease specific for single-stranded DNA copurified with DNA polymerase of nuclear polyhedrosis virus of silkworm Bombyx mori (BmNPV Pol). BmNPV Pol has no detectable 5'----3' exonuclease activity on single-stranded or duplex DNA. Analysis of the products of 3'----5' exonucleolytic reaction showed that deoxynucleoside monophosphates were released during the hydrolysis of single-stranded DNA. The exonuclease activity cosedimented with the polymerase activity during ultracentrifugation of BmNPV Pol in glycerol gradient. The polymerase and the exonuclease activities of BmNPV Pol were inactivated by heat with nearly identical kinetics. The mode of the hydrolysis of single-stranded DNA by BmNPV Pol-associated exonuclease was strictly distributive. The enzyme dissociated from single-stranded DNA after the release of a single dNMP and then reassociated with a next polynucleotide being degradated. Images PMID:3012482

  12. Current research in nuclear medicine and molecular imaging in Italy: highlights of the 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging.

    PubMed

    Cuocolo, A

    2011-06-01

    The 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN) took place in Rimini on March 18-21, 2011 under the chairmanship of Professor Stefano Fanti. The program was of excellent quality and put a further step for the settlement of the standardized AIMN congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success with more than 1100 total participants and more than 360 abstracts received. Of these, 40 abstracts were accepted for oral and 285 for poster presentations. The original investigations presented were related to different areas of nuclear medicine and molecular imaging, with particular focus on advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in well established areas of clinical application, such as oncology, cardiology, neurology, psychiatry, endocrinology, paediatrics, and infection and inflammation. Noteworthy, several presentations at this congress, focusing on quantitative interpretation of the imaging data and on pragmatic endpoints, such as adverse outcomes, identified when nuclear medicine procedures achieved clinical effectiveness for patient care and patient management and further demonstrated that nuclear medicine plays a crucial role in the contemporary medical scenario. This highlights lecture is only a brief summary of the large amount of data presented and discussed, which can be found in much greater detail in the congress abstract book, published as volume 55, supplement 1 of the Q J Nucl Med Mol Imaging in April 2011.

  13. Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients.

    PubMed

    Maciejczyk, Adam; Łacko, Aleksandra; Ekiert, Marcin; Jagoda, Ewa; Wysocka, Teresa; Matkowski, Rafał; Hałoń, Agnieszka; Györffy, Balázs; Lage, Hermann; Surowiak, Paweł

    2013-04-01

    S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.

  14. Nuclear Factor kappa B (NFkB) pathway associated biomarkers in AIDS defining malignancies

    PubMed Central

    Ramos, Juan-Carlos; Sin, Sang-Hoon; Staudt, Michelle R.; Roy, Debasmita; Vahrson, Wolfgang; Dezube, Bruce J.; Harrington, William

    2011-01-01

    The Nuclear Factor kappa B (NFkB) pathway is essential for many human cancers. Therapeutics such as bortezomib (Velcade™), which interfere with nuclear factor NF-kappa-B(NFkB)signaling are of great clinical interest. NFkB signaling, however, is multifaceted and variable among tissues, developmental, and disease entities. Hence, targeted biomarkers of NFkB pathways are of prime importance for clinical research. We developed a novel real-time qPCR-based NFkB array. Only mechanistically validated NFkB targets were included. We then used random-forest classification to define individual genes and gene combinations within the NFkB pathways that define viral lymphoma subclasses as well as Kaposi sarcoma (KS). Few NFkB targets emerged that were universally present in all tumor types tested, underscoring the need for additional tumor-type specific biomarker discovery. (i) We uncovered tissue of origin-specific tumor markers, specifically CD69, CSF-1, and complement factor B (C1QBP)for PEL; IL1-beta, cyclinD3 and CD48for KS. We found that IL12, jun-B, msx-1 and thrombospondin 2 were associated with EBV co-infection in PEL. (ii) We defined the NFkB signature of Epstein-Barr virus (EBV)positive AIDS-associated Burkitt lymphoma(BL). This signature identified CCR5 as the key marker. (iii) This signature differed from EBV negative BL consistent with the idea that EBV not only activates NFkB activity but that this virus also reprograms NFkB signaling towards different targets. PMID:21792887

  15. Hepatitis C-associated liver carcinogenesis: Role of PML nuclear bodies

    PubMed Central

    Herzer, Kerstin; Gerken, Guido; Hofmann, Thomas G

    2014-01-01

    Successful escape from immune response characterises chronic hepatitis C virus (HCV) infection, which results in persistence of infection in about 80% of the patients. The deleterious consequences are cirrhosis and hepatocellular carcinoma. HCV accounts the most frequent cause for hepatocellular carcinoma (HCC) and liver transplantation (LT) in the western world. The underlying molecular mechanisms how HCV promotes tumor development are largely unknown. There is some in vitro and in vivo evidence that HCV interferes with the tumor suppressor PML and may thereby importantly contribute to the HCV-associated pathogenesis with respect to the development of HCC. The tumor suppressor protein “promyelocytic leukemia” (PML) has been implicated in the regulation of important cellular processes like differentiation and apoptosis. In cancer biology, PML and its associated nuclear bodies (NBs) have initially attracted intense interest due to its role in the pathogenesis of acute promyelocytic leukemia (APL). More recently, loss of PML has been implicated in human cancers of various histologic origins. Moreover, number and intensity of PML-NBs increase in response to interferons (IFNs) and there is evidence that PML-NBs may represent preferential targets in viral infections. Thus, PML could not only play a role in the mechanisms of the antiviral action of IFNs but may also be involved in a direct oncogenic effect of the HCV on hepatocytes. This review aims to summarise current knowledge about HCV-related liver carcinogenesis and to discuss a potential role of the nuclear body protein PML for this this hard-to-treat cancer. PMID:25253937

  16. A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology.

    PubMed

    2017-10-01

    This joint position paper illustrates the role and the correct use of echocardiography, radionuclide imaging with 18F-fluorodeoxyglucose positron emission tomography, radionuclide myocardial perfusion imaging and cardiovascular magnetic resonance imaging for the evaluation and management of patients with known or suspected cardiac sarcoidosis. This position paper will aid in standardizing imaging for cardiac sarcoidosis and may facilitate clinical trials and pooling of multi-centre data on cardiac sarcoidosis. Proposed flow charts for the work up and management of cardiac sarcoidosis are included. Copyright © 2017 European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology.

  17. Environmental problems associated with decommissioning the Chernobyl Nuclear Power Plant Cooling Pond.

    PubMed

    Oskolkov, B Ya; Bondarkov, M D; Gaschak, S P; Maksymenko, A M; Maksymenko, V M; Martynenko, V I; Farfán, E B; Jannik, G T; Marra, J C

    2010-11-01

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities associated with residual radioactive contamination of their territories is an imperative issue. Significant problems may result from decommissioning of cooling ponds with residual radioactive contamination. The Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond is one of the largest self-contained water reservoirs in the Chernobyl region and Ukrainian and Belorussian Polesye region. The 1986 ChNPP Reactor Unit Number Four significantly contaminated the ChNPP Cooling Pond. The total radionuclide inventory in the ChNPP Cooling Pond bottom deposits are as follows: ¹³⁷Cs: 16.28 ± 2.59 TBq; ⁹⁰Sr: 2.4 ± 0.48 TBq; and ²³⁹+²⁴⁰Pu: 0.00518 ± 0.00148 TBq. The ChNPP Cooling Pond is inhabited by over 500 algae species and subspecies, over 200 invertebrate species, and 36 fish species. The total mass of the living organisms in the ChNPP Cooling Pond is estimated to range from about 60,000 to 100,000 tons. The territory adjacent to the ChNPP Cooling Pond attracts many birds and mammals (178 bird species and 47 mammal species were recorded in the Chernobyl Exclusion Zone). This article describes several options for the ChNPP Cooling Pond decommissioning and environmental problems associated with its decommissioning. The article also provides assessments of the existing and potential exposure doses for the shoreline biota. For the 2008 conditions, the estimated total dose rate values were 11.4 40 μGy h⁻¹ for amphibians, 6.3 μGy h⁻¹ for birds, 15.1 μGy h⁻¹ for mammals, and 10.3 μGy h⁻¹ for reptiles, with the recommended maximum dose rate being equal to 40 μGy h⁻¹. However, drying the ChNPP Cooling Pond may increase the exposure doses to 94.5 μGy h⁻¹ for amphibians, 95.2 μGy h⁻¹ for birds, 284.0 μGy h⁻¹ for mammals, and 847.0 μGy h⁻¹ for reptiles. All of these anticipated dose rates exceed the recommended values.

  18. A new gene mapping resource: Interspecies hybrids between Pere David`s deer (Elaphurus davidianus) and red deer (Cervus elaphus)

    SciTech Connect

    Tate, M.L.; Mathias, H.C.; Penty, J.M.; Hill, D.F.; Fennessy, P.F.; Dodds, K.G.

    1995-03-01

    Three male F{sub 1} hybrids between Pere David`s deer and red deer were mated to red deer to produce 143 backcross calves. The pedigrees are a rare example of a fertile hybrid between evolutionarily divergent species. We examined the use of these families for genetic mapping of evolutionarily conserved (Type I) loci by testing for genetic linkage between five species-specific protein variants and 12 conserved DNA probes. Two probes were homologous, and the remainder syntenic, to the protein coding loci in cattle or humans. Using six restriction enzymes, each DNA probe detected one or more restriction fragments specific to Pere David`s deer. Linkage analyses among the species-specific variants placed the loci into four linkage groups within which linkage between adjacent loci and gene order was supported by a LOD > 3. Southern and protein analysis of LDHA and ALB provided identical segregation data. These linkage groups were consistent with the cattle gene map and provide new information for comparing the gene maps of ruminants, humans and mice. The deer hybrids are an important new resource that can contribute to the comparative analysis of the mammalian genome. 68 refs., 2 figs., 2 tabs.

  19. Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data.

    PubMed

    Dudbridge, Frank

    2008-01-01

    Missing data occur in genetic association studies for several reasons including missing family members and uncertain haplotype phase. Maximum likelihood is a commonly used approach to accommodate missing data, but it can be difficult to apply to family-based association studies, because of possible loss of robustness to confounding by population stratification. Here a novel likelihood for nuclear families is proposed, in which distinct sets of association parameters are used to model the parental genotypes and the offspring genotypes. This approach is robust to population structure when the data are complete, and has only minor loss of robustness when there are missing data. It also allows a novel conditioning step that gives valid analysis for multiple offspring in the presence of linkage. Unrelated subjects are included by regarding them as the children of two missing parents. Simulations and theory indicate similar operating characteristics to TRANSMIT, but with no bias with missing data in the presence of linkage. In comparison with FBAT and PCPH, the proposed model is slightly less robust to population structure but has greater power to detect strong effects. In comparison to APL and MITDT, the model is more robust to stratification and can accommodate sibships of any size. The methods are implemented for binary and continuous traits in software, UNPHASED, available from the author.

  20. Likelihood-Based Association Analysis for Nuclear Families and Unrelated Subjects with Missing Genotype Data

    PubMed Central

    Dudbridge, Frank

    2008-01-01

    Missing data occur in genetic association studies for several reasons including missing family members and uncertain haplotype phase. Maximum likelihood is a commonly used approach to accommodate missing data, but it can be difficult to apply to family-based association studies, because of possible loss of robustness to confounding by population stratification. Here a novel likelihood for nuclear families is proposed, in which distinct sets of association parameters are used to model the parental genotypes and the offspring genotypes. This approach is robust to population structure when the data are complete, and has only minor loss of robustness when there are missing data. It also allows a novel conditioning step that gives valid analysis for multiple offspring in the presence of linkage. Unrelated subjects are included by regarding them as the children of two missing parents. Simulations and theory indicate similar operating characteristics to TRANSMIT, but with no bias with missing data in the presence of linkage. In comparison with FBAT and PCPH, the proposed model is slightly less robust to population structure but has greater power to detect strong effects. In comparison to APL and MITDT, the model is more robust to stratification and can accommodate sibships of any size. The methods are implemented for binary and continuous traits in software, UNPHASED, available from the author. PMID:18382088

  1. Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

    PubMed

    Grant, Frederick D; Gelfand, Michael J; Drubach, Laura A; Treves, S Ted; Fahey, Frederic H

    2015-04-01

    Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients

  2. Nuclear networking.

    PubMed

    Xie, Wei; Burke, Brian

    2017-07-04

    Nuclear lamins are intermediate filament proteins that represent important structural components of metazoan nuclear envelopes (NEs). By combining proteomics and superresolution microscopy, we recently reported that both A- and B-type nuclear lamins form spatially distinct filament networks at the nuclear periphery of mouse fibroblasts. In particular, A-type lamins exhibit differential association with nuclear pore complexes (NPCs). Our studies reveal that the nuclear lamina network in mammalian somatic cells is less ordered and more complex than that of amphibian oocytes, the only other system in which the lamina has been visualized at high resolution. In addition, the NPC component Tpr likely links NPCs to the A-type lamin network, an association that appears to be regulated by C-terminal modification of various A-type lamin isoforms. Many questions remain, however, concerning the structure and assembly of lamin filaments, as well as with their mode of association with other nuclear components such as peripheral chromatin.

  3. Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer.

    PubMed

    Flote, Vidar G; Vettukattil, Riyas; Bathen, Tone F; Egeland, Thore; McTiernan, Anne; Frydenberg, Hanne; Husøy, Anders; Finstad, Sissi E; Lømo, Jon; Garred, Øystein; Schlichting, Ellen; Wist, Erik A; Thune, Inger

    2016-03-12

    High-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear. Among 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35-75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics. The breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m(2); total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5%. Most (93%) of the patients had estrogen receptor (ER) positive tumors (≥ 1% ER+), and 82% had progesterone receptor (PgR) positive tumors (≥ 10% PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22-0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51-1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28-4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36-1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1's contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No

  4. Fuel-Cycle and Nuclear Material Disposition Issues Associated with High-Temperature Gas Reactors

    SciTech Connect

    Shropshire, D.E.; Herring, J.S.

    2004-10-03

    The objective of this paper is to facilitate a better understanding of the fuel-cycle and nuclear material disposition issues associated with high-temperature gas reactors (HTGRs). This paper reviews the nuclear fuel cycles supporting early and present day gas reactors, and identifies challenges for the advanced fuel cycles and waste management systems supporting the next generation of HTGRs, including the Very High Temperature Reactor, which is under development in the Generation IV Program. The earliest gas-cooled reactors were the carbon dioxide (CO2)-cooled reactors. Historical experience is available from over 1,000 reactor-years of operation from 52 electricity-generating, CO2-cooled reactor plants that were placed in operation worldwide. Following the CO2 reactor development, seven HTGR plants were built and operated. The HTGR came about from the combination of helium coolant and graphite moderator. Helium was used instead of air or CO2 as the coolant. The helium gas has a significant technical base due to the experience gained in the United States from the 40-MWe Peach Bottom and 330-MWe Fort St. Vrain reactors designed by General Atomics. Germany also built and operated the 15-MWe Arbeitsgemeinschaft Versuchsreaktor (AVR) and the 300-MWe Thorium High-Temperature Reactor (THTR) power plants. The AVR, THTR, Peach Bottom and Fort St. Vrain all used fuel containing thorium in various forms (i.e., carbides, oxides, thorium particles) and mixtures with highly enriched uranium. The operational experience gained from these early gas reactors can be applied to the next generation of nuclear power systems. HTGR systems are being developed in South Africa, China, Japan, the United States, and Russia. Elements of the HTGR system evaluated included fuel demands on uranium ore mining and milling, conversion, enrichment services, and fuel fabrication; fuel management in-core; spent fuel characteristics affecting fuel recycling and refabrication, fuel handling, interim

  5. Novel Polymorphisms of Nuclear Receptor SHP Associated with Functional and Structural Changes

    PubMed Central

    Zhou, Taofeng; Zhang, Yuxia; Macchiarulo, Antonio; Yang, Zhihong; Cellanetti, Marco; Coto, Eliecer; Xu, Pingyi; Pellicciari, Roberto; Wang, Li

    2010-01-01

    We identified three heterozygous nonsynonymous single nucleotide polymorphisms in the small heterodimer partner (SHP, NROB2) gene in normal subjects and CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-like patients, including two novel missense mutations (p.R38H, p.K170N) and one of the previously reported polymorphism (p.G171A). Four novel heterozygous mutations were also identified in the intron (Intron1265T→A), 3′-untranslated region (3′-UTR101C→G, 3′-UTR186T→C), and promoter (Pro-423C→T) of the SHP gene. The exonic R38H and K170N mutants exhibited impaired nuclear translocation. K170N made SHP more susceptible to ubiquitination mediated degradation and blocked SHP acetylation, which displayed lost repressive activity on its interacting partners ERRγ and HNF4α but not LRH-1. In contrast, G171A increased SHP mRNA and protein expression and maintained normal function. In general, the interaction of SHP mutants with LRH-1 and EID1 was enhanced. K170N also markedly impaired the recruitment of SHP, HNF4α, HDAC1, and HDAC3 to the apoCIII promoter. Molecular dynamics simulations of SHP showed that G171A stabilized the nuclear receptor boxes, whereas K170N promoted the conformational destabilization of all the structural elements of the receptor. This study suggests that genetic variations in SHP are common among human subjects and the Lys-170 residue plays a key role in controlling SHP ubiquitination and acetylation associated with SHP protein stability and repressive function. PMID:20516075

  6. An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release

    SciTech Connect

    Adamik, Barbara; Islam, Aminul; Rouhani, Farshid N.; Hawari, Feras I.; Zhang Jing; Levine, Stewart J.

    2008-07-04

    The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released to the extracellular space by two mechanisms, the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Both pathways appear to be regulated by an interaction between TNFR1 and ARTS-1 (aminopeptidase regulator of TNFR1 shedding). Here, we sought to identify ARTS-1-interacting proteins that modulate TNFR1 release. Co-immunoprecipitation identified an association between ARTS-1 and RBMX (RNA-binding motif gene, X chromosome), a 43-kDa heterogeneous nuclear ribonucleoprotein. RNA interference attenuated RBMX expression, which reduced both the constitutive release of TNFR1 exosome-like vesicles and the IL-1{beta}-mediated inducible proteolytic cleavage of soluble TNFR1 ectodomains. Reciprocally, over-expression of RBMX increased TNFR1 exosome-like vesicle release and the IL-1{beta}-mediated inducible shedding of TNFR1 ectodomains. This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains.

  7. Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes

    SciTech Connect

    Rahayu, Retno; Ohsaki, Eriko; Omori, Hiroko; Ueda, Keiji

    2016-09-15

    In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super-resolution laser confocal microscopy and correlative fluorescence microscopy–electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. - Highlights: • This is the first report showing LANA dots on mitotic chromosomes by fluorescent microscopy followed by electron microscopy. • LANA dots localized randomly on condensed chromosomes other than centromere/pericentromere and telomere/peritelomre. • Cellular mitotic checkpoint should not be always involved in the segregation of KSHV genomes in the latency.

  8. Senescent cells develop a PARP-1 and nuclear factor-κB-associated secretome (PNAS)

    PubMed Central

    Ohanna, Mickaël; Giuliano, Sandy; Bonet, Caroline; Imbert, Véronique; Hofman, Véronique; Zangari, Joséphine; Bille, Karine; Robert, Caroline; Bressac-de Paillerets, Brigitte; Hofman, Paul; Rocchi, Stéphane; Peyron, Jean-François; Lacour, Jean-Philippe; Ballotti, Robert; Bertolotto, Corine

    2011-01-01

    Melanoma cells can enter the process of senescence, but whether they express a secretory phenotype, as reported for other cells, is undetermined. This is of paramount importance, because this secretome can alter the tumor microenvironment and the response to chemotherapeutic drugs. More generally, the molecular events involved in formation of the senescent-associated secretome have yet to be determined. We reveal here that melanoma cells experiencing senescence in response to diverse stimuli, including anti-melanoma drugs, produce an inflammatory secretory profile, where the chemokine ligand-2 (CCL2) acts as a critical effector. Thus, we reveal how senescence induction might be involved in therapeutic failure in melanoma. We further provide a molecular relationship between senescence induction and secretome formation by revealing that the poly(ADP-ribose) polymerase-1 (PARP-1)/nuclear factor-κB (NF-κB) signaling cascade, activated during senescence, drives the formation of a secretome endowed with protumoral and prometastatic properties. Our findings also point to the existence of the PARP-1 and NF-κB-associated secretome, termed the PNAS, in nonmelanoma cells. Most importantly, inhibition of PARP-1 or NF-κB prevents the proinvasive properties of the secretome. Collectively, identification of the PARP-1/NF-κB axis in secretome formation opens new avenues for therapeutic intervention against cancers. PMID:21646373

  9. Intraspecific host selection of Père David's deer by cattle egrets in Dafeng, China.

    PubMed

    Fernandez, Eve V; Li, Zhongqiu; Zheng, Wei; Ding, Yuhua; Sun, Daming; Che, Ye

    2014-06-01

    Studies have focused on foraging ecology of cattle egrets (Bubulcus ibis) and their selection of ungulate host species. However, few studies have been conducted at intraspecific levels, such as the sex/age class of a specific ungulate. In this study, the foraging behavior and intraspecific host selection of cattle egrets associated with Père David's deer (Elaphurus davidianus) were investigated at the Dafeng National Nature Reserve, China in summer 2011 and 2012. Egret-deer pairing status was analyzed and intraspecific host selection index was calculated. Cattle egrets preferred to feed with female deer compared with male deer and fawns. In contrast to solitary birds, cattle egrets following a deer benefited from a relatively low vigilance output, high foraging success, low energy expenditure, and high total foraging yields. These egrets also maximized benefits when they followed female deer compared with male deer and fawns. Our results further indicated that egrets likely preferred females because of the appropriate moving speed that allowed these egrets to follow and forage sufficiently and effectively. The males of Père David's deer were possibly more aggressive than the females during the rutting season, causing egrets to experience difficulty in accompaniment and feeding. Fawns were not preferred because they were usually motionless and insufficiently large to stir more insects. We did not find any behavioral differences in vigilance and feeding between juveniles and adults. Our results suggested that cattle egrets could obtain significant benefits from their association with Père David's deer, and these benefits were maximized when they followed female deer. This article is part of a Special Issue entitled: insert SI title.

  10. Radar detection of pedestrian-induced vibrations on Michelangelo's David.

    PubMed

    Pieraccini, Massimiliano; Betti, Michele; Forcellini, Davide; Dei, Devis; Papi, Federico; Bartoli, Gianni; Facchini, Luca; Corazzi, Riccardo; Kovacevic, Vladimir Cerisano

    2017-01-01

    This paper summarizes the results of a two-day dynamic monitoring of Michelangelo's David subject to environmental loads (city traffic and pedestrian loading induced by tourists visiting the Accademia Gallery). The monitoring was carried out by a no-contact technique using an interferometric radar, whose effectiveness in measuring the resonant frequencies of structures and historic monuments has proved over the last years through numerous monitoring activities. Owing to the dynamic behavior of the measurement system (radar and tripod), an accelerometer has been installed on the radar head to filter out the movement component of the measuring instrument from the measurement of the David's displacement. Measurements were carried out in the presence and absence of visitors, to assess their influence on the dynamic behavior of the statue. A numerical model of the statue was employed to evaluate the experimental results.

  11. David Nelson, MD, MPH | Division of Cancer Prevention

    Cancer.gov

    Dr. David E Nelson is the Director of the Cancer Prevention Fellowship Program (CPFP) Branch in the National Cancer Institute's Division of Cancer Prevention. The CPFP is an internationally renowned postdoctoral program designed to train early career scientific researchers and leaders in the field of cancer prevention. Dr. Nelson came to the CPFP in 2008 after working at the Centers for Disease Control and Prevention in Atlanta for many years. |

  12. APOLLO XII CREW - WELCOME - USS HORNET - REAR ADMIRAL DONALD DAVID

    NASA Image and Video Library

    1969-11-24

    S69-22876 (24 Nov. 1969) --- Rear Admiral Donald C. David, Commander, Manned Spacecraft Recovery Force, Pacific, welcomes the crew of the Apollo 12 lunar landing mission aboard the USS Hornet, prime recovery vessel for the mission. A color guard was also on hand for the welcoming ceremonies. Inside the Mobile Quarantine Facility (MQF) are (left to right) astronauts Charles Conrad Jr., commander; Richard F. Gordon Jr., command module pilot; and Alan L. Bean, lunar module pilot.

  13. STS-86 Mission Specialist David Wolf in white room

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-86 Mission Specialist David A. Wolf, at center facing camera, prepares to enter the Space Shuttle Atlantis at Launch Pad 39A, with the assistance of Rick Welty, in foreground at center, United Space Alliance (USA) orbiter vehicle closeout chief; and closeout team members, in background from left, Jim Davis, NASA quality assurance specialist; and George Schramm, USA mechanical technician. STS-86 Mission Specialist Vladimir Georgievich Titov, in foreground at far left, is awaiting his turn.

  14. STS-107 Mission Specialist David Brown suits up for TCDT

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- STS-107 Mission Specialist David Brown happily submits to suit check prior to Terminal Countdown Demonstration Test activities, which include a simulated launch countdown at the pad. STS-107 is a mission devoted to research and will include more than 80 experiments that will study Earth and space science, advanced technology development, and astronaut health and safety. Launch is planned for Jan. 16, 2003, between 10 a.m. and 2 p.m. EST aboard Space Shuttle Columbia. .

  15. Astronaut David Wolf in medical experiment in SLS-2

    NASA Image and Video Library

    1993-10-28

    STS058-204-014 (18 Oct.-1 Nov. 1993) --- Astronaut David A. Wolf, mission specialist, participates in an experiment that investigates in-space distribution and movement of blood and gas in the pulmonary system. The data gathered during the two-week flight will be compared with results of tests performed on Earth to determine the changes that occur in pulmonary functions. Photo credit: NASA

  16. Digital Anthropometric Video-Imaging Device (DAVID) Operational Manual

    DTIC Science & Technology

    2002-08-29

    wish to thank John Joseph ofIsoperformance, Inc., for developing the initial Visual Basic program for the DAVID and the staff of SPA WAR System Center...operator in demographic data field of Remote Program 3. DIMENSIONNAME: Name of dimension in Microsoft Visual Basic program 4. SHORTNAME: Abbreviation for...measurement (e.g., SH, HT, etc.) in Microsoft Visual Basic program 5. ISCALIB: Switch in Microsoft Visual Basic program to indicate if measurement is

  17. About David Ruelle, After His 80th Birthday

    NASA Astrophysics Data System (ADS)

    Gallavotti, Giovanni

    2017-02-01

    This is, with minor modifications, a text read at the 114th Statistical Mechanics meeting, in honor of D. Ruelle and Y. Sinai, at Rutgers, Dec. 13-15, 2015. It does not attempt to analyze, or not even just quote, all works of David Ruelle; I discuss, as usual in such occasions, a few among his works with which I have most familiarity and which were a source of inspiration for me.

  18. Reporting nuclear cardiology: a joint position paper by the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI).

    PubMed

    Trägårdh, Elin; Hesse, Birger; Knuuti, Juhani; Flotats, Albert; Kaufmann, Philipp A; Kitsiou, Anastasia; Hacker, Marcus; Verberne, Hein J; Edenbrandt, Lars; Delgado, Victoria; Donal, Erwan; Edvardsen, Thor; Galderisi, Maurizio; Habib, Gilbert; Lancellotti, Patrizio; Nieman, Koen; Rosenhek, Raphael; Agostini, Denis; Gimelli, Alessia; Lindner, Oliver; Slart, Riemert; Ubleis, Christopher

    2015-03-01

    The report of an imaging procedure is a critical component of an examination, being the final and often the only communication from the interpreting physician to the referring or treating physician. Very limited evidence and few recommendations or guidelines on reporting imaging studies are available; therefore, an European position statement on how to report nuclear cardiology might be useful. The current paper combines the limited existing evidence with expert consensus, previously published recommendations as well as current clinical practices. For all the applications discussed in this paper (myocardial perfusion, viability, innervation, and function as acquired by single photon emission computed tomography and positron emission tomography or hybrid imaging), headings cover laboratory and patient demographics, clinical indication, tracer administration and image acquisition, findings, and conclusion of the report. The statement also discusses recommended terminology in nuclear cardiology, image display, and preliminary reports. It is hoped that this statement may lead to more attention to create well-written and standardized nuclear cardiology reports and eventually lead to improved clinical outcome.

  19. Nuclear translocation of the cytoskeleton-associated protein, smALP, upon induction of skeletal muscle differentiation

    SciTech Connect

    Cambier, Linda; Pomies, Pascal

    2011-06-17

    Highlights: {yields} The cytoskeleton-associated protein, smALP, is expressed in differentiated skeletal muscle. {yields} smALP is translocated from the cytoplasm to the nucleus of C2C12 myoblasts upon induction of myogenesis. {yields} The differentiation-dependent nuclear translocation of smALP occurs in parallel with the nuclear accumulation of myogenin. {yields} The LIM domain of smALP is essential for the nuclear accumulation of the protein. {yields} smALP might act in the nucleus to control some critical aspect of the muscle differentiation process. -- Abstract: The skALP isoform has been shown to play a critical role in actin organization and anchorage within the Z-discs of skeletal muscles, but no data is available on the function of the smALP isoform in skeletal muscle cells. Here, we show that upon induction of differentiation a nuclear translocation of smALP from the cytoplasm to the nucleus of C2C12 myoblasts, concomitant to an up-regulation of the protein expression, occurs in parallel with the nuclear accumulation of myogenin. Moreover, we demonstrate that the LIM domain of smALP is essential for the nuclear translocation of the protein.

  20. Proliferation dangers associated with nuclear medicine: getting weapons-grade uranium out of radiopharmaceutical production.

    PubMed

    Williams, Bill; Ruff, Tilman A

    2007-01-01

    Abolishing the threat of nuclear war requires the outlawing of nuclear weapons and dismantling current nuclear weapon stockpiles, but also depends on eliminating access to fissile material (nuclear weapon fuel). The near-universal use of weapons-grade, highly enriched uranium (HEU) to produce radiopharmaceuticals is a significant proliferation hazard. Health professionals have a strategic opportunity and obligation to progress the elimination of medically-related commerce in HEU, closing one of the most vulnerable pathways to the much-feared 'terrorist bomb'.

  1. Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation.

    PubMed

    Chen, Wei-Yen; Lin, Chia-Lung; Chuang, Jen-Hua; Chiu, Fu-Yu; Sun, Yun-Ya; Liang, Mei-Chih; Lin, Yenshou

    2017-01-20

    Mammalian target of rapamycin (mTOR) plays a range of crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, mTOR complex 1 and mTOR complex 2 (mTORC1 and mTORC2), via association with a series of different components; this allows the complexes to execute their wide range of functions. This study explores further the composition of the mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation and mass spectrometry, a novel Rictor associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified. The association between hnRNP M and Rictor was verified using recombinant and endogenous protein and the binding site was found to be within aa 1~532 of hnRNP M. The presence of hnRNP M significantly affects phosphorylation of SGK1 S422, but not of Akt S473, PKCα S657 and PKCζ T560. Furthermore, hnRNP M also plays a critical role in muscle differentiation because knock-down of either hnRNP M or Rictor in C2C12 myoblasts reduced differentiation. This decrease is able to be rescued by overexpression SGK S422D in hnRNP M knockdown C2C12 myoblasts. Taken together, we have identified a novel Rictor/mTOR binding molecule, hnRNP M, that allows mTORC2 signaling to phosphorylate SGK1 thus regulating muscle differentiation.

  2. Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation

    PubMed Central

    Chen, Wei-Yen; Lin, Chia-Lung; Chuang, Jen-Hua; Chiu, Fu-Yu; Sun, Yun-Ya; Liang, Mei-Chih; Lin, Yenshou

    2017-01-01

    Mammalian target of rapamycin (mTOR) plays a range of crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, mTOR complex 1 and mTOR complex 2 (mTORC1 and mTORC2), via association with a series of different components; this allows the complexes to execute their wide range of functions. This study explores further the composition of the mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation and mass spectrometry, a novel Rictor associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified. The association between hnRNP M and Rictor was verified using recombinant and endogenous protein and the binding site was found to be within aa 1~532 of hnRNP M. The presence of hnRNP M significantly affects phosphorylation of SGK1 S422, but not of Akt S473, PKCα S657 and PKCζ T560. Furthermore, hnRNP M also plays a critical role in muscle differentiation because knock-down of either hnRNP M or Rictor in C2C12 myoblasts reduced differentiation. This decrease is able to be rescued by overexpression SGK S422D in hnRNP M knockdown C2C12 myoblasts. Taken together, we have identified a novel Rictor/mTOR binding molecule, hnRNP M, that allows mTORC2 signaling to phosphorylate SGK1 thus regulating muscle differentiation. PMID:28106162

  3. The Nuclear Receptor, Nor-1, Induces the Physiological Responses Associated With Exercise

    PubMed Central

    Goode, Joel M.; Tuong, Zewen K.; Wang, Shu-Ching M.; Oh, Tae Gyu; Shao, Emily X.

    2016-01-01

    Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling response to physical activity can ameliorate/prevent diseases associated with poor diet and lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives muscle reprogramming, improves exercise endurance, and oxidative metabolism. The current manuscript investigates the association between exercise, Nor-1 expression and the role of Nor-1 in adaptive remodeling. We demonstrate that Nor-1 expression is induced by exercise and is dependent on calcium/calcineurin signaling (in vitro and in vivo). Analysis of fatigue-resistant transgenic mice that express Nor-1 in skeletal muscle revealed increased hypertrophy and vascularization of muscle tissue. Moreover, we demonstrate that transgenic Nor-1 expression is associated with increased intracellular recycling, ie, autophagy, involving 1) increased expression of light chain 3A or LC3A-II, autophagy protein 5, and autophagy protein 12 in quadriceps femoris muscle extracts from Tg-Nor-1 (relative to Wild-type (WT) littermates); 2) decreased p62 expression indicative of increased autophagolysosome assembly; and 3) decreased mammalian target of rapamycin complex 1 activity. Transfection of LC3A-GFP-RFP chimeric plasmid demonstrated that autophagolysosome formation was significantly increased by Nor-1 expression. Furthermore, we demonstrated a single bout of exercise induced LC3A-II expression in skeletal muscle from C57BL/6 WT mice. This study, when combined with our previous studies, demonstrates that Nor-1 expression drives multiple physiological changes/pathways that are critical to the beneficial responses of muscle to exercise and provides insights into potential pharmacological manipulation of muscle reprogramming for the treatment of lifestyle induced chronic diseases. PMID:27144290

  4. 76 FR 42159 - Lifting of Sanctions on Person Associated With the A.Q. Khan Nuclear Procurement Network

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-18

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF STATE Lifting of Sanctions on Person Associated With the A.Q. Khan Nuclear Procurement Network AGENCY: Bureau of International Security and Nonproliferation, Department of State. ACTION: Notice. SUMMARY: A determination has...

  5. Tissue-specific expression and cDNA cloning of small nuclear ribonucleoprotein-associated polypeptide N

    SciTech Connect

    McAllister, G.; Amara, S.G.; Lerner, M.R. )

    1988-07-01

    Sera from some patients with systemic lupus erythematosus and other autoimmune diseases have antibodies against nuclear antigens. An example is anti-Sm sera, which recognize proteins associated with small nuclear RNA molecules (small nuclear ribonucleoprotein (snRNP) particles). In this paper anti-Sm sera were used to probe immunoblots of various rat tissues. A previously unidentified M{sub r} 28,000 polypeptide was recognized by these anti-Sm sera. This polypeptide, referred to as N, is expressed in a tissue-specific manner, being most abundant in rat brain, less so in heart, and undetectable in the other tissues examined. Immunoprecipitation experiments using antibodies directed against the cap structure of small nuclear RNAs have demonstrated that N is a snRNP-associated polypeptide. Anti-Sm serum was also used to isolate a partial cDNA clone ({lambda}rb91) from a rat brain phage {lambda}gt11 cDNA expression library. A longer cDNA clone was obtained by rescreening the library with {lambda}rb91. In vitro transcription and subsequent translation of this subcloned, longer insert (pGMA2) resulted in a protein product with the same electrophoretic and immunological properties as N, confirming that pGMA2 encodes N. The tissue distribution of N and the involvement of snRNP particles in nuclear pre-mRNA processing may imply a role for N in tissue-specific pre-mRNA splicing.

  6. Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells

    SciTech Connect

    Sanna, Elena; Miotti, Silvia . E-mail: silvia.miotti@istitutotumori.mi.it; Mazzi, Mimma; De Santis, Giuseppina; Canevari, Silvana; Tomassetti, Antonella

    2007-04-15

    Caveolin-1 (cav-1), a member of a protein family associated mainly with cell membrane microdomains in many cell types, acts as a tumor suppressor in ovarian carcinoma cells. Biochemical analyses demonstrated that cav-1 was also localized in the nuclei of ovarian carcinoma cells, endogenously (SKOV3) or ectopically (IGtC3) expressing cav-1. By confocal analyses, the same cell lines as well as IGROV1 and SKOV3 cells transiently transfected with green fluorescent protein-cav-1 fusion protein showed nuclear punctate speckled pattern. Subnuclear distribution analysis revealed cav-1 mainly associated with the nuclear matrix, but also slightly with chromatin. Cav-1 was found in nuclear high-molecular weight complexes and by confocal analysis was found to co-localized with the inner nuclear membrane protein emerin. Cyclin D1 and folate receptor promoters were modulated by cav-1 in SKOV3 cells as demonstrated by transient transfection with or silencing of cav-1. Chromatin immunoprecipitation and supershift assays indicated that nuclear cav-1 can bind in vitro and in vivo to promoter sequences of both cyclin D1 and folate receptor genes. These data suggest that in ovarian carcinoma cells cav-1, localized in transcriptionally inactive chromatin, exerts a functional activity mediated, at least in part, by directly binding to sequences of genes involved in proliferation.

  7. Abnormal mitosis in hypertetraploid cells causes aberrant nuclear morphology in association with H2O2-induced premature senescence.

    PubMed

    Ohshima, Susumu

    2008-09-01

    Aberrant nuclear morphology, such as nuclei with irregular shapes or fragmented nuclei, is often observed in senescent cells, but its biological significance is not fully understood. My previous study showed that aberrant nuclear morphology in senescent human fibroblasts is attributable to abnormal mitosis in later passages. In this study, the production of abnormal nuclei in association with premature senescence was investigated. Premature senescence was induced by brief exposure of human fibroblasts to hydrogen peroxide (H(2)O(2)), and mitosis was observed by time-lapse microscopy. In addition, cell cycle and nuclear morphology after exposure to H(2)O(2) were also analyzed using a laser scanning cytometer. Time-lapse analysis revealed that the induction of premature senescence caused abnormal mitoses, such as mitotic slippage or incomplete mitosis, especially in later days after H(2)O(2) exposure and often resulted in abnormal nuclear morphology. Analysis by laser scanning cytometer showed significantly higher frequency of abnormal cells with deformed nuclei and abnormal mitotic cells with misaligned chromosomes in a hypertetraploid subpopulation. These results suggest that unstable hypertetraploid cells, formed in association with H(2)O(2)-induced premature senescence, cause abnormal mitosis that leads to aberrant nuclear morphology.

  8. Cytoplasmic intermediate filaments are stably associated with nuclear matrices and potentially modulate their DNA-binding function.

    PubMed

    Tolstonog, Genrich V; Sabasch, Michael; Traub, Peter

    2002-03-01

    The tight association of cytoplasmic intermediate filaments (cIFs) with the nucleus and the isolation of crosslinkage products of vimentin with genomic DNA fragments, including nuclear matrix attachment regions (MARs) from proliferating fibroblasts, point to a participation of cIFs in nuclear activities. To test the possibility that cIFs are complementary nuclear matrix elements, the nuclei of a series of cultured cells were subjected to the Li-diiodosalicylate (LIS) extraction protocol developed for the preparation of nuclear matrices and analyzed by immunofluorescence microscopy and immunoblotting with antibodies directed against lamin B and cIF proteins. When nuclei released from hypotonically swollen L929 suspension cells in the presence of digitonin or Triton X-100 were exposed to such strong shearing forces that a considerable number were totally disrupted, a thin, discontinuous layer of vimentin IFs remained tenaciously adhering to still intact nuclei, in apparent coalignment with the nuclear lamina. Even in broken nuclei, the distribution of vimentin followed that of lamin B in areas where the lamina still appeared intact. The same retention of vimentin together with desmin and glial IFs was observed on the nuclei isolated from differentiating C2C12 myoblast and U333 glioma cells, respectively. Nuclei from epithelial cells shed their residual perinuclear IF layers as coherent cytoskeletal ghosts, except for small fractions of vimentin and cytokeratin IFs, which remained in a dot-to cap-like arrangement on the nuclear surface, in apparent codistribution with lamin B. LIS extraction did not bring about a reduction in the cIF protein contents of such nuclei upon their transformation into nuclear matrices. Moreover, in whole mount preparations of mouse embryo fibroblasts, DNA/chromatin emerging from nuclei during LIS extraction mechanically and chemically cleaned the nuclear surface and perinuclear area from loosely anchored cytoplasmic material with the

  9. Prostate Cancer Expression Profiles of Cytoplasmic ERβ1 and Nuclear ERβ2 are Associated with Poor Outcomes following Radical Prostatectomy.

    PubMed

    Schade, George R; Holt, Sarah K; Zhang, Xiaotun; Song, Dan; Wright, Jonathan L; Zhao, Shanshan; Kolb, Suzanne; Lam, Hung-Ming; Levin, Linda; Leung, Yuet-Kin; Ho, Shuk-Mei; Stanford, Janet L

    2016-06-01

    Existing data regarding the expression of estrogen receptors (ERs) and prostate cancer outcomes have been limited. We evaluated the relationship of expression profiles of ERβ subtypes and the ER GPR30 (G-protein-coupled receptor-30) with patient factors at diagnosis and outcomes following radical prostatectomy. Tissue microarrays constructed using samples from 566 men with long-term clinical followup were analyzed by immunohistochemistry targeting ERβ1, ERβ2, ERβ5 and GPR30. An experienced pathologist scored receptor distribution and staining intensity. Tumor staining characteristics were evaluated for associations with patient characteristics, recurrence-free survival and prostate cancer specific mortality following radical prostatectomy. Prostate cancer cells had unique receptor subtype staining patterns. ERβ1 demonstrated predominantly nuclear localization while ERβ2, ERβ5 and GPR30 were predominantly cytoplasmic. After controlling for patient factors intense cytoplasmic ERβ1 staining was independently associated with time to recurrence (HR 1.7, 95% CI 1.1-2.6, p = 0.01) and prostate cancer specific mortality (HR 6.6, 95% CI 1.8-24.9, p = 0.01). Intense nuclear ERβ2 staining was similarly independently associated with prostate cancer specific mortality (HR 3.9, 95% CI 1.1-13.4, p = 0.03). Patients with cytoplasmic ERβ1 and nuclear ERβ2 co-staining had significantly worse 15-year prostate cancer specific mortality than patients with expression of only cytoplasmic ERβ1, only nuclear ERβ2 and neither ER (16.4%, 4.3%, 0.0% and 2.0 %, respectively, p = 0.001). Increased cytoplasmic ERβ1 and nuclear ERβ2 expression is associated with worse cancer specific outcomes following radical prostatectomy. These findings suggest that tumor ERβ1 and ERβ2 staining patterns provide prognostic information on patients treated with radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All

  10. Cardiovascular disease associated with radiotherapy: activation of nuclear factor kappa-B.

    PubMed

    Halle, M; Hall, P; Tornvall, P

    2011-05-01

    There have been several recent reports of an increased risk of cardiovascular disease after radiotherapy. Hence, with an increasing number of cancer survivors, the incidence of cardiovascular disease caused by radiotherapy will increase. The existence of a type of vascular disease, or vasculopathy, induced by radiotherapy has been known for decades. It is important to identify and understand the molecular causes of this vasculopathy to determine preventive strategies. Recently, a chronic inflammation with similarities to atherosclerosis has been observed, with activation of the transcription factor nuclear factor kappa-B (NF-κB) as a possible cause. However, the trigger for NF-κB activation is unclear although it may be that reactive oxygen species or direct DNA damage is involved. To minimize the risk of cardiovascular disease in vulnerable patients, careful selection of patients, radiation dose and fractionation are important, together with the development of new techniques that reduce radiation dose to the blood vessels. In the light of the finding of an interaction between risk factors for cardiovascular disease and radiotherapy, it is reasonable to modify these factors including diabetes mellitus, hyperlipidaemia, hypertension and smoking. We believe that preventive strategies focusing on NF-κB can reduce the risk of future adverse cardiovascular events. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  11. Systematic and Statistical Errors Associated with Nuclear Decay Constant Measurements Using the Counting Technique

    NASA Astrophysics Data System (ADS)

    Koltick, David; Wang, Haoyu; Liu, Shih-Chieh; Heim, Jordan; Nistor, Jonathan

    2016-03-01

    Typical nuclear decay constants are measured at the accuracy level of 10-2. There are numerous reasons: tests of unconventional theories, dating of materials, and long term inventory evolution which require decay constants accuracy at a level of 10-4 to 10-5. The statistical and systematic errors associated with precision measurements of decays using the counting technique are presented. Precision requires high count rates, which introduces time dependent dead time and pile-up corrections. An approach to overcome these issues is presented by continuous recording of the detector current. Other systematic corrections include, the time dependent dead time due to background radiation, control of target motion and radiation flight path variation due to environmental conditions, and the time dependent effects caused by scattered events are presented. The incorporation of blind experimental techniques can help make measurement independent of past results. A spectrometer design and data analysis is reviewed that can accomplish these goals. The author would like to thank TechSource, Inc. and Advanced Physics Technologies, LLC. for their support in this work.

  12. Association between Long Interspersed Nuclear Element-1 Methylation and Relative Telomere Length in Wilms Tumor

    PubMed Central

    Chang, Hui-Bo; Zou, Ji-Zhen; He, Cai; Zeng, Rui; Li, Yuan-Yuan; Ma, Fei-Fei; Liu, Zhuo; Ye, Hui; Wu, Jian-Xin

    2015-01-01

    Background: DNA hypomethylation of long interspersed nuclear elements-1 (LINEs-1) occurs during carcinogenesis, whereas information addressing LINE-1 methylation in Wilms tumor (WT) is limited. The main purpose of our study was to quantify LINE-1 methylation levels and evaluate their relationship with relative telomere length (TL) in WT. Methods: We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction (PCR) pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. Results: LINE-1 methylation levels were significantly lower (P < 0.05) and relative TLs were significantly shorter (P < 0.05) in WT compared with normal kidney. There was a significant positive relationship between LINE-1 methylation and relative TL in WT (r = 0.671, P = 0.001). LINE-1 Methylation levels were significantly associated with global DNA methylation (r = 0.332, P < 0.01). In addition, relative TL was shortened and LINE-1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2′-deoxycytidine compared with untreated WT cell line. Conclusion: These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT. PMID:26608986

  13. Breast Cancer–Associated Abraxas Mutation Disrupts Nuclear Localization and DNA Damage Response Functions

    PubMed Central

    Solyom, Szilvia; Aressy, Bernadette; Pylkäs, Katri; Patterson-Fortin, Jeffrey; Hartikainen, Jaana M.; Kallioniemi, Anne; Kauppila, Saila; Nikkilä, Jenni; Kosma, Veli-Matti; Mannermaa, Arto; Greenberg, Roger A.; Winqvist, Robert

    2013-01-01

    Breast cancer is the most common cancer in women in developed countries and has a well-established genetic component. Germline mutations in a network of genes encoding BRCA1, BRCA2, and their interacting partners confer hereditary susceptibility to breast cancer. Abraxas directly interacts with the BRCA1 BRCT (BRCA1 carboxyl-terminal) repeats and contributes to BRCA1-dependent DNA damage responses, making Abraxas a candidate for yet unexplained disease susceptibility. Here, we have screened 125 Northern Finnish breast cancer families for coding region and splice-site Abraxas mutations and genotyped three tagging single-nucleotide polymorphisms within the gene from 991 unselected breast cancer cases and 868 female controls for common cancer-associated variants. A novel heterozygous alteration, c.1082G>A (Arg361Gln), that results in abrogated nuclear localization and DNA response activities was identified in three breast cancer families and in one additional familial case from an unselected breast cancer cohort, but not in healthy controls (P = 0.002). On the basis of its exclusive occurrence in familial cancers, disease cosegregation, evolutionary conservation, and disruption of critical BRCA1 functions, the recurrent Abraxas c.1082G>A mutation connects to cancer predisposition. These findings contribute to the concept of a BRCA-centered tumor suppressor network and provide the identity of Abraxas as a new breast cancer susceptibility gene. PMID:22357538

  14. Identification and Evaluation of Human Factors Issues Associated with Emerging Nuclear Plant Technology

    SciTech Connect

    O'Hara,J.M.; Higgins,J.; Brown, William S.

    2009-04-01

    This study has identified human performance research issues associated with the implementation of new technology in nuclear power plants (NPPs). To identify the research issues, current industry developments and trends were evaluated in the areas of reactor technology, instrumentation and control technology, human-system integration technology, and human factors engineering (HFE) methods and tools. The issues were prioritized into four categories based on evaluations provided by 14 independent subject matter experts representing vendors, utilities, research organizations and regulators. Twenty issues were categorized into the top priority category. The study also identifies the priority of each issue and the rationale for those in the top priority category. The top priority issues were then organized into research program areas of: New Concepts of Operation using Multi-agent Teams, Human-system Interface Design, Complexity Issues in Advanced Systems, Operating Experience of New and Modernized Plants, and HFE Methods and Tools. The results can serve as input to the development of a long-term strategy and plan for addressing human performance in these areas to support the safe operation of new NPPs.

  15. Association between Long Interspersed Nuclear Element-1 Methylation and Relative Telomere Length in Wilms Tumor.

    PubMed

    Chang, Hui-Bo; Zou, Ji-Zhen; He, Cai; Zeng, Rui; Li, Yuan-Yuan; Ma, Fei-Fei; Liu, Zhuo; Ye, Hui; Wu, Jian-Xin

    2015-11-20

    DNA hypomethylation of long interspersed nuclear elements-1 (LINEs-1) occurs during carcinogenesis, whereas information addressing LINE-1 methylation in Wilms tumor (WT) is limited. The main purpose of our study was to quantify LINE-1 methylation levels and evaluate their relationship with relative telomere length (TL) in WT. We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction (PCR) pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. LINE-1 methylation levels were significantly lower (P < 0.05) and relative TLs were significantly shorter (P < 0.05) in WT compared with normal kidney. There was a significant positive relationship between LINE-1 methylation and relative TL in WT (r = 0.671, P = 0.001). LINE-1 Methylation levels were significantly associated with global DNA methylation (r = 0.332, P < 0.01). In addition, relative TL was shortened and LINE-1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2'-deoxycytidine compared with untreated WT cell line. These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.

  16. Small nuclear ribonucleoprotein associated polypeptide N accelerates cell proliferation in pancreatic adenocarcinoma.

    PubMed

    Ma, Jin; Zhang, Zhuo; Wang, Jiancheng

    2015-10-01

    The spliceosome, the large RNA‑protein molecular complex, is crucial for pre‑mRNA splicing. Several antitumor drugs have been found to tightly bind to the components of the spliceosome and mutations in the spliceosome have been reported in several types of cancer. However, the involvement of the spliceosome in pancreatic adenocarcinoma remains unclear. In the present study, small nuclear ribonucleoprotein associated polypeptide N (SNRPN), a key constituent of spliceosomes, was disrupted in BxPC‑3 pancreatic adenocarcinoma cells using lentivirus‑mediated RNA interference (RNAi). It was found that knockdown of SNRPN reduced the proliferation ability of BxPC‑3 cells, as determined by an MTT assay. Furthermore, cell colony formation was impaired in SNRPN depleted adenocarcinoma cells and cell cycle analysis showed that depletion of SNRPN led to S phase cell cycle arrest and apoptosis. These results suggest that SNRPN is a key player in pancreatic adenocarcinoma cell growth, and targeted loss of SNRPN may be a potential therapeutic method for pancreatic cancer.

  17. Nuclear weapons, nuclear effects, nuclear war

    SciTech Connect

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  18. Associated-particle sealed-tube neutron probe: Detection of explosives, contraband, and nuclear materials

    SciTech Connect

    Rhodes, E.; Dickerman, C.E.

    1996-05-01

    Continued research and development of the APSTNG shows the potential for practical field use of this technology for detection of explosives, contraband, and nuclear materials. The APSTNG (associated-particle sealed-tube generator) inspects the item to be examined using penetrating 14-MeV neutrons generated by the deuterium-tritium reaction inside a compact accelerator tube. An alpha detector built into the sealed tube detects the alpha-particle associated with each neutron emitted in a cone encompassing the volume to be inspected. Penetrating high-energy gamma-rays from the resulting neutron reactions identify specific nuclides inside the volume. Flight-times determined from the detection times of gamma-rays and alpha-particles separate the prompt and delayed gamma-ray spectra and allow a coarse 3-D image to be obtained of nuclides identified in the prompt spectrum. The generator and detectors can be on the same side of the inspected object, on opposite sides, or with intermediate orientations. Thus, spaces behind walls and other confined regions can be inspected. Signals from container walls can be discriminated against using the flight-time technique. No collimators or shielding are required, the neutron generator is relatively small, and commercial-grade electronics are employed. The use of 14-MeV neutrons yields a much higher cross-section for detecting nitrogen than that for systems based on thermal-neutron reactions alone, and the broad range of elements with significant 14-MeV neutron cross-sections extends explosives detection to other elements including low-nitrogen compounds, and allows detection of many other substances. Proof-of-concept experiments have been successfully performed for conventional explosives, chemical warfare agents, cocaine, and fissionable materials.

  19. Evaluation of the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing.

    PubMed

    Ferrari, Robert

    2015-09-01

    The objective of this study was to evaluate the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing. Patients with joint pain/stiffness/swelling were assessed to determine if ANA testing was indicated. An a priori threshold was set before ANA testing would be considered. Those who did not have ANA testing ordered were followed for 1 year to determine if any of them went on to have a diagnosis of systemic lupus erythematosus (SLE) or other connective tissue disease. A parallel study was conducted with a similar a priori threshold for the use of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody testing in the diagnosis of rheumatoid arthritis (RA), and again, patients were followed for 1 year. A total of 866 subjects were examined, 509 females (58.8 %) and 357 males (41.2 %). The mean age of the group was 47.5 ± 16.8 years. The mean duration of symptoms was 12.0 ± 5.6 weeks. Of the 866 subjects, 68 met an a priori threshold for ordering ANA, RF, and anti-CCP testing. Of these 68, there was a newly diagnosed case of SLE, 4 newly diagnosed cases of RA, and 3 cases of polymyalgia rheumatica. The remaining 798 subjects were followed for approximately 1 year and none developed evidence of SLE, RA, or other connective tissue disease. In the evaluation of non-specific musculoskeletal symptoms, setting an a priori threshold for ordering serology in keeping with the spirit of the Canadian Rheumatology Association Choosing Wisely recommendation for antibody testing results in a very low risk of missing a case of systemic lupus erythematosus or rheumatoid arthritis.

  20. Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix- associated PML bodies

    PubMed Central

    1995-01-01

    The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells due to the expression of the PML-RAR alpha hybrid. Here we report that adenovirus infection causes a drastic redistribution of PML from spherical nuclear bodies into fibrous structures. The product encoded by adenovirus E4- ORF3 is shown to be responsible for this reorganization and to colocalize with PML into these fibers. In addition, we demonstrate that E1A oncoproteins concentrate in the PML domains, both in infected and transiently transfected cells, and that this association requires the conserved amino acid motif (D)LXCXE, common to all viral oncoproteins that bind pRB or the related p107 and p130 proteins. The SV-40 large T antigen, another member of this oncoprotein family is also found in close association with the PML nuclear bodies. Taken together, the present data indicate that the subnuclear domains containing PML represent a preferential target for DNA tumor viruses, and therefore suggest a more general involvement of the PML nuclear bodies in oncogenic processes. PMID:7559785

  1. Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function

    PubMed Central

    2011-01-01

    Background Central to the fully competent replication cycle of the human immunodeficiency virus type 1 (HIV-1) is the nuclear export of unspliced and partially spliced RNAs mediated by the Rev posttranscriptional activator and the Rev response element (RRE). Results Here, we introduce a novel method to explore the proteome associated with the nuclear HIV-1 RNAs. At the core of the method is the generation of cell lines harboring an integrated provirus carrying RNA binding sites for the MS2 bacteriophage protein. Flag-tagged MS2 is then used for affinity purification of the viral RNA. By this approach we found that the viral RNA is associated with the host nuclear matrix component MATR3 (Matrin 3) and that its modulation affected Rev activity. Knockdown of MATR3 suppressed Rev/RRE function in the export of unspliced HIV-1 RNAs. However, MATR3 was able to associate with Rev only through the presence of RRE-containing viral RNA. Conclusions In this work, we exploited a novel proteomic method to identify MATR3 as a cellular cofactor of Rev activity. MATR3 binds viral RNA and is required for the Rev/RRE mediated nuclear export of unspliced HIV-1 RNAs. PMID:21771346

  2. Three-Dimensional Visualization of Transcription Sites and Their Association with Splicing Factor–Rich Nuclear Speckles

    PubMed Central

    Wei, Xiangyun; Somanathan, Suryanarayan; Samarabandu, Jagath; Berezney, Ronald

    1999-01-01

    Transcription sites are detected by labeling nascent transcripts with BrUTP in permeabilized 3T3 mouse fibroblasts followed by laser scanning confocal microscopy. Inhibition and enzyme digestion studies confirm that the labeled sites are from RNA transcripts and that RNA polymerase I (RP I) and II (RP II) are responsible for nucleolar and extranucleolar transcription, respectively. An average of 2,000 sites are detected per nucleus with over 90% in the extranucleolar compartment where they are arranged in clusters and three-dimensional networklike arrays. The number of transcription sites, their three-dimensional organization and arrangement into functional zones (Wei et al. 1998) is strikingly maintained after extraction for nuclear matrix. Significant levels of total RP II mediated transcription sites (45%) were associated with splicing factor–rich nuclear speckles even though the speckles occupied <10% of the total extranucleolar space. Moreover, the vast majority of nuclear speckles (>90%) had moderate to high levels of associated transcription activity. Transcription sites were found along the periphery as well as inside the speckles themselves. These spatial relations were confirmed in optical sections through individual speckles and after in vivo labeling of nascent transcripts. Our results demonstrate that nuclear speckles and their surrounding regions are major sites of RP II-mediated transcription in the cell nucleus, and support the view that both speckle- and nonspeckle-associated regions of the nucleus contain sites for the coordination of transcription and splicing processes. PMID:10444064

  3. Atmospheric release advisory capability pilot project at two nuclear power plants and associated state offices of emergency preparedness. Final report

    SciTech Connect

    Rosen, L.C.

    1983-01-01

    A project to demonstrate the feasibility of utilizing Atmospheric Release Advisory Capability (ARAC) limited service with commercial nuclear power plants and their associated state offices of emergency preparedness is discussed. Preliminary planning, installation and testing of the ARAC site facilities at Indian Point Nucler Power Station, New York State; at New York State Office of Emergency Preparedness, Albany, New York; at Rancho Seco Nuclear Generating Station, California; and at the State of California Office of Emergency Services, Sacramento, California, are summarized. ARAC participation in the Robert E. Ginna nuclear generating plant accident in New York on January 25, 1982, is discussed. The ARAC system is evaluated with emphasis on communications, the suite of models contained within the ARAC system, and the staff. The implications of this project in designing the next-generation ARAC system to service federal and state needs are assessed.

  4. GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes.

    PubMed Central

    Elefanty, A G; Antoniou, M; Custodio, N; Carmo-Fonseca, M; Grosveld, F G

    1996-01-01

    The nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse nucleoplasmic localization. These foci, which were preferentially found adjacent to nucleoli or at the nuclear periphery, did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci. Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence. The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous (Spl, c-Jun and TBP) or haemopoietic (NF-E2) transcription factors. Interestingly, GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA-1 and -2 or GATA-1 and -3 gene products. This pattern of distribution is, thus far, unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain. Images PMID:8617207

  5. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects.

    PubMed

    Hashizume, Osamu; Ohnishi, Sakiko; Mito, Takayuki; Shimizu, Akinori; Ishikawa, Kaori; Iashikawa, Kaori; Nakada, Kazuto; Soda, Manabu; Mano, Hiroyuki; Togayachi, Sumie; Miyoshi, Hiroyuki; Okita, Keisuke; Hayashi, Jun-Ichi

    2015-05-22

    Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. We carried out reprogramming of human fibroblast lines derived from elderly subjects by generating their induced pluripotent stem cells (iPSCs), and examined another possibility, namely that these aging phenotypes are controlled not by mutations but by epigenetic regulation. Here, we show that reprogramming of elderly fibroblasts restores age-associated mitochondrial respiration defects, indicating that these aging phenotypes are reversible and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either the nuclear or the mitochondrial genome. Microarray screening revealed that epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes.

  6. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects

    PubMed Central

    Hashizume, Osamu; Ohnishi, Sakiko; Mito, Takayuki; Shimizu, Akinori; Ishikawa, Kaori; Nakada, Kazuto; Soda, Manabu; Mano, Hiroyuki; Togayachi, Sumie; Miyoshi, Hiroyuki; Okita, Keisuke; Hayashi, Jun-Ichi

    2015-01-01

    Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. We carried out reprogramming of human fibroblast lines derived from elderly subjects by generating their induced pluripotent stem cells (iPSCs), and examined another possibility, namely that these aging phenotypes are controlled not by mutations but by epigenetic regulation. Here, we show that reprogramming of elderly fibroblasts restores age-associated mitochondrial respiration defects, indicating that these aging phenotypes are reversible and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either the nuclear or the mitochondrial genome. Microarray screening revealed that epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes. PMID:26000717

  7. NRP/B, a Novel Nuclear Matrix Protein, Associates With p110RB and Is Involved in Neuronal Differentiation

    PubMed Central

    Kim, Tae-Aug; Lim, Jinkyu; Ota, Setsuo; Raja, Sandhya; Rogers, Rick; Rivnay, Benjamin; Avraham, Hava; Avraham, Shalom

    1998-01-01

    The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain–like structure in the predicted NH2 terminus, and a “kelch motif” in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110RB) is found to be associated with the nuclear matrix and overexpression of p110RB induces neuronal differentiation, we investigated whether NRP/B is associated with p110RB. Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110RB during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110RB and participates in the regulation of neuronal process formation. PMID:9566959

  8. Issues Associated with IAEA Involvement in Assured Nuclear Fuel Supply Arrangements

    SciTech Connect

    Kessler, Carol E.; Mathews, Carrie E.

    2008-02-08

    Assured nuclear fuel supply has been discussed at various times as a mechanism to help limit expansion of enrichment and reprocessing (E&R) capability beyond current technology holders. Given the events in the last few years in North Korea and Iran, concern over weapons capabilities gained from acquisition of E&R capabilities has heightened and brought assured nuclear fuel supply (AFS) again to the international agenda. Successful AFS programs can be valuable contributions to strengthening the nonproliferation regime and helping to build public support for expanding nuclear energy.

  9. [Clinical phenotypes of hepatocyte nuclear factor 1 homeobox b-associated disease].

    PubMed

    Wang, F; Yao, Y; Yang, H X; Shi, C Y; Zhang, X X; Xiao, H J; Zhang, H W; Su, B G; Zhang, Y Q; Guo, J F; Ding, J

    2017-09-02

    Objective: Hepatocyte nuclear factor 1 homeobox b (HNF1B) -associated disease is an autosomal dominant inherited disorder with a variable, multi-systemic phenotype. In China, five adult probands and one child proband with HNF1B-associated disease had been reported, whereas few fetuses are described. The aims of this retrospective study were to understand about the clinical manifestations of HNF1B-associated disease and to further improve the recognition of this disorder. Method: Four patients (3 males, 1 female) and three fetuses with HNF1B mutations were included in this study. They were admitted to our hospital from January 2013 to March 2017. HNF1B mutations were detected using targeted next generation sequencing and quantitative real-time PCR or Sanger sequencing. HNF1B heterozygous deletion of exons 1-9 was found in 4 patients and 2 fetuses, and HNF1B heterozygous missense mutation in 1 fetus. These two mutations had been reported. Two patients and 1 fetus had de novo mutations. Results of renal ultrasonography with or without magnetic resonance imaging, biochemical investigations, urine routine examination and other necessary investigations in 7 cases were analyzed. Result: Three patients were Han Chinese ethnicity, and one patient was Mongolian. In patients 1 and 4, abnormal fetal kidneys were discovered by routine ultrasonography, and the age at first feature identified in Patients 2 and 3 were 13 years and 28 years. Patient 3 had normal renal function and the remainder had reduced glomerular filtration rate. In addition, patient 4 presented with nephrotic syndrome and glycosuria, patient 2 with early onset hyperparathyroidism and renal osteodystrophy, and patient 3 with diabetes mellitus. All the 4 patients had renal structural abnormalities including bilateral multiple renal cysts, dysplasia and hyperechogenic kidneys. Only patient 3 had a positive family history of renal diseases, the remainder had a negative family history of renal diseases. In 3

  10. Magnesium Presence Prevents Removal of Antigenic Nuclear-Associated Proteins from Bovine Pericardium for Heart Valve Engineering.

    PubMed

    Dalgliesh, Ailsa J; Liu, Zhi Zhao; Griffiths, Leigh G

    2017-03-10

    Current heart valve prostheses are associated with significant complications, including aggressive immune response, limited valve life expectancy, and inability to grow in juvenile patients. Animal derived "tissue" valves undergo glutaraldehyde fixation to mask tissue antigenicity; however, chronic immunological responses and associated calcification still commonly occur. A heart valve formed from an unfixed bovine pericardium (BP) extracellular matrix (ECM) scaffold, in which antigenic burden has been eliminated or significantly reduced, has potential to overcome deficiencies of current bioprostheses. Decellularization and antigen removal methods frequently use sequential solutions extrapolated from analytical chemistry approaches to promote solubility and removal of tissue components from resultant ECM scaffolds. However, the extent to which such prefractionation strategies may inhibit removal of antigenic tissue components has not been explored. We hypothesize that presence of magnesium in prefractionation steps causes DNA precipitation and reduces removal of nuclear-associated antigenic proteins. Keeping all variables consistent bar the addition or absence of magnesium (2 mM magnesium chloride hexahydrate), residual BP ECM scaffold antigenicity and removed antigenicity were assessed, along with residual and removed DNA content, ECM morphology, scaffold composition, and recellularization potential. Furthermore, we used proteomic methods to determine the mechanism by which magnesium presence or absence affects scaffold residual antigenicity. This study demonstrates that absence of magnesium from antigen removal solutions enhances solubility and subsequent removal of antigenic nuclear-associated proteins from BP. We therefore conclude that the primary mechanism of action for magnesium removal during antigen removal processes is avoidance of DNA precipitation, facilitating solubilization and removal of nuclear-associated antigenic proteins. Future studies are

  11. Identification and characterisation of a nuclear localisation signal in the SMN associated protein, Gemin4

    SciTech Connect

    Lorson, Monique A.; Dickson, Alexa M.; Shaw, Debra J.; Todd, Adrian G.; Young, Elizabeth C.; Morse, Robert; Wolstencroft, Catherine; Lorson, Christian L.; Young, Philip J.

    2008-10-10

    Gemin4 is a ubiquitously expressed multifunctional protein that is involved in U snRNP assembly, apoptosis, nuclear/cytoplasmic transportation, transcription, and RNAi pathways. Gemin4 is one of the core components of the Gemin-complex, which also contains survival motor neuron (SMN), the seven Gemin proteins (Gemin2-8), and Unrip. Mutations in the SMN1 gene cause the autosomal recessive disorder spinal muscular atrophy (SMA). Although the functions assigned to Gemin4 predominantly occur in the nucleus, the mechanisms that mediate the nuclear import of Gemin4 remain unclear. Here, using a novel panel of Gemin4 constructs we identify a canonical nuclear import sequence (NLS) in the N-terminus of Gemin4. The Gemin4 NLS is necessary and independently sufficient to mediate nuclear import of Gemin4. This is the first functional NLS identified within the SMN-Gemin complex.

  12. REG-γ associates with and modulates the abundance of nuclear activation-induced deaminase

    PubMed Central

    Uchimura, Yasuhiro; Barton, Lance F.; Rada, Cristina

    2011-01-01

    Activation-induced deaminase (AID) acts on the immunoglobulin loci in activated B lymphocytes to initiate antibody gene diversification. The abundance of AID in the nucleus appears tightly regulated, with most nuclear AID being either degraded or exported back to the cytoplasm. To gain insight into the mechanisms regulating nuclear AID, we screened for proteins interacting specifically with it. We found that REG-γ, a protein implicated in ubiquitin- and ATP-independent protein degradation, interacts in high stoichiometry with overexpressed nuclear AID as well as with endogenous AID in B cells. REG-γ deficiency results in increased AID accumulation and increased immunoglobulin class switching. A stable stoichiometric AID–REG-γ complex can be recapitulated in co-transformed bacteria, and REG-γ accelerates proteasomal degradation of AID in in vitro assays. Thus, REG-γ interacts, likely directly, with nuclear AID and modulates the abundance of this antibody-diversifying but potentially oncogenic enzyme. PMID:22042974

  13. Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring

    PubMed Central

    Ke, Yao-hua; Xiao, Wen-jin; He, Jin-wei; Zhang, Hao; Yu, Jin-bo; Hu, Wei-wei; Gu, Jie-mei; Gao, Gao; Yue, Hua; Wang, Chun; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Fu, Wen-zhen; Zhang, Zhen-lin

    2012-01-01

    Aim: Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese nuclear families with male offspring. Methods: We recruited 1,296 subjects from 427 nuclear families with male offspring and genotyped five SNPs (rs9894225, rs748694, rs2619112, rs2619118, and rs916055) in the ALOX15 gene locus. The total fat mass (TFM), trunk fat mass (tFM), leg fat mass (LFM) and arm fat mass (AFM) were measured using dual-energy X-ray absorptiometry (DXA). The percentage of fat mass (PFM) was the ratio of TFM and body weight. The association between SNPs and haplotypes of ALOX15 and obesity-related phenotypic variation was measured using quantitative transmission disequilibrium test (QTDT). Results: Using QTDT to measure family-based genetic association, we found that rs916055 had a statistically significant association with PFM (P=0.038), whereas rs916055 had a marginal but statistically insignificant association with tFM (P=0.093). The multiple-parameter 1000 permutations test agreed with the family-based association results: both showed that rs916055 had a statistically significant association with PFM (P=0.033). Conclusion: rs916055 in ALOX15 gene was significantly associated with the percentage of fat mass in Chinese nuclear families with male offspring in the family-based association study using QTDT approach. PMID:22301860

  14. Muscular dystrophy-associated SUN1 and SUN2 variants disrupt nuclear-cytoskeletal connections and myonuclear organization.

    PubMed

    Meinke, Peter; Mattioli, Elisabetta; Haque, Farhana; Antoku, Susumu; Columbaro, Marta; Straatman, Kees R; Worman, Howard J; Gundersen, Gregg G; Lattanzi, Giovanna; Wehnert, Manfred; Shackleton, Sue

    2014-09-01

    Proteins of the nuclear envelope (NE) are associated with a range of inherited disorders, most commonly involving muscular dystrophy and cardiomyopathy, as exemplified by Emery-Dreifuss muscular dystrophy (EDMD). EDMD is both genetically and phenotypically variable, and some evidence of modifier genes has been reported. Six genes have so far been linked to EDMD, four encoding proteins associated with the LINC complex that connects the nucleus to the cytoskeleton. However, 50% of patients have no identifiable mutations in these genes. Using a candidate approach, we have identified putative disease-causing variants in the SUN1 and SUN2 genes, also encoding LINC complex components, in patients with EDMD and related myopathies. Our data also suggest that SUN1 and SUN2 can act as disease modifier genes in individuals with co-segregating mutations in other EDMD genes. Five SUN1/SUN2 variants examined impaired rearward nuclear repositioning in fibroblasts, confirming defective LINC complex function in nuclear-cytoskeletal coupling. Furthermore, myotubes from a patient carrying compound heterozygous SUN1 mutations displayed gross defects in myonuclear organization. This was accompanied by loss of recruitment of centrosomal marker, pericentrin, to the NE and impaired microtubule nucleation at the NE, events that are required for correct myonuclear arrangement. These defects were recapitulated in C2C12 myotubes expressing exogenous SUN1 variants, demonstrating a direct link between SUN1 mutation and impairment of nuclear-microtubule coupling and myonuclear positioning. Our findings strongly support an important role for SUN1 and SUN2 in muscle disease pathogenesis and support the hypothesis that defects in the LINC complex contribute to disease pathology through disruption of nuclear-microtubule association, resulting in defective myonuclear positioning.

  15. Muscular Dystrophy-Associated SUN1 and SUN2 Variants Disrupt Nuclear-Cytoskeletal Connections and Myonuclear Organization

    PubMed Central

    Antoku, Susumu; Columbaro, Marta; Straatman, Kees R.; Worman, Howard J.; Gundersen, Gregg G.; Lattanzi, Giovanna; Wehnert, Manfred; Shackleton, Sue

    2014-01-01

    Proteins of the nuclear envelope (NE) are associated with a range of inherited disorders, most commonly involving muscular dystrophy and cardiomyopathy, as exemplified by Emery-Dreifuss muscular dystrophy (EDMD). EDMD is both genetically and phenotypically variable, and some evidence of modifier genes has been reported. Six genes have so far been linked to EDMD, four encoding proteins associated with the LINC complex that connects the nucleus to the cytoskeleton. However, 50% of patients have no identifiable mutations in these genes. Using a candidate approach, we have identified putative disease-causing variants in the SUN1 and SUN2 genes, also encoding LINC complex components, in patients with EDMD and related myopathies. Our data also suggest that SUN1 and SUN2 can act as disease modifier genes in individuals with co-segregating mutations in other EDMD genes. Five SUN1/SUN2 variants examined impaired rearward nuclear repositioning in fibroblasts, confirming defective LINC complex function in nuclear-cytoskeletal coupling. Furthermore, myotubes from a patient carrying compound heterozygous SUN1 mutations displayed gross defects in myonuclear organization. This was accompanied by loss of recruitment of centrosomal marker, pericentrin, to the NE and impaired microtubule nucleation at the NE, events that are required for correct myonuclear arrangement. These defects were recapitulated in C2C12 myotubes expressing exogenous SUN1 variants, demonstrating a direct link between SUN1 mutation and impairment of nuclear-microtubule coupling and myonuclear positioning. Our findings strongly support an important role for SUN1 and SUN2 in muscle disease pathogenesis and support the hypothesis that defects in the LINC complex contribute to disease pathology through disruption of nuclear-microtubule association, resulting in defective myonuclear positioning. PMID:25210889

  16. The Small Nuclear Genomes of Selaginella Are Associated with a Low Rate of Genome Size Evolution.

    PubMed

    Baniaga, Anthony E; Arrigo, Nils; Barker, Michael S

    2016-06-03

    The haploid nuclear genome size (1C DNA) of vascular land plants varies over several orders of magnitude. Much of this observed diversity in genome size is due to the proliferation and deletion of transposable elements. To date, all vascular land plant lineages with extremely small nuclear genomes represent recently derived states, having ancestors with much larger genome sizes. The Selaginellaceae represent an ancient lineage with extremely small genomes. It is unclear how small nuclear genomes evolved in Selaginella We compared the rates of nuclear genome size evolution in Selaginella and major vascular plant clades in a comparative phylogenetic framework. For the analyses, we collected 29 new flow cytometry estimates of haploid genome size in Selaginella to augment publicly available data. Selaginella possess some of the smallest known haploid nuclear genome sizes, as well as the lowest rate of genome size evolution observed across all vascular land plants included in our analyses. Additionally, our analyses provide strong support for a history of haploid nuclear genome size stasis in Selaginella Our results indicate that Selaginella, similar to other early diverging lineages of vascular land plants, has relatively low rates of genome size evolution. Further, our analyses highlight that a rapid transition to a small genome size is only one route to an extremely small genome.

  17. The Small Nuclear Genomes of Selaginella Are Associated with a Low Rate of Genome Size Evolution

    PubMed Central

    Baniaga, Anthony E.; Arrigo, Nils; Barker, Michael S.

    2016-01-01

    The haploid nuclear genome size (1C DNA) of vascular land plants varies over several orders of magnitude. Much of this observed diversity in genome size is due to the proliferation and deletion of transposable elements. To date, all vascular land plant lineages with extremely small nuclear genomes represent recently derived states, having ancestors with much larger genome sizes. The Selaginellaceae represent an ancient lineage with extremely small genomes. It is unclear how small nuclear genomes evolved in Selaginella. We compared the rates of nuclear genome size evolution in Selaginella and major vascular plant clades in a comparative phylogenetic framework. For the analyses, we collected 29 new flow cytometry estimates of haploid genome size in Selaginella to augment publicly available data. Selaginella possess some of the smallest known haploid nuclear genome sizes, as well as the lowest rate of genome size evolution observed across all vascular land plants included in our analyses. Additionally, our analyses provide strong support for a history of haploid nuclear genome size stasis in Selaginella. Our results indicate that Selaginella, similar to other early diverging lineages of vascular land plants, has relatively low rates of genome size evolution. Further, our analyses highlight that a rapid transition to a small genome size is only one route to an extremely small genome. PMID:27189987

  18. Analysis of the formation, expression, and economic impacts of risk perceptions associated with nuclear facilities

    SciTech Connect

    Allison, T.; Hunter, S.; Calzonetti, F.J.

    1992-10-01

    This report investigates how communities hosting nuclear facilities form and express perceptions of risk and how these risk perceptions affect local economic development. Information was collected from site visits and interviews with plant personnel, officials of local and state agencies, and community activists in the hosting communities. Six commercial nuclear fuel production facilities and five nuclear facilities operated for the US Department of Energy by private contractors were chosen for analysis. The results presented in the report indicate that the nature of risk perceptions depends on a number of factors. These factors are (1) level of communication by plant officials within the local community, (2) track record of the facility. operator, (3) process through which community and state officials receive information and form opinions, (4) level of economic links each plant has with the local community, and (15) physical characteristics of the facility itself. This report finds that in the communities studied, adverse ask perceptions have not affected business location decisions, employment levels in the local community, tourism, or agricultural development. On the basis of case-study findings, this report recommends that nuclear facility siting programs take the following observations into account when addressing perceptions of risk. First, the quality of a facility`s participation with community activists, interest groups, and state agencies helps to determine the level of perceived risk within a community. Second, the development of strong economic links between nuclear facilities and their host communities will produce a higher level of acceptance of the nuclear facilities.

  19. STS-107 Mission Specialist David Brown suits up for TCDT

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- STS-107 Mission Specialist David Brown waves as he completes suit check prior to Terminal Countdown Demonstration Test activities, which include a simulated launch countdown at the pad. STS-107 is a mission devoted to research and will include more than 80 experiments that will study Earth and space science, advanced technology development, and astronaut health and safety. Launch is planned for Jan. 16, 2003, between 10 a.m. and 2 p.m. EST aboard Space Shuttle Columbia. .

  20. David Kasner, MD, and the Road to Pars Plana Vitrectomy

    PubMed Central

    Blodi, Christopher F.

    2016-01-01

    David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

  1. Astronaut S. David Griggs waves to Orbiter during EVA

    NASA Image and Video Library

    1985-04-16

    51D-04-025 (16 April 1985) --- Bearing a maze of interesting reflections, this aquarium-like scene came during one of the lighter moments of emergency extravehicular activity (EVA) aboard the Earth-orbiting Space Shuttle Discovery. Astronaut S. David Griggs, waving from the cargo bay into the flight deck, earlier participated with astronaut Jeffrey A. Hoffman in the successful attachment of two special tools to the end of the Canadian-built Remote Manipulator System (RMS) arm. The Earth's horizon appears both in the background of the scene and in the reflection in Griggs' helmet visor.

  2. Novel Problems Associated with Accounting and Control of Nuclear Material from Decontamination and Decommissioning and in Waste

    SciTech Connect

    Schlegel, Steven C.

    2007-07-10

    Abstract The reduction in nuclear arms and the production facilities that supported the weapons programs have produced some unique problems for nuclear material control and accountability (MC&A). Many of these problems are not limited to the weapons complex, but have the potential to appear in many legacy facilities as they undergo dismantlement and disposal. Closing facilities find that what was previously defined as product has become a waste stream bringing regulatory, human, and technological conflict. The sometimes unique compositions of these materials produce both storage and measurement problems. The nuclear material accounting and control programs have had to become very adaptive and preemptive to ensure control and protection is maintained. This paper examines some of the challenges to Safeguards generated by deinventory, decontamination decommissioning, dismantlement, demolition, and waste site remediation from predictable sources and some from unpredictable sources. 1.0 Introduction The United States is eliminating many facilities that support the nuclear weapons program. With the changing political conditions around the world and changes in military capabilities, the decreased emphasis on nuclear weapons has eliminated the need for many of the aging facilities. Additionally, the recovery of plutonium from dismantled weapons and reuse of components has eliminated the need to produce more plutonium for the near future. Because the nuclear weapons program and commercial applications generally do not mix in the United States, the facilities in the DOE complex that no longer have a weapon mission are being deinventoried, decontaminated, decommissioned, and dismantled/demolished. The materials from these activities are then disposed of in various ways but usually in select waste burial sites. Additionally, the waste in many historical burial sites associated with the weapons complex are being recovered, repackaged if necessary, and disposed of in either

  3. Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (KSHV) upregulates survivin expression in KSHV-Associated B-lymphoma cells and contributes to their proliferation.

    PubMed

    Lu, Jie; Verma, Subhash C; Murakami, Masanao; Cai, Qiliang; Kumar, Pankaj; Xiao, Bingyi; Robertson, Erle S

    2009-07-01

    Survivin is a master regulator of cell proliferation and cell viability and is highly expressed in most human tumors. The molecular network linked to survivin expression in tumors has not been completely elucidated. In this study, we show that latency-associated nuclear antigen (LANA), a multifunctional protein of Kaposi's sarcoma-associated herpesvirus (KSHV) that is found in Kaposi's sarcoma tumors, upregulates survivin expression and increases the proliferation of KSHV-infected B cells. Analysis of pathway-specific gene arrays showed that survivin expression was highly upregulated in BJAB cells expressing LANA. The mRNA levels of survivin were also upregulated in HEK 293 and BJAB cells expressing LANA. Similarly, protein levels of survivin were significantly higher in LANA-expressing, as well as KSHV-infected, cells. Survivin promoter activity assays identified GC/Sp1 and p53 cis-acting elements within the core promoter region as being important for LANA activity. Gel mobility shift assays revealed that LANA forms a complex with Sp1 or Sp1-like proteins bound to the GC/Sp1 box of the survivin promoter. In addition, a LANA/p53 complex bound to the p53 cis-acting element within the survivin promoter, indicating that upregulation of survivin expression can also occur through suppression of p53 function. Furthermore, immunohistochemistry analyses revealed that survivin expression was upregulated in KSHV-associated Kaposi's sarcoma tissue, suggesting that LANA plays an important role in the upregulation of survivin expression in KSHV-infected endothelial cells. Knockdown of survivin expression by lentivirus-delivered small hairpin RNA resulted in loss of cell proliferation in KSHV-infected cells. Therefore, upregulation of survivin expression in KSHV-associated human cells contributes to their proliferation.

  4. The Role of Nuclear Medicine in the Staging and Management of Human Immune Deficiency Virus Infection and Associated Diseases.

    PubMed

    Ankrah, Alfred O; Glaudemans, Andor W J M; Klein, Hans C; Dierckx, Rudi A J O; Sathekge, Mike

    2017-06-01

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  5. Decreased Expression of Nuclear p300 Is Associated with Disease Progression and Worse Prognosis of Melanoma Patients

    PubMed Central

    Rotte, Anand; Bhandaru, Madhuri; Cheng, Yabin; Sjoestroem, Cecilia; Martinka, Magdalena; Li, Gang

    2013-01-01

    Background Genomic instability due to UV radiation is one of the leading causes for melanoma. Histone acetyltransferase p300 plays an indispensible role in DNA repair and maintenance of genomic integrity. The present study was performed to analyze the correlation between p300 expression, melanoma progression and patient survival. Methods Tissue microarray and immunohistochemical analysis was employed to study the expression of p300 in melanoma patients. A total of 358 melanoma patients (250 primary melanoma and 108 metastatic melanoma) were used for the study. Kaplan-Meier, univariate and multivariate Cox regression analysis, and receiver-operating characteristic curves, were used to elucidate the prognostic significance of p300 expression. Results Our results demonstrate that p300 is expressed in both nucleus and cytoplasm but the nuclear expression of p300 is predominant. The progression of disease from dysplastic nevi to primary melanoma and to metastatic melanoma was associated with decreased nuclear and increased cytoplasmic p300 expression. Especially, the loss of nuclear and gain in cytoplasmic p300 was correlated with the progression of melanoma from AJCC stage II to stage III, which requires the migration and metastasis of cancer cells from primary sites to lymph nodes. Similarly, decrease in nuclear, and increase in cytoplasmic p300 expression correlated with worse survival of melanoma patients. Nuclear p300 but not cytoplasmic p300 could predict the patient survival independent of AJCC stage, age and gender. Conclusion Loss of nuclear p300 expression is an indicator of worse patient survival and is an independent prognostic marker for melanoma. PMID:24098694

  6. Nitric oxide induces thioredoxin-1 nuclear translocation: Possible association with the p21Ras survival pathway

    SciTech Connect

    Arai, Roberto J.; Yodoi, J.; Debbas, V.; Laurindo, Francisco R.; Stern, A.; Monteiro, Hugo P. . E-mail: hpmonte@uol.com.br

    2006-10-06

    One of the major redox-regulating molecules with thiol reducing activity is thioredoxin-1 (TRX-1). TRX-1 is a multifunctional protein that exists in the extracellular millieu, cytoplasm, and nucleus, and has a distinct role in each environment. It is well known that TRX-1 promptly migrates to the nuclear compartment in cells exposed to oxidants. However, the intracellular location of TRX-1 in cells exposed to nitrosothiols has not been investigated. Here, we demonstrated that the exposure of HeLa cells to increasing concentrations of the nitrosothiol S-nitroso-N-acetylpenicillamine (SNAP) promoted TRX-1 nuclear accumulation. The SNAP-induced TRX-1 translocation to the nucleus was inhibited by FPTIII, a selective inhibitor of p21Ras. Furthermore, TRX-1 migration was attenuated in cells stably transfected with NO insensitive p21Ras (p21{sup RasC118S}). Downstream to p21Ras, the MAP Kinases ERK1/2 were activated by SNAP under conditions that promote TRX-1 nuclear translocation. Inhibition of MEK prevented SNAP-stimulated ERK1/2 activation and TRX-1 nuclear migration. In addition, cells treated with p21Ras or MEK inhibitor showed increased susceptibility to cell death induced by SNAP. In conclusion, our observations suggest that the nuclear translocation of TRX-1 is induced by SNAP involving p21Ras survival pathway.

  7. Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

    PubMed

    Can, Nuray; Celik, Mehmet; Sezer, Yavuz Atakan; Ozyilmaz, Filiz; Ayturk, Semra; Tastekin, Ebru; Sut, Necdet; Gurkan, Hakan; Ustun, Funda; Bulbul, Buket Yilmaz; Guldiken, Sibel; Puyan, Fulya Oz

    2017-08-20

    The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

  8. The GIP gamma-tubulin complex-associated proteins are involved in nuclear architecture in Arabidopsis thaliana

    PubMed Central

    Batzenschlager, Morgane; Masoud, Kinda; Janski, Natacha; Houlné, Guy; Herzog, Etienne; Evrard, Jean-Luc; Baumberger, Nicolas; Erhardt, Mathieu; Nominé, Yves; Kieffer, Bruno; Schmit, Anne-Catherine; Chabouté, Marie-Edith

    2013-01-01

    During interphase, the microtubular cytoskeleton of cycling plant cells is organized in both cortical and perinuclear arrays. Perinuclear microtubules (MTs) are nucleated from γ-Tubulin Complexes (γ-TuCs) located at the surface of the nucleus. The molecular mechanisms of γ-TuC association to the nuclear envelope (NE) are currently unknown. The γ-TuC Protein 3 (GCP3)-Interacting Protein 1 (GIP1) is the smallest γ-TuC component identified so far. AtGIP1 and its homologous protein AtGIP2 participate in the localization of active γ-TuCs at interphasic and mitotic MT nucleation sites. Arabidopsis gip1gip2 mutants are impaired in establishing a fully functional mitotic spindle and exhibit severe developmental defects. In this study, gip1gip2 knock down mutants were further characterized at the cellular level. In addition to defects in both the localization of γ-TuC core proteins and MT fiber robustness, gip1gip2 mutants exhibited a severe alteration of the nuclear shape associated with an abnormal distribution of the nuclear pore complexes. Simultaneously, they showed a misorganization of the inner nuclear membrane protein AtSUN1. Furthermore, AtGIP1 was identified as an interacting partner of AtTSA1 which was detected, like the AtGIP proteins, at the NE. These results provide the first evidence for the involvement of a γ-TuC component in both nuclear shaping and NE organization. Functional hypotheses are discussed in order to propose a model for a GIP-dependent nucleo-cytoplasmic continuum. PMID:24348487

  9. The GIP gamma-tubulin complex-associated proteins are involved in nuclear architecture in Arabidopsis thaliana.

    PubMed

    Batzenschlager, Morgane; Masoud, Kinda; Janski, Natacha; Houlné, Guy; Herzog, Etienne; Evrard, Jean-Luc; Baumberger, Nicolas; Erhardt, Mathieu; Nominé, Yves; Kieffer, Bruno; Schmit, Anne-Catherine; Chabouté, Marie-Edith

    2013-01-01

    During interphase, the microtubular cytoskeleton of cycling plant cells is organized in both cortical and perinuclear arrays. Perinuclear microtubules (MTs) are nucleated from γ-Tubulin Complexes (γ-TuCs) located at the surface of the nucleus. The molecular mechanisms of γ-TuC association to the nuclear envelope (NE) are currently unknown. The γ-TuC Protein 3 (GCP3)-Interacting Protein 1 (GIP1) is the smallest γ-TuC component identified so far. AtGIP1 and its homologous protein AtGIP2 participate in the localization of active γ-TuCs at interphasic and mitotic MT nucleation sites. Arabidopsis gip1gip2 mutants are impaired in establishing a fully functional mitotic spindle and exhibit severe developmental defects. In this study, gip1gip2 knock down mutants were further characterized at the cellular level. In addition to defects in both the localization of γ-TuC core proteins and MT fiber robustness, gip1gip2 mutants exhibited a severe alteration of the nuclear shape associated with an abnormal distribution of the nuclear pore complexes. Simultaneously, they showed a misorganization of the inner nuclear membrane protein AtSUN1. Furthermore, AtGIP1 was identified as an interacting partner of AtTSA1 which was detected, like the AtGIP proteins, at the NE. These results provide the first evidence for the involvement of a γ-TuC component in both nuclear shaping and NE organization. Functional hypotheses are discussed in order to propose a model for a GIP-dependent nucleo-cytoplasmic continuum.

  10. Attitudes of Mississippi college students toward David Duke before and after seeing the film Who is David Duke?

    PubMed

    Eisenman, R; Girdner, E J; Burroughs, R G; Routman, M

    1993-01-01

    The attitudes of 211 students at a university in Mississippi were investigated both before and after seeing the Public Broadcasting Film Who Is David Duke? The film provided evidence of Duke's current racism, anti-Semitism, and pro-Nazi leanings. In a previous study with university students in Louisiana, the majority did not change their attitudes after watching the film (Eisenman, 1993). However, in the present study, students' attitudes showed change in an anti-Duke direction. The findings are discussed and reasons given for the differences between the two samples, and for the popularity of Duke, a former leader of the Ku Klux Klan.

  11. High expression of the Epstein-Barr virus latent protein EB nuclear antigen-2 on pyothorax-associated lymphomas.

    PubMed Central

    Sasajima, Y.; Yamabe, H.; Kobashi, Y.; Hirai, K.; Mori, S.

    1993-01-01

    Pyothorax-associated lymphoma (PAL) is a rare tumor associated with long-standing tuberculous pyothorax. Most of these lymphomas are B-cell lymphomas of high-grade malignancy. Over 50 cases have been reported in Japan, but no cases have been described in Western countries. Its pathogenesis remains unknown. We studied immunohistologically the expression of Epstein-Barr virus- (EBV) encoded latent gene products, EB nuclear antigen-2 and LMP-1, in four cases of PAL. Fifty B-cell lymphomas unrelated to pyothorax, and five EBV-bearing lymphoblastic tumors produced in severe combined immune deficient mice (severe combined immune deficient-EBV+ tumors) were also studied as controls. Marked expression of EB nuclear antigen-2 was demonstrated on all four PALs. LMP-1 was also present in all cases, but both the staining intensity and the number of stained cells remained less than on severe combined immune deficient-EBV+ tumors. Neither EB nuclear antigen-2 nor LMP-1 was observed in the 50 control B-cell lymphomas. Additional molecular genetic analysis revealed that EBVs are incorporated into each PAL clonally. These results confirm the definite association of EBV with PALs, although the significance of weak expression of LMP-1 awaits further study. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8238246

  12. Department of Energy: An Organizational Look at Americas Nuclear Deterrent

    DTIC Science & Technology

    2016-09-01

    study performs a detailed literature review to identify and understand major 5 organizational cultural challenges. The literature review provides the...DEPARTMENT OF ENERGY: AN ORGANIZATIONAL LOOK AT AMERICA’S NUCLEAR DETERRENT GRADUATE RESEARCH PAPER David O. Pabst, Maj, USAF...DEPARTMENT OF ENERGY: AN ORGANIZATIONAL LOOK AT AMERICA’S NUCLEAR DETERRENT GRADUATE RESEARCH PAPER Presented to the Faculty

  13. Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

    PubMed

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2011-07-01

    Studies of nuclear workers make it possible to directly quantify the risks associated with ionizing radiation exposure at low doses and low dose rates. Studies of the CEA (Commissariat à l'Energie Atomique) and AREVA Nuclear Cycle (AREVA NC) cohort, currently the most informative such group in France, describe the long-term risk to nuclear workers associated with external exposure. Our aim is to assess the risk of mortality from solid cancers among CEA and AREVA NC nuclear workers and its association with external radiation exposure. Standardized mortality ratios (SMRs) were calculated and internal Poisson regressions were conducted, controlling for the main confounding factors [sex, attained age, calendar period, company and socioeconomic status (SES)]. During the period 1968-2004, there were 2,035 solid cancers among the 36,769 CEA-AREVA NC workers. Cumulative external radiation exposure was assessed for the period 1950-2004, and the mean cumulative dose was 12.1 mSv. Mortality rates for all causes and all solid cancers were both significantly lower in this cohort than in the general population. A significant excess of deaths from pleural cancer, not associated with cumulative external dose, was observed, probably due to past asbestos exposure. We observed a significant excess of melanoma, also unassociated with dose. Although cumulative external dose was not associated with mortality from all solid cancers, the central estimated excess relative risk (ERR) per Sv of 0.46 for solid cancer mortality was higher than the 0.26 calculated for male Hiroshima and Nagasaki A-bomb survivors 50 years or older and exposed at the age of 30 years or older. The modification of our results after stratification for SES demonstrates the importance of this characteristic in occupational studies, because it makes it possible to take class-based lifestyle differences into account, at least partly. These results show the great potential of a further joint international study of

  14. Nuclear Education Update.

    ERIC Educational Resources Information Center

    Winter, Metta L.

    1986-01-01

    Addresses the controversial issue of nuclear education in public schools. Highlights include resolutions passed by the National Congress of Parent Teacher Associations, what nuclear education is, distinction between nuclear education and education in the nuclear age, educational materials, a review of teaching materials, nuclear literacy, and…

  15. Nuclear Education Update.

    ERIC Educational Resources Information Center

    Winter, Metta L.

    1986-01-01

    Addresses the controversial issue of nuclear education in public schools. Highlights include resolutions passed by the National Congress of Parent Teacher Associations, what nuclear education is, distinction between nuclear education and education in the nuclear age, educational materials, a review of teaching materials, nuclear literacy, and…

  16. Idealism and romantic patriotism for science - an interview with José Francisco David-Ferreira.

    PubMed

    David-Ferreira, José Francisco

    2009-01-01

    Jose Francisco David-Ferreira is one of the most influential Professors of Cell and Developmental Biology in Portugal. David-Ferreira pioneered the use of electron microscopy in cell biology and experimental embryology. He also paved the way for successive generations of biologists who cross-fertilized the national scientific community. As we discuss briefly below, David-Ferreira is above all a Pedagogue and an Institution builder.

  17. Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma.

    PubMed

    van der Watt, Pauline J; Zemanay, Widaad; Govender, Dhirendra; Hendricks, Denver T; Parker, M I; Leaner, Virna D

    2014-08-01

    The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.

  18. Small nuclear ribonucleoproteins of Drosophila: Identification of U1 RNA-associated proteins and their behavior during heat shock

    SciTech Connect

    Wieben, E.D.; Pederson, T.

    1982-08-01

    In Drosophila, two nuclear proteins of approximately 26,000 and 14,000 molecular weight are recognized by a human autoimmune antibody for mammalian ribonucleoprotein (RNP) particles that contain U1 small nuclear RNA. The antibody-selected Drosophila RNP contains, in addition to these two proteins, a single RNA species that has been identified as U1 by hybridization with a cloned Drosophila U1 DNA probe. Small nuclear RNP isolated from human cells under the same conditions as used for Drosophila and selected by the anti-U1 RNP-specific antibody contains eight proteins, two of which are similar in molecular weight to the two Drosophila U1 RNP proteins. Thus, even though the nucleotide sequences of Drosophila and human U1 RNA are about 72% homologous, and the corresponding RNPs are both recognized by the same human autoantibody, Drosophila U1 RNP appears to have a simpler protein complement that its mammalian counterpart. The two Drosophila U1 RNA-associated proteins are synthesized at normal or slightly increased rates during the heat shock response and are incorporated into antibody-recognizable RNP complexes. This raises the possibility that U1 RNP is an indispensable nuclear element for cell survival during heat shock.

  19. Biological Significance of Unwinding Capability of Nuclear Matrix-Associating DNAs

    NASA Astrophysics Data System (ADS)

    Bode, J.; Kohwi, Y.; Dickinson, L.; Joh, T.; Klehr, D.; Mielke, C.; Kohwi-Shigematsu, T.

    1992-01-01

    Matrix attachment regions (MARs) are thought to separate chromatin into topologically constrained loop domains. A MAR located 5' of the human β-interferon gene becomes stably base-unpaired under superhelical strain, as do the MARs flanking the immunoglobulin heavy chain gene enhancer; in both cases a nucleation site exists for DNA unwinding. Concatemerized oligonucleotides containing the unwinding nucleation site exhibited a strong affinity for the nuclear scaffold and augmented SV40 promoter activity in stable transformants. Mutated concatemerized oligonucleotides resisted unwinding, showed weak affinity for the nuclear scaffold, and did not enhance promoter activity. These results suggest that the DNA feature capable of relieving superhelical strain is important for MAR functions.

  20. Nuclear Safety

    SciTech Connect

    Silver, E G

    1989-01-01

    This document is a review journal that covers significant developments in the field of nuclear safety. Its scope includes the analysis and control of hazards associated with nuclear energy, operations involving fissionable materials, and the products of nuclear fission and their effects on the environment. Primary emphasis is on safety in reactor design, construction, and operation; however, the safety aspects of the entire fuel cycle, including fuel fabrication, spent-fuel processing, nuclear waste disposal, handling of radioisotopes, and environmental effects of these operations, are also treated.

  1. Nuclear ubiquitin C-terminal hydrolase L5 expression associates with increased patient survival in pancreatic ductal adenocarcinoma.

    PubMed

    Arpalahti, Leena; Saukkonen, Kapo; Hagström, Jaana; Mustonen, Harri; Seppänen, Hanna; Haglund, Caj; Holmberg, Carina I

    2017-06-01

    Pancreatic ductal adenocarcinoma is a lethal disease with an overall 5-year survival of less than 5%. Prognosis among surgically treated patients is difficult and identification of new biomarkers is essential for accurate prediction of patient outcome. As part of one of the major cellular protein degradation systems, the proteasome plays a fundamental role in both physiological and pathophysiological conditions including cancer. The proteasome-associated deubiquitinating enzyme ubiquitin C-terminal hydrolase L5 (UCHL5)/Uch37 is a modulator of proteasome activity with cancer prognostic marker potential. Cytoplasmic and nuclear immunoexpression of UCHL5 was evaluated in 154 surgical specimens from pancreatic ductal adenocarcinoma patients treated at Helsinki University Hospital, Finland, in 2000-2011. UCHL5 expression in relation to clinicopathological parameters and the association between UCHL5 In this study, positive expression and patient survival were assessed. Positive nuclear UCHL5 expression was associated with increased patient survival ( p = 0.005). A survival benefit was also detectable in these subgroups of patients: over 65 years ( p < 0.001), at tumor stages IIB to III ( p = 0.007), or with lymph-node positivity ( p = 0.006). In stages IIB to III disease, patients with positive nuclear UCHL5 expression showed a twofold increase in 5-year cancer-specific survival compared to those with negative expression. Multivariate analysis identified positive nuclear UCHL5 expression as an independent prognostic factor ( p = 0.012). In conclusion, UCHL5 expression could function as a prognostic marker in pancreatic ductal adenocarcinoma, particularly at disease stages IIB to III. As UCHL5 is one of the few markers predicting increased survival, our results may be of clinical relevance.

  2. Theoretical nuclear physics. Final report

    SciTech Connect

    1997-05-01

    As the three-year period FY93-FY96 ended, there were six senior investigators on the grant full-time: Bulgac, Henley, Miller, Savage, van Kolck and Wilets. This represents an increase of two members from the previous three-year period, achieved with only a two percent increase over the budget for FY90-FY93. In addition, the permanent staff of the Institute for Nuclear Theory (George Bertsch, Wick Haxton, and David Kaplan) continued to be intimately associated with our physics research efforts. Aurel Bulgac joined the Group in September, 1993 as an assistant professor, with promotion requested by the Department and College of Arts and Sciences by September, 1997. Martin Savage, who was at Carnegie-Mellon University, jointed the Physics Department in September, 1996. U. van Kolck continued as research assistant professor, and we were supporting one postdoctoral research associate, Vesteinn Thorssen, who joined us in September, 1995. Seven graduate students were being supported by the Grant (Chuan-Tsung Chan, Michael Fosmire, William Hazelton, Jon Karakowski, Jeffrey Thompson, James Walden and Mitchell Watrous).

  3. Genome Assembly of Citrus Leprosis Virus Nuclear Type Reveals a Close Association with Orchid Fleck Virus

    PubMed Central

    Stone, Andrew; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Shao, Jonathan; Levy, Laurene; Nakhla, Mark K.; Hollingsworth, Charla R.; Hartung, John S.; Schneider, William L.

    2013-01-01

    The complete genome of citrus leprosis virus nuclear type (CiLV-N) was identified by small RNA sequencing utilizing leprosis-affected citrus samples collected from the state of Querétaro, Mexico. The nucleotide identity and phylogenetic analysis indicate that CiLV-N is very closely related to orchid fleck virus, which typically infects Cymbidium species. PMID:23887919

  4. CORROSION ISSUES ASSOCIATED WITH AUSTENITIC STAINLESS STEEL COMPONENTS USED IN NUCLEAR MATERIALS EXTRACTION AND SEPARATION PROCESSES

    SciTech Connect

    Mickalonis, J.; Louthan, M.; Sindelar, R.

    2012-12-17

    This paper illustrated the magnitude of the systems, structures and components used at the Savannah River Site for nuclear materials extraction and separation processes. Corrosion issues, including stress corrosion cracking, pitting, crevice corrosion and other corrosion induced degradation processes are discussed and corrosion mitigation strategies such as a chloride exclusion program and corrosion release testing are also discussed.

  5. SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies

    SciTech Connect

    Haekli, Marika; Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J. . E-mail: jorma.palvimo@helsinki.fi

    2005-03-10

    Small nuclear RING finger protein SNURF (RNF4) is involved in transcriptional and cell growth regulation. We show here that a significant portion of endogenous SNURF localizes to nuclear bodies (NBs) that overlap with or are adjacent to domains containing endogenous promyelocytic leukemia (PML) protein and small ubiquitin-like modifier-1 (SUMO-1). In biochemical assays, SNURF efficiently binds SUMO-1 in a noncovalent fashion. SNURF is also covalently modified by SUMO-1 at nonconsensus attachment sites. Ectopic expression of SUMO-1 markedly enhances the interaction between PML3 (PML IV) and SNURF, but covalent attachment of SUMO-1 to neither protein is required. Moreover, overexpression of PML3, but not PML-L (PML III), abolishes the coactivation function of SNURF in transactivation assays, which parallels the ability of PML3 to recruit SNURF to nuclear bodies. In sum, we have identified SNURF as a novel component in PML bodies and suggest that SUMO-1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of SNURF.

  6. Genome assembly of citrus leprosis virus nuclear type reveals a close association with orchid fleck virus.

    PubMed

    Roy, Avijit; Stone, Andrew; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Shao, Jonathan; Levy, Laurene; Nakhla, Mark K; Hollingsworth, Charla R; Hartung, John S; Schneider, William L; Brlansky, Ronald H

    2013-07-25

    The complete genome of citrus leprosis virus nuclear type (CiLV-N) was identified by small RNA sequencing utilizing leprosis-affected citrus samples collected from the state of Querétaro, Mexico. The nucleotide identity and phylogenetic analysis indicate that CiLV-N is very closely related to orchid fleck virus, which typically infects Cymbidium species.

  7. The scope for nuclear selection within Termitomyces fungi associated with fungus-growing termites is limited

    PubMed Central

    2014-01-01

    Background We investigate the scope for selection at the level of nuclei within fungal individuals (mycelia) of the mutualistic Termitomyces cultivated by fungus-growing termites. Whereas in most basidiomycete fungi the number and kind of nuclei is strictly regulated to be two per cell, in Termitomyces mycelia the number of nuclei per cell is highly variable. We hypothesised that natural selection on these fungi not only occurs between mycelia, but also at the level of nuclei within the mycelium. We test this hypothesis using in vitro tests with five nuclear haplotypes of a Termitomyces species. Results First, we studied the transition from a mixture of five homokaryons (mycelia with identical nuclei) each with a different nuclear haplotype to heterokaryons (mycelia with genetically different nuclei). In vitro cultivation of this mixture for multiple asexual transfers led to the formation of multiple heterokaryotic mycelia, and a reduction of mycelial diversity over time. All heterokaryotic mycelia contained exactly two types of nucleus. The success of a heterokaryon during in vitro cultivation was mainly determined by spore production and to a lesser extent by mycelial growth rate. Second, heterokaryons invariably produced more spores than homokaryons implying that homokaryons will be outcompeted. Third, no homokaryotic ‘escapes’ from a heterokaryon via the formation of homokaryotic spores were found, despite extensive spore genotyping. Fourth, in contrast to most studied basidiomycete fungi, in Termitomyces sp. no nuclear migration occurs during mating, limiting the scope for nuclear competition within the mycelium. Conclusions Our experiments demonstrate that in this species of Termitomyces the scope for selection at the level of the nucleus within an established mycelium is limited. Although ‘mate choice’ of a particular nuclear haplotype is possible during mating, we infer that selection primarily occurs between mycelia with two types of nucleus

  8. Cdc48 and Ubx1 participate in a pathway associated with the inner nuclear membrane that governs Asi1 degradation.

    PubMed

    Pantazopoulou, Marina; Boban, Mirta; Foisner, Roland; Ljungdahl, Per O

    2016-10-15

    The nuclear envelope is a barrier comprising outer and inner membranes that separate the cytoplasm from the nucleoplasm. The two membranes have different physical characteristics and protein compositions. The processes governing the stability of inner nuclear membrane (INM) proteins are not well characterized. In Saccharomyces cerevisiae, the INM Asi1-Asi3 complex, principally composed of integral membrane proteins Asi1 and Asi3, is an E3 ubiquitin ligase. In addition to its well-documented function in endoplasmic reticulum (ER)-associated degradation, the Doa10 E3 ubiquitin ligase complex partially localizes to the INM. The Asi1-Asi3 and Doa10 complexes define independent INM-associated degradation (INMAD) pathways that target discrete sets of nuclear substrates for proteasomal degradation. Here, we report that Asi1 is rapidly turned over (t1/2≤30 min). Its turnover depends on ubiquitin-mediated degradation by nucleus-localized proteasomes, exhibiting a clear requirement for the E2 ubiquitin-conjugating enzyme Ubc7, Cue1 and the AAA ATPase Cdc48 and co-factor Ubx1. Asi1 turnover occurs largely independently of the Asi1-Asi3 or Doa10 complexes, indicating that it is subject to quality control at the INM in a manner distinct from that of the characterized INMAD pathways. © 2016. Published by The Company of Biologists Ltd.

  9. Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi's Sarcoma-Associated Herpesvirus for Viral Latency.

    PubMed

    Wang, Chong; Zhu, Caixia; Wei, Fang; Gao, Shujun; Zhang, Liming; Li, Yuhong; Feng, Yanling; Tong, Yin; Xu, Jianqing; Wang, Bin; Yuan, Zhenghong; Robertson, Erle S; Cai, Qiliang

    2017-01-01

    Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonstrated that KSHV blocks IL-4-induced STAT6 phosphorylation and retains a basal IL-13/STAT6 constitutive activation for cell survival and proliferation. However, the mechanism by which KSHV regulates STAT6 remains largely unknown. Here, we found that KSHV-encoded LANA interacts with STAT6 and promotes nuclear localization of STAT6 independent of the tyrosine 641-phosphorylation state. Moreover, nuclear localization of STAT6 is also dramatically increased in KS tissue. The latent antigen LANA induces serine protease-mediated cleavage of STAT6 in the nucleus, where the cleaved STAT6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of Replication and Transcription Activator (RTA) and in turn shut off viral lytic replication. Blockade of STAT6 by small interference RNA dramatically enhances expression of RTA, and in turn reduces KSHV-infected endothelial cell growth and colony formation. Taken together, these results suggest that nuclear localization and cleavage of STAT6 is important for modulating the viral latency and pathogenesis of KSHV.

  10. Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi’s Sarcoma-Associated Herpesvirus for Viral Latency

    PubMed Central

    Zhang, Liming; Li, Yuhong; Feng, Yanling; Xu, Jianqing; Wang, Bin; Yuan, Zhenghong; Robertson, Erle S.; Cai, Qiliang

    2017-01-01

    Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi’s sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonstrated that KSHV blocks IL-4-induced STAT6 phosphorylation and retains a basal IL-13/STAT6 constitutive activation for cell survival and proliferation. However, the mechanism by which KSHV regulates STAT6 remains largely unknown. Here, we found that KSHV-encoded LANA interacts with STAT6 and promotes nuclear localization of STAT6 independent of the tyrosine 641-phosphorylation state. Moreover, nuclear localization of STAT6 is also dramatically increased in KS tissue. The latent antigen LANA induces serine protease-mediated cleavage of STAT6 in the nucleus, where the cleaved STAT6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of Replication and Transcription Activator (RTA) and in turn shut off viral lytic replication. Blockade of STAT6 by small interference RNA dramatically enhances expression of RTA, and in turn reduces KSHV-infected endothelial cell growth and colony formation. Taken together, these results suggest that nuclear localization and cleavage of STAT6 is important for modulating the viral latency and pathogenesis of KSHV. PMID:28099521

  11. Increased receptor for advanced glycation end products in spermatozoa of diabetic men and its association with sperm nuclear DNA fragmentation.

    PubMed

    Karimi, J; Goodarzi, M T; Tavilani, H; Khodadadi, I; Amiri, I

    2012-05-01

    Although the majority of patients with diabetes have disorders in sexual function, associations between diabetes mellitus and sperm function at the molecular level are largely unknown. As receptor for advanced glycation end products plays a key role in many diabetic complications, we hypothesised that it may be involved in sperm nuclear DNA fragmentation. RAGE levels were determined using ELISA and western blot analysis in sperm samples from 32 diabetic and 35 nondiabetic men. Sperm DNA fragmentation was assessed using TUNEL assay. Diabetic men had significantly higher mean levels of RAGE protein (P < 0.001) and DNA fragmentation (P < 0.001) in spermatozoa. Sperm RAGE was directly correlated to sperm DNA fragmentation in diabetic men (r = 0.81, P < 0.001). The high positive correlation between RAGE levels and nuclear DNA fragmentation in spermatozoa of diabetic men suggests a central role of RAGE in disturbances in sexual function of diabetic men. © 2011 Blackwell Verlag GmbH.

  12. Inductively Coupled Plasma/Mass Spectrometric Isotopic Determination of Nuclear Wastes Sources Associated with Hanford Tank Leaks

    SciTech Connect

    Evans, John C.; Dresel, P. Evan; Farmer, Orville T.

    2007-11-01

    The subsurface distribution of a nuclear waste tank leak on the U.S. Department of Energy’s Hanford Site was sampled by slant drilling techniques in order to characterize the chemical and radiological characteristics of the leaked material and assess geochemical transport properties of hazardous constituents. Sediment core samples recovered from the borehole were subjected to distilled water and acid leaching procedures with the resulting leachates analyzed for isotopic and chemical signatures. High-sensitivity inductively coupled plasma/mass spectrometry (ICP/MS) techniques were used for determination of isotopic ratios for Cs, I, Mo. Analysis of the isotopic patterns of I and Mo combined with associated chemical data showed evidence for at least two separate intrusions of nuclear waste into the subsurface. Isotopic data for Cs was inconclusive with respect to a source attribution signature.

  13. Electron Distributions in Hexagonal Selenium and Tellurium and Monoclinic Selenium with Dilute Impurities and Associated Nuclear Quadrupole Interactions*.

    NASA Astrophysics Data System (ADS)

    Maharjan, N. B.; Paudyal, D. D.; Mishra, D. R.; Byahut, S.; Aryal, M. M.; Cho, Hwa-Suck; Scheicher, R. H.; Chow, Lee; Jeong, Junho; Das, T. P.

    2006-03-01

    The electron structures of Selenium chains and rings with Te impurities in hexagonal and monoclinic structures respectively and Se impurities in Te chains in hexagonal lattice have been studied using Hartree-Fock cluster model including many-body effects, including lattice relaxation effects. The calculated electronic wave-functions are utilized to obtain ^77Se and ^125Te nuclear quadrupole coupling constants e^2qQ and asymmetry parameters η and compared with available experimental data from Mossbauer and perturbed angular correlation measurements. From our results, the expected nature of nuclear quadrupole interactions associated with Sb impurities will be discussed. *Supported by NSF US-Nepal Program and UGC Nepal **Also at UCF, Orlando

  14. Novel Problems Associated with Accounting and Control of Nuclear Material from Decontamination and Decommissioning and in Waste

    SciTech Connect

    Schlegel, Steven C.

    2007-01-10

    The United States is eliminating many facilities that support the nuclear weapons program. With the changing political conditions around the world and changes in military capabilities, the decreased emphasis on nuclear weapons has eliminated the need for many of the aging facilities. Since weapons program and commercial applications do not mix in the United States, the facilities in the weapons complex that no longer have a mission are being deinventoried, decontaminated, decommissioned, and dismantled/demolished. The materials from these activities are then disposed of in various ways but usually in select waste burial sites. Additionally, the waste in many historical burial sites associated with the weapons complex are being recovered, repackaged if necessary, and disposed of in either geological sites or low-level waste sites.

  15. David Hartley's views on Madness: With an introduction by GE Berrios.

    PubMed

    Berrios, G E

    2015-03-01

    The psychiatric aspects of David Hartley's writings have received less attention than the rest of his work. This Classic Text deals with Section VI of his Observations on Man …, namely, the 'Imperfections of the rational Faculty'. Hartley defines madness as an imperfection of reason that can be temporary or enduring. He makes use of his model of mental functioning to differentiate between eight clinical categories of madness, each representing a different pattern of vibrations of the nerves. Hartley developed this model based on Newton's theory of vibrations and, to explain the complexity of mental acts and entities, he combined it with his own version of the mechanism of Association of Ideas borrowed from John Locke. Much work needs to be done to identify the provenance of Hartley's nosology and nosography.

  16. Glucocorticoid modulation of androgen receptor nuclear aggregation and cellular toxicity is associated with distinct forms of soluble expanded polyglutamine protein.

    PubMed

    Welch, W J; Diamond, M I

    2001-12-15

    Spinobulbar muscular atrophy is a progressive motor neuron disease caused by abnormal polyglutamine tract expansion in the androgen receptor (AR) gene, and is part of a family of central nervous system (CNS) neurodegenerative diseases, including Huntington's disease (HD). Each pathologic protein is widely expressed, but the cause of neuronal degeneration within the CNS remains unknown. Many reports now link abnormal polyglutamine protein aggregation to pathogenesis. A previous study reported that activation of the wild-type glucocorticoid receptor (wtGR) suppressed the aggregation of expanded polyglutamine proteins derived from AR and huntingtin, whereas a mutant receptor containing an internal deletion, GRDelta108-317, increased polyglutamine protein aggregation, in this case primarily within the nucleus. In this study, we use these two forms of GR to study expanded polyglutamine AR protein in different cell contexts. Using cell biology and biochemical approaches, we find that wtGR promotes soluble forms of the protein and prevents nuclear aggregation in NIH3T3 cells and cultured neurons. In contrast, GRDelta108-317 decreases polyglutamine protein solubility, and causes formation of nuclear aggregates in non-neuronal cells. Nuclear aggregates recruit hsp72 more rapidly than cytoplasmic aggregates, and are associated with decreased cell viability. Limited proteolysis and chemical cross-linking suggest unique soluble forms of the expanded AR protein underlie these distinct biological activities. These observations provide an experimental framework to understand why expanded polyglutamine proteins may be toxic only to certain populations of cells, and suggest that unique protein associations or conformations of expanded polyglutamine proteins may determine subsequent cellular effects such as nuclear localization and cellular toxicity.

  17. David Duke, running for governor, proposes tattooing people with HIV.

    PubMed

    1995-05-19

    Former Ku Klux Klan leader, David Duke, planning a second run for governor of Louisiana, said he would curb the AIDS epidemic by tattooing people who are infected with HIV. His suggestion is to put indelible, glow-in-the-dark tattoos on the genitals of people infected with HIV. According to Duke, it may sound very draconian but it would not demean people. He also believes that tattooing would be legal because courts have a history of supporting the quarantining and institutionalizing of people with infectious diseases, such as tuberculosis. Duke said Cuba has had some success in using quarantines to reduce HIV infection, but he does not think it would work in the United States because it would cost too much. According to Duke, many people who get HIV from irresponsible behavior do not tell their partners that they have AIDS--these people are mad at the world and engage in dangerous behaviors even more.

  18. STS-107 Crew Interviews: David Brown MS1

    NASA Technical Reports Server (NTRS)

    2002-01-01

    STS-107 Mission Specialist 1 David Brown is seen during this preflight interview where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his career. Brown outlines his role in the mission in general, and specifically during the conducting of on-board science experiments. Brown discusses the following instruments and experiments in detail: ARMS (Advanced Respiratory Monitoring System), MEIDEX (Mediterranean Israeli Dust Experiment), Combustion Module 2, and FREESTAR (Fast Reaction Enables Science Technology and Research). He also describes the new primary payload carrier, the SPACEHAB research double module which doubles the amount of space available for research. Brown shares his thoughts about the importance of international cooperation in mission planning and the need for scientific research in space.

  19. Astronaut David Brown talks with team members from South Carolina

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown looks over the robot named 'L'il Max' with members of the team The Bot Kickers! from Northwestern High School, Rock Hill, S.C. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition being held March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co- sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  20. Astronaut David Brown poses with ComBBat team

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown poses with members of the team known as ComBBat, representing Central Florida's Astronaut and Titusville high schools. ComBBat was teamed with Boeing at KSC and Brevard Community College. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition being held March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  1. Astronaut David Brown talks to FIRST team members

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown talks with FIRST team members, Baxter Bomb Squad, from Mountain Home High School, Mountain Home, Ariz., during the FIRST competition. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  2. Storm-surge measurements and computations for Hurricane David

    SciTech Connect

    Howell, G.; Lee, D.Y.; Wang, H.

    1982-08-01

    One of the objectives of the Coastal Data Network System established and maintained by the Coastal and Oceanographic Engineering Laboratory at the University of Florida is to acquire and document storm surge data along the Florida Coast. Since the establishment of the system only one major hurricane resulted in storm surge of significance. This was Hurricane David which swept through the lower part of Florida's east coast in September 1979. Storm surge data were obtained at Miami Beach, Palm Beach, and Vero Beach. These data were analyzed and documented. In addition, the numerical storm surge model developed by Dean and Chiu was used to compute the storm surges at Palm Beach and Vero Beach to facilitate comparisons.

  3. STS-107 Crew Interviews: David Brown MS1

    NASA Technical Reports Server (NTRS)

    2002-01-01

    STS-107 Mission Specialist 1 David Brown is seen during this preflight interview where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his career. Brown outlines his role in the mission in general, and specifically during the conducting of on-board science experiments. Brown discusses the following instruments and experiments in detail: ARMS (Advanced Respiratory Monitoring System), MEIDEX (Mediterranean Israeli Dust Experiment), Combustion Module 2, and FREESTAR (Fast Reaction Enables Science Technology and Research). He also describes the new primary payload carrier, the SPACEHAB research double module which doubles the amount of space available for research. Brown shares his thoughts about the importance of international cooperation in mission planning and the need for scientific research in space.

  4. STS-86 Mission Specialist David Wolf suits up

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-86 Mission Specialist David A. Wolf gets assistance from a suit technician while donning his orange launch and entry suit in the Operations and Checkout Building. This will be Wolfs second flight. He and the six other crew members will depart shortly for Launch Pad 39A, where the Space Shuttle Atlantis awaits liftoff on a 10-day mission slated to be the seventh docking of the Space Shuttle with the Russian Space Station Mir. Wolf will transfer to the Mir 24 crew, replacing U.S. astronaut C. Michael Foale, who will return to Earth aboard Atlantis with the rest of the STS-86 crew. Wolf is expected to live and work aboard the Russian space station for about four months.

  5. Astronaut David Brown talks with team members from South Carolina

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown looks over the robot named 'L'il Max' with members of the team The Bot Kickers! from Northwestern High School, Rock Hill, S.C. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition being held March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co- sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  6. Astronaut David Brown talks to FIRST team members

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown talks with FIRST team members, Baxter Bomb Squad, from Mountain Home High School, Mountain Home, Ariz., during the FIRST competition. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  7. Astronaut David Brown poses with ComBBat team

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown poses with members of the team known as ComBBat, representing Central Florida's Astronaut and Titusville high schools. ComBBat was teamed with Boeing at KSC and Brevard Community College. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition being held March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  8. The challenges and future of oral drug delivery: An interview with David Brayden.

    PubMed

    Brayden, David J

    2016-12-01

    David Brayden speaks to Hannah Makin, Commissioning Editor: David Brayden is a Full Professor (Advanced Drug Delivery) at the School of Veterinary Medicine, University College Dublin (UCD) and also a Fellow of the UCD Conway Institute. Following a PhD in Pharmacology at the University of Cambridge, UK (1989), and a postdoctoral research fellowship at Stanford University, CA, USA, he set up Elan Biotechnology Research's in vitro pharmacology laboratory in Dublin (1991). At Elan, he became a senior scientist and project manager of several of Elan's joint-venture drug delivery research collaborations with US biotech companies. In 2001, he joined UCD as a lecturer in veterinary pharmacology and was appointed Associate Professor in 2006 and Full Professor in 2014. He was a Director of the Science Foundation Ireland Research Cluster (The Irish Drug Delivery Research Network) from 2007 to 2013, is a Deputy Coordinator of an FP7 Consortium on oral peptides in nanoparticles ('TRANS-INT', 2012-2017), and is a Co-Principal Investigator in 'CURAM', Science Foundation Ireland's new Centre for Medical Devices (2014-2020 [ 1 ]). He was made a Fellow of the Controlled Release Society in 2012. He is the author or co-author of >200 research publications and patents. D Brayden serves on the Editorial Advisory Boards of Drug Discovery Today, European Journal of Pharmaceutical Sciences, Advanced Drug Delivery Reviews and the Journal of Veterinary Pharmacology and Therapeutics, and is an Associate Editor of Therapeutic Delivery. D Brayden works as an independent consultant for drug delivery companies.

  9. Nuclear alterations associated to programmed cell death in larval salivary glands of Apis mellifera (Hymenoptera: Apidae).

    PubMed

    Silva-Zacarin, E C M; Taboga, S R; Silva de Moraes, R L M

    2008-01-01

    The silk glands of bees are a good model for the study of cell death in insects. With the objective to detect the nuclear features during glandular regression stage, larvae at the last instar and pre-pupae were collected and their silk glands were dissected and processed for ultrastructural analysis and histologically for cytochemical and imunocytochemical analysis. The results showed that the cellular nuclei exhibited characteristics of death by atypical apoptosis as well as autophagic cell death. Among the apoptosis characteristic were: nuclear strangulation with bleb formation in some nuclei, DNA fragmentation in most of the nuclei and nucleolar fragmentation. Centripetal chromatin compaction was observed in many nuclei, forming a perichromatin halo differing from typical apoptotic nuclei. With regards to the characteristics of autophagic-programmed cell death, most relevant was the delay in the collapse of many nuclei.

  10. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

    PubMed Central

    Olivares, Ana Maria; Moreno-Ramos, Oscar Andrés; Haider, Neena B.

    2015-01-01

    The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration. PMID:27168725

  11. Nuclear import of RNA polymerase II is coupled with nucleocytoplasmic shuttling of the RNA polymerase II-associated protein 2.

    PubMed

    Forget, Diane; Lacombe, Andrée-Anne; Cloutier, Philippe; Lavallée-Adam, Mathieu; Blanchette, Mathieu; Coulombe, Benoit

    2013-08-01

    The RNA polymerase II (RNAP II)-associated protein (RPAP) 2 has been discovered through its association with various subunits of RNAP II in affinity purification coupled with mass spectrometry experiments. Here, we show that RPAP2 is a mainly cytoplasmic protein that shuttles between the cytoplasm and the nucleus. RPAP2 shuttling is tightly coupled with nuclear import of RNAP II, as RPAP2 silencing provokes abnormal accumulation of RNAP II in the cytoplasmic space. Most notably, RPAP4/GPN1 silencing provokes the retention of RPAP2 in the nucleus. Our results support a model in which RPAP2 enters the nucleus in association with RNAP II and returns to the cytoplasm in association with the GTPase GPN1/RPAP4. Although binding of RNAP II to RPAP2 is mediated by an N-terminal domain (amino acids 1-170) that contains a nuclear retention domain, and binding of RPAP4/GPN1 to RPAP2 occurs through a C-terminal domain (amino acids 156-612) that has a dominant cytoplasmic localization domain. In conjunction with previously published data, our results have important implications, as they indicate that RPAP2 controls gene expression by two distinct mechanisms, one that targets RNAP II activity during transcription and the other that controls availability of RNAP II in the nucleus.

  12. Distribution of nuclear mitochondrial pseudogenes in three pollinator fig wasps associated with Ficus pumila

    NASA Astrophysics Data System (ADS)

    Chen, Yan; Liu, Min; Compton, Stephen G.; Chen, Xiao-Yong

    2014-05-01

    Nuclear mitochondrial pseudogenes (NUMTs) are nuclear sequences transferred from mitochondrial genomes. Although widespread, their distribution patterns among populations or closely related species are rarely documented. We amplified and sequenced the mitochondrial cytochrome b (Cytb) gene to check for NUMTs in three fig wasp species that pollinate Ficus pumila (Wiebesia sp. 1, 2 and 3) in Southeastern China using direct and cloned sequencing. Unambiguous sequences (332) of 487 bp in length belonging to 33 haplotypes were found by direct sequencing. Their distribution was highly concordant with those of cytochrome c oxidase subunit I (COI). Obvious signs of co-amplification of NUMTs were indicated by their uneven distribution. NUMTs were observed in all individuals of 12 populations of Wiebesia sp. 3, and 13 individuals of three northern populations of Wiebesia sp. 1. Sequencing clones of potential co-amplification products confirmed that they were NUMTs. These NUMTs either clustered as NUMT clades basal to mtDNA Cytb clades (basal NUMTs), or together with Cytb haplotypes. Basal NUMTs had either stop codons or frame-shifting mutations resulting from deletion of a 106 bp fragment. In addition, no third codon or synonymous substitutions were detected within each NUMT clade. The phylogenetic tree indicated that basal NUMTs had been inserted into nuclei before divergence of the three species. No significant pairwise differences were detected in their ratios of third codon substitutions, suggesting that these NUMTs originated from one transfer event, with duplication in the nuclear genome resulting in the coexistence of the 381 bp copy. No significant substitution differences were detected between Cytb haplotypes and NUMTs that clustered with Cytb haplotypes. However, these NUMTs coexisted with Cytb haplotypes in multiple populations, suggesting that these NUMT haplotypes were recently inserted into the nuclear genome. Both basal and recently inserted NUMTs were rare

  13. From Ground Truth to Space: Surface, Subsurface and Remote Observations Associated with Nuclear Test Detection

    NASA Astrophysics Data System (ADS)

    Sussman, A. J.; Anderson, D.; Burt, C.; Craven, J.; Kimblin, C.; McKenna, I.; Schultz-Fellenz, E. S.; Miller, E.; Yocky, D. A.; Haas, D.

    2016-12-01

    Underground nuclear explosions (UNEs) result in numerous signatures that manifest on a wide range of temporal and spatial scales. Currently, prompt signals, such as the detection of seismic waves provide only generalized locations and the timing and amplitude of non-prompt signals are difficult to predict. As such, research into improving the detection, location, and identification of suspect events has been conducted, resulting in advancement of nuclear test detection science. In this presentation, we demonstrate the scalar variably of surface and subsurface observables, briefly discuss current capabilities to locate, detect and characterize potential nuclear explosion locations, and explain how emergent technologies and amalgamation of disparate data sets will facilitate improved monitoring and verification. At the smaller scales, material and fracture characterization efforts on rock collected from legacy UNE sites and from underground experiments using chemical explosions can be incorporated into predictive modeling efforts. Spatial analyses of digital elevation models and orthoimagery of both modern conventional and legacy nuclear sites show subtle surface topographic changes and damage at nearby outcrops. Additionally, at sites where such technology cannot penetrate vegetative cover, it is possible to use the vegetation itself as both a companion signature reflecting geologic conditions and showing subsurface impacts to water, nutrients, and chemicals. Aerial systems based on RGB imagery, light detection and ranging, and hyperspectral imaging can allow for combined remote sensing modalities to perform pattern recognition and classification tasks. Finally, more remote systems such as satellite based synthetic aperture radar and satellite imagery are other techniques in development for UNE site detection, location and characterization.

  14. Behavioral differences of irradiated persons associated with the Kyshtym, Chelyabinsk, and Chernobyl nuclear accidents.

    PubMed

    Collins, D L

    1992-10-01

    Three nuclear accidents besides Chernobyl have occurred in the former Soviet Union. The accidents occurred around Kyshtym and Chelyabinsk in the Ural Mountains between 1949 and 1967 and contaminated over one-half million people. The health ministries are now interested in the data previously collected on these irradiated populations in order to examine the health (e.g., psychological, hereditary, genome damage, etc.) implications of long-term radiation exposure.

  15. Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence

    PubMed Central

    Jin, Jing; Jung, Hae Yoen; Lee, Kyu Ho; Yi, Nam-Joon; Suh, Kyung-Suk; Jang, Ja-June; Lee, Kyoung-Bun

    2016-01-01

    Background: Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients. Methods: HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining. Results: The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015). Conclusions: Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs. PMID:27086597

  16. Dss1 associating with the proteasome functions in selective nuclear mRNA export in yeast

    SciTech Connect

    Mannen, Taro; Andoh, Tomoko; Tani, Tokio

    2008-01-25

    Dss1p is an evolutionarily conserved small protein that interacts with BRCA2, a tumor suppressor protein, in humans. The Schizosaccharomyces pombe strain lacking the dss1{sup +} gene ({delta}dss1) shows a temperature-sensitive growth defect and accumulation of bulk poly(A){sup +} RNA in the nucleus at a nonpermissive temperature. In situ hybridization using probes for several specific mRNAs, however, revealed that the analyzed mRNAs were exported normally to the cytoplasm in {delta}dss1, suggesting that Dss1p is required for export of some subsets of mRNAs. We identified the pad1{sup +} gene, which encodes a component of the 26S proteasome, as a suppressor for the ts{sup -} phenotype of {delta}dss1. Unexpectedly, overexpression of Pad1p could suppress neither the defect in nuclear mRNA export nor a defect in proteasome function. In addition, loss of proteasome functions does not cause defective nuclear mRNA export. Dss1p seems to be a multifunctional protein involved in nuclear export of specific sets of mRNAs and the ubiquitin-proteasome pathway in fission yeast.

  17. Molecular anatomy of tunicate senescence: reversible function of mitochondrial and nuclear genes associated with budding cycles.

    PubMed

    Kawamura, Kaz; Kitamura, Seigo; Sekida, Satoko; Tsuda, Masayuki; Sunanaga, Takeshi

    2012-11-01

    Zooids of the asexual strain of Polyandrocarpa misakiensis have a lifespan of 4-5 months; before dying, they produce many buds, enabling continuation of the strain. This study was designed to investigate the nature of gene inactivation and reactivation during this continuous process of senescence and budding. During senescence, the zooidal epidermis showed acid β-galactosidase activity, lost proliferating cell nuclear antigen immunoreactivity and became ultrastructurally worn, indicating that the epidermis is a major tissue affected by the ageing process. Semi-quantitative PCR analysis showed that the genes encoding mitochondrial respiratory chains (MRCs) engaged in decreased transcriptional activity in senescent adults compared with younger adults. The results of in situ hybridization showed that the epidermis dramatically attenuates MRC expression during ageing but restores gene activity when budding commences. During budding and ageing, the nuclear gene Eed (a polycomb group component) was activated and inactivated in a pattern similar to that observed in MRCs. In buds, RNA interference (RNAi) of Eed attenuated Eed transcripts but did not affect the gene expression of pre-activated MRCs. A tunicate humoral factor, TC14-3, could induce Eed, accompanying the reactivation of MRC in adult zooids. When RNAi of Eed and Eed induction were performed simultaneously, zooidal cells and tissues failed to engage in MRC reactivation, indicating the involvement of Eed in MRC activation. Results of this study provide evidence that the mitochondrial gene activities of Polyandrocarpa can be reversed during senescence and budding, suggesting that they are regulated by nuclear polycomb group genes.

  18. High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer.

    PubMed

    Santagata, Sandro; Hu, Rong; Lin, Nancy U; Mendillo, Marc L; Collins, Laura C; Hankinson, Susan E; Schnitt, Stuart J; Whitesell, Luke; Tamimi, Rulla M; Lindquist, Susan; Ince, Tan A

    2011-11-08

    Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to heat and a wide variety of other stressors. We previously reported that HSF1 promotes the survival and proliferation of malignant cells. At this time, however, the clinical and prognostic significance of HSF1 in cancer is unknown. To address this issue breast cancer samples from 1,841 participants in the Nurses' Health Study were scored for levels of nuclear HSF1. Associations of HSF1 status with clinical parameters and survival outcomes were investigated by Kaplan-Meier analysis and Cox proportional hazard models. The associations were further delineated by Kaplan-Meier analysis using publicly available mRNA expression data. Our results show that nuclear HSF1 levels were elevated in ∼80% of in situ and invasive breast carcinomas. In invasive carcinomas, HSF1 expression was associated with high histologic grade, larger tumor size, and nodal involvement at diagnosis (P < 0.0001). By using multivariate analysis to account for the effects of covariates, high HSF1 levels were found to be independently associated with increased mortality (hazards ratio: 1.62; 95% confidence interval: 1.21-2.17; P < 0.0013). This association was seen in the estrogen receptor (ER)-positive population (hazards ratio: 2.10; 95% confidence interval: 1.45-3.03; P < 0.0001). In public expression profiling data, high HSF1 mRNA levels were also associated with an increase in ER-positive breast cancer-specific mortality. We conclude that increased HSF1 is associated with reduced breast cancer survival. The findings indicate that HSF1 should be evaluated prospectively as an independent prognostic indicator in ER-positive breast cancer. HSF1 may ultimately be a useful therapeutic target in cancer.

  19. 77 FR 67725 - Culturally Significant Object Imported for Exhibition Determinations: “Michelangelo's David Apollo”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Culturally Significant Object Imported for Exhibition Determinations: ``Michelangelo's David Apollo'' SUMMARY... object to be included in the exhibition ``Michelangelo's David Apollo,'' imported from abroad for... display of the exhibit object at the National Gallery of Art, Washington, DC, from on or about December...

  20. 78 FR 38363 - David A. Ruben, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration David A. Ruben, M.D.; Decision and Order On February 7, 2011, the Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement Administration, issued an Order to Show Cause to David A. Ruben, M.D. ...

  1. Building Consensus toward a Shared Purpose: A Profile of President David Gray

    ERIC Educational Resources Information Center

    Dessoff, Alan

    2011-01-01

    The author presents a profile of APPA president David Gray. One might say that David Gray's path into higher education facilities management was anything but traditional. Today, Gray is the assistant vice president of facilities services at Middle Tennessee State University. His professional career, however, actually began in banking. In 1993 he…

  2. A Cabinet of Mathematical Curiosities at Teachers College: David Eugene Smith's Collection

    ERIC Educational Resources Information Center

    Murray, Diane R.

    2012-01-01

    This dissertation is a history of David Eugene Smith's collection of historical books, manuscripts, portraits, and instruments related to mathematics. The study analyzes surviving documents, images, objects, college announcements and catalogs, and secondary sources related to Smith's collection. David Eugene Smith (1860-1944) travelled…

  3. A Cabinet of Mathematical Curiosities at Teachers College: David Eugene Smith's Collection

    ERIC Educational Resources Information Center

    Murray, Diane R.

    2012-01-01

    This dissertation is a history of David Eugene Smith's collection of historical books, manuscripts, portraits, and instruments related to mathematics. The study analyzes surviving documents, images, objects, college announcements and catalogs, and secondary sources related to Smith's collection. David Eugene Smith (1860-1944) travelled…

  4. Characterization of the bipartite nuclear localization signal of protein LANA2 from Kaposi's sarcoma-associated herpesvirus.

    PubMed Central

    Muñoz-Fontela, Cesar; Rodríguez, Estefanía; Nombela, Cesar; Arroyo, Javier; Rivas, Carmen

    2003-01-01

    LANA2 is a nuclear latent protein detected exclusively in Kaposi's sarcoma-associated herpesvirus-infected B cells. The protein inhibits p53-dependent transactivation and apoptosis, suggesting an important role in the transforming activity of the virus. To explore the molecular mechanisms of its nuclear localization, fusion proteins of green fluorescent protein (EGFP) and deletion constructs of LANA2 were expressed in HeLa cells. Only the fragment comprising amino acid residues 355-440 of LANA2 localized in the cell nucleus. This fragment contains two closely located basic domains and forms a putative bipartite nuclear localization signal (NLS). The putative LANA2 NLS was able to target EGFP to the nucleus consistently. Site-directed mutation analyses demonstrated that LANA2 contains a functional bipartite NLS between amino acid positions 367 and 384. In addition, analysis of cells transfected with a cytoplasmic LANA2 mutant revealed that an appropriate subcellular localization may be crucial to regulate p53 activity. PMID:12767255

  5. Highlights of the Annual Congress of the European Association of Nuclear Medicine, Helsinki 2004, and a dash of horizon scanning.

    PubMed

    Ell, Peter J

    2005-01-01

    The Annual Congress of the European Association of Nuclear Medicine represents the major scientific and professional event in the field of nuclear medicine in Europe. Specialists from all allied professions meet to discuss the latest findings and discoveries. A very large industrial exhibition demonstrates the latest technological innovations and developments. This Highlights Lecture summarises the scientific and medical advances discussed at this important gathering. The lecture covers a significant proportion of the data presented and/or discussed in up-to-date reviews, and places some of the trends encountered in the context of the evolution of the field as a whole. There is much food for thought in most areas of nuclear medicine: advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in known areas of clinical application such as neurology and psychiatry, cardiology, oncology, endocrine disorders, paediatrics, nephro-urology and musculoskeletal disorders. This Highlights Lecture is, however, only a brief resume of the vast amount of data discussed, which can be found in much greater detail in the Congress Proceedings, published as volume 31, supplement 2 of Eur J Nucl Med Mol Imaging in August 2004.

  6. Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

    PubMed Central

    Neems, Daniel S.; Garza-Gongora, Arturo G.; Smith, Erica D.; Kosak, Steven T.

    2016-01-01

    The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineage-enriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation. PMID:26957603

  7. HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens.

    PubMed Central

    Smolen, J S; Klippel, J H; Penner, E; Reichlin, M; Steinberg, A D; Chused, T M; Scherak, O; Graninger, W; Hartter, E; Zielinski, C C

    1987-01-01

    HLA-DR antigens and autoantibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm, and RNP were determined in North American and Austrian patients with systemic lupus erythematosus (SLE). Analysis of the association of antibodies to these ribonucleic acid (RNA)-protein antigens with HLA-DR antigens showed that HLA-DR3 was related to the presence of anti-Ro/SSA or anti-La/SSB, or both. In contrast, anti-Sm or anti-RNP, or both were associated with HLA-DR4. HLA-DR5 was associated with absence of these autoantibodies. The data extend evidence for the complexity and heterogeneity of SLE. Moreover, they indicate that, in SLE, genes linked to those coding for HLA-DR antigens, are related to the specificity of autoantibody responses rather than to the primary immunological abnormalities of this disorder. PMID:3498447

  8. Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-kappaB.

    PubMed Central

    Maschera, B; Ray, K; Burns, K; Volpe, F

    1999-01-01

    Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp340 replaced by an asparagine residue (IRAK-Asp340Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-Asp340Asn caused activation of nuclear factor kappaB, suggesting that the kinase activity of IRAK is not required outside of the IL-1R complex. PMID:10191251

  9. TSH stimulates 32P-labeling of thyroid nuclear HMG 14, a protein associated with actively transcribed chromatin

    SciTech Connect

    Cooper, E.; Palmer, R.J.; Spaulding, S.W.

    1982-04-01

    Thyroid slices were incubated with 32P with or without TSH. 32P-labeling of acid-soluble nuclear proteins was then examined by two-dimensional polyacrylamide gel electrophoresis and autoradiography. We found that TSH enhanced the labeling of the high mobility group protein HMG 14, a protein that is preferentially associated with actively transcribed chromatin. This observation suggests that changes in HMG 14 phosphorylation may be involved in mediating TSH-induced effects on the structure and function of active chromatin.

  10. Nuclear localization of heme oxygenase-1 is associated with tumor progression of head and neck squamous cell carcinomas.

    PubMed

    Gandini, Norberto A; Fermento, María E; Salomón, Débora G; Blasco, Jorge; Patel, Vyomesh; Gutkind, J Silvio; Molinolo, Alfredo A; Facchinetti, María M; Curino, Alejandro C

    2012-10-01

    The expression of heme oxygenase-1 (HO-1) was shown to be increased in multiple tumors compared with their surrounding healthy tissues and was also observed to be up-regulated in oral squamous cell carcinomas (OSCC). However, conflicting results were obtained and little information is available regarding HO-1 significance in head and neck squamous cell carcinoma (HNSCC). Therefore, the aim of the present study was to perform a wide screening of HO-1 expression in a large collection of human primary HNSCCs and to correlate the results with clinical and pathological parameters. For this purpose, we investigated the expression of this protein by immunohistochemistry (IHC) in tissue microarrays (TMAs) of HNSCC and in an independent cohort of paraffin-embedded tumor specimens. HO-1 expression was further validated by real-time qPCR performed on selected laser capture-microdissected (LCM) oral tissue samples. Both the number of HO-1-positive samples and HO-1 immunoreactivity in the cancerous tissues were significantly higher than those in the non-tumor tissues. These results were confirmed at the mRNA level. Interestingly, HO-1 localization was observed in the nucleus, and the rate of nuclear HO-1 in HNSCC was higher than that in non-malignant tissues. Nuclear HO-1 was observed in HNSCC cell lines and increased even further following hemin treatment. Analysis of HO-1 expression and sub-cellular localization in a mouse model of squamous cell carcinoma (SCC) and in human HNSCC revealed that nuclear HO-1 increases with tumor progression. Taken together, these results demonstrate that HO-1 is up-regulated in HNSCC and that nuclear localization of HO-1 is associated with malignant progression in this tumor type.

  11. Health and Safety Considerations Associated with Sodium-Cooled Experimental Nuclear Fuel Dismantlement

    SciTech Connect

    Carvo, Alan E.

    2015-04-01

    Between the mid-1970s and the mid-1980s Sandia National Laboratory constructed eleven experimental assemblies to simulate debris beds formed in a sodium-cooled fast breeder reactor. All but one of the assemblies were irradiated. The experimental assemblies were transferred to the Idaho National Laboratory (INL) in 2007 and 2008 for storage, dismantlement, recovery of the uranium for reuse in the nuclear fuel cycle, and disposal of unneeded materials. This paper addresses the effort to dismantle the assemblies down to the primary containment vessel and repackage them for temporary storage until such time as equipment necessary for sodium separation is in place.

  12. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    SciTech Connect

    Cha, Seho; Lim, Chunghun; Lee, Jae Young; Song, Yoon-Jae; Park, Junsoo; Choe, Joonho; Seo, Taegun

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  13. Complex alternative cytoplasmic protein isoforms of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 generated through noncanonical translation initiation.

    PubMed

    Toptan, Tuna; Fonseca, Lidia; Kwun, Hyun Jin; Chang, Yuan; Moore, Patrick S

    2013-03-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ∼50% of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1(S). Higher-molecular-weight LANA1(S) isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1(S) isoforms initiate downstream within the central repeat 1 domain. LANA1(S) proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.

  14. Expression of DNAJB12 or DNAJB14 Causes Coordinate Invasion of the Nucleus by Membranes Associated with a Novel Nuclear Pore Structure

    PubMed Central

    Goodwin, Edward C.; Motamedi, Nasim; Lipovsky, Alex; Fernández-Busnadiego, Rubén; DiMaio, Daniel

    2014-01-01

    DNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER) that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, which we designate DJANGOS for DNAJ-associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70 and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are evenly distributed underneath the nuclear envelope and are of uniform size in any one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and sheets that connect to the nuclear envelope via a unique configuration of membranes, in which the nuclear pore complex appears anchored exclusively to the outer nuclear membrane, allowing both the inner and outer nuclear membranes to flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS break down rapidly during cell division and reform synchronously in the daughter cell nuclei, demonstrating that they are dynamic structures that undergo coordinate formation and dissolution. Genetic studies showed that the chaperone activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis of these structures will provide insight into nuclear pore formation and function, activities of molecular chaperones, and mechanisms that maintain membrane identity. PMID:24732912

  15. Nuclear and cytoplasmic changes associated with maturation in the vascular cambium of Larix laricina.

    PubMed

    Mellerowicz, E. J.; Riding, R. T.; Greenwood, M. S.

    1995-01-01

    We studied the effects of apical maturation on the vascular cambium of juvenile and mature scions of Larix laricina (Du Roi) K. Koch that had been grafted on seedling rootstocks. Comparisons between the juvenile and mature cambium in nuclear genome size, nuclear shape, DNA concentration, number and volume of nucleoli per nucleus, and concentration of extranuclear RNAs, proteins and insoluble carbohydrates were conducted on four occasions during the annual cycle of cambial activity and dormancy. All investigated variables exhibited strong annual oscillations, whereas differences between the two maturation stages were less prominent. Many of the differences between the two phases could be explained by delayed spring reactivation and accelerated onset of dormancy in the mature cambium compared with the juvenile cambium. At the time of reactivation and during activity, the mature cambium exhibited lower genome size, lower DNA concentration, fewer nucleoli per nucleus and a higher extranuclear concentration of insoluble carbohydrates than the juvenile cambium. The dormant mature cambium contained more extranuclear RNAs than the dormant juvenile cambium. The observed differences provide circumstantial evidence of changes in chromatin organization or functioning, or both, during maturation.

  16. Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer.

    PubMed

    Jögi, Annika; Brennan, Donal J; Rydén, Lisa; Magnusson, Kristina; Fernö, Mårten; Stål, Olle; Borgquist, Signe; Uhlen, Mathias; Landberg, Göran; Påhlman, Sven; Pontén, Fredrik; Jirström, Karin

    2009-12-01

    Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n=1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (P<0.001), small tumors (P<0.001), estrogen receptor (ER) positivity (P<0.001) and Ki-67 negativity (P<0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P=0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors.

  17. Molecular Characterization of the SUMO-1 Modification of RanGAP1 and Its Role in Nuclear Envelope Association

    PubMed Central

    Mahajan, Rohit; Gerace, Larry; Melchior, Frauke

    1998-01-01

    The mammalian guanosine triphosphate (GTP)ase-activating protein RanGAP1 is the first example of a protein covalently linked to the ubiquitin-related protein SUMO-1. Here we used peptide mapping, mass spectroscopy analysis, and mutagenesis to identify the nature of the link between RanGAP1 and SUMO-1. SUMO-1 is linked to RanGAP1 via glycine 97, indicating that the last 4 amino acids of this 101– amino acid protein are proteolytically removed before its attachment to RanGAP1. Recombinant SUMO-1 lacking the last four amino acids is efficiently used for modification of RanGAP1 in vitro and of multiple unknown proteins in vivo. In contrast to most ubiquitinated proteins, only a single lysine residue (K526) in RanGAP1 can serve as the acceptor site for modification by SUMO-1. Modification of RanGAP1 with SUMO-1 leads to association of RanGAP1 with the nuclear envelope (NE), where it was previously shown to be required for nuclear protein import. Sufficient information for modification and targeting resides in a 25-kD domain of RanGAP1. RanGAP1–SUMO-1 remains stably associated with the NE during many cycles of in vitro import. This indicates that removal of RanGAP1 from the NE is not a required element of nuclear protein import and suggests that the reversible modification of RanGAP1 may have a regulatory role. PMID:9442102

  18. Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

    PubMed

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2012-11-01

    Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

  19. High expression level and nuclear localization of Sam68 are associated with progression and poor prognosis in colorectal cancer

    PubMed Central

    2013-01-01

    Background Src-associated in mitosis (Sam68; 68 kDa) has been implicated in the oncogenesis and progression of several human cancers. The aim of this study was to investigate the clinicopathologic significance of Sam68 expression and its subcellular localization in colorectal cancer (CRC). Methods Sam68 expression was examined in CRC cell lines, nine matched CRC tissues and adjacent noncancerous tissues using reverse transcription (RT)-PCR, quantitative RT-PCR and Western blotting. Sam68 protein expression and localization were determined in 224 paraffin-embedded archived CRC samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. Results Sam68 was upregulated in CRC cell lines and CRC, as compared with normal tissues; high Sam68 expression was detected in 120/224 (53.6%) of the CRC tissues. High Sam68 expression correlated significantly with poor differentiation (P = 0.033), advanced T stage (P < 0.001), N stage (P = 0.023) and distant metastasis (P = 0.033). Sam68 nuclear localization correlated significantly with poor differentiation (P = 0.002) and T stage (P =0.021). Patients with high Sam68 expression or Sam68 nuclear localization had poorer overall survival than patients with low Sam68 expression or Sam68 cytoplasmic localization. Patients with high Sam68 expression had a higher risk of recurrence than those with low Sam68 expression. Conclusions Overexpression of Sam68 correlated highly with cancer progression and poor differentiation in CRC. High Sam68 expression and Sam68 nuclear localization were associated with poorer overall survival. PMID:23937454

  20. Nuclear-Cytoplasmic Conflict in Pea (Pisum sativum L.) Is Associated with Nuclear and Plastidic Candidate Genes Encoding Acetyl-CoA Carboxylase Subunits

    PubMed Central

    Bogdanova, Vera S.; Zaytseva, Olga O.; Mglinets, Anatoliy V.; Shatskaya, Natalia V.; Kosterin, Oleg E.; Vasiliev, Gennadiy V.

    2015-01-01

    In crosses of wild and cultivated peas (Pisum sativum L.), nuclear-cytoplasmic incompatibility frequently occurs manifested as decreased pollen fertility, male gametophyte lethality, sporophyte lethality. High-throughput sequencing of plastid genomes of one cultivated and four wild pea accessions differing in cross-compatibility was performed. Candidate genes for involvement in the nuclear-plastid conflict were searched in the reconstructed plastid genomes. In the annotated Medicago truncatula genome, nuclear candidate genes were searched in the portion syntenic to the pea chromosome region known to harbor a locus involved in the conflict. In the plastid genomes, a substantial variability of the accD locus represented by nucleotide substitutions and indels was found to correspond to the pattern of cross-compatibility among the accessions analyzed. Amino acid substitutions in the polypeptides encoded by the alleles of a nuclear locus, designated as Bccp3, with a complementary function to accD, fitted the compatibility pattern. The accD locus in the plastid genome encoding beta subunit of the carboxyltransferase of acetyl-coA carboxylase and the nuclear locus Bccp3 encoding biotin carboxyl carrier protein of the same multi-subunit enzyme were nominated as candidate genes for main contribution to nuclear-cytoplasmic incompatibility in peas. Existence of another nuclear locus involved in the accD-mediated conflict is hypothesized. PMID:25789472

  1. Pakistan’s Nuclear Weapons: Proliferation and Security Issues

    DTIC Science & Technology

    2009-04-01

    2007,” ibid.; SIPRI Yearbook 2007. 5 “Nuclear Notebook,” ibid. 6 “Global Fissile Material Report 2007,” International Panel on Fissile Materials...State for Foreign and Commonwealth Affairs David Miliband told the Charlie Rose Show December 15, 2008, that Islamabad’s nuclear weapons “are under...Nuclear Weapons in Pakistan,” Pakistan Security Research Unit Brief Number 22, University of Bradford, November 18, 2007. Available at http

  2. The Herpesvirus Associated Ubiquitin Specific Protease, USP7, Is a Negative Regulator of PML Proteins and PML Nuclear Bodies

    PubMed Central

    Sarkari, Feroz; Wang, Xueqi; Nguyen, Tin; Frappier, Lori

    2011-01-01

    The PML tumor suppressor is the founding component of the multiprotein nuclear structures known as PML nuclear bodies (PML-NBs), which control several cellular functions including apoptosis and antiviral effects. The ubiquitin specific protease USP7 (also called HAUSP) is known to associate with PML-NBs and to be a tight binding partner of two herpesvirus proteins that disrupt PML NBs. Here we investigated whether USP7 itself regulates PML-NBs. Silencing of USP7 was found to increase the number of PML-NBs, to increase the levels of PML protein and to inhibit PML polyubiquitylation in nasopharyngeal carcinoma cells. This effect of USP7 was independent of p53 as PML loss was observed in p53-null cells. PML-NBs disruption was induced by USP7 overexpression independently of its catalytic activity and was induced by either of the protein interaction domains of USP7, each of which localized to PML-NBs. USP7 also disrupted NBs formed from some single PML isoforms, most notably isoforms I and IV. CK2α and RNF4, which are known regulators of PML, were dispensable for USP7-associated PML-NB disruption. The results are consistent with a novel model of PML regulation where a deubiquitylase disrupts PML-NBs through recruitment of another cellular protein(s) to PML NBs, independently of its catalytic activity. PMID:21305000

  3. The herpesvirus associated ubiquitin specific protease, USP7, is a negative regulator of PML proteins and PML nuclear bodies.

    PubMed

    Sarkari, Feroz; Wang, Xueqi; Nguyen, Tin; Frappier, Lori

    2011-01-31

    The PML tumor suppressor is the founding component of the multiprotein nuclear structures known as PML nuclear bodies (PML-NBs), which control several cellular functions including apoptosis and antiviral effects. The ubiquitin specific protease USP7 (also called HAUSP) is known to associate with PML-NBs and to be a tight binding partner of two herpesvirus proteins that disrupt PML NBs. Here we investigated whether USP7 itself regulates PML-NBs. Silencing of USP7 was found to increase the number of PML-NBs, to increase the levels of PML protein and to inhibit PML polyubiquitylation in nasopharyngeal carcinoma cells. This effect of USP7 was independent of p53 as PML loss was observed in p53-null cells. PML-NBs disruption was induced by USP7 overexpression independently of its catalytic activity and was induced by either of the protein interaction domains of USP7, each of which localized to PML-NBs. USP7 also disrupted NBs formed from some single PML isoforms, most notably isoforms I and IV. CK2α and RNF4, which are known regulators of PML, were dispensable for USP7-associated PML-NB disruption. The results are consistent with a novel model of PML regulation where a deubiquitylase disrupts PML-NBs through recruitment of another cellular protein(s) to PML NBs, independently of its catalytic activity.

  4. Transcriptional activation by the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen is facilitated by an N-terminal chromatin-binding motif.

    PubMed

    Wong, Lai-Yee; Matchett, Gerald A; Wilson, Angus C

    2004-09-01

    In immunocompromised patients, infection with Kaposi's sarcoma-associated herpesvirus (KSHV) can give rise to Kaposi's sarcoma and several lymphoproliferative disorders. In these tumors, KSHV establishes a latent infection in many of the rapidly proliferating and morphologically abnormal cells. Only a few viral gene products are expressed by the latent virus, and one of the best characterized is the latency-associated nuclear antigen (LANA), a nuclear protein required for the maintenance of viral episomal DNA in the dividing host cell. LANA can also activate or repress an assortment of cellular and viral promoters and may contribute to pathogenesis by allowing the proliferation and survival of host cells. Here we show that activation of the human E2F1 and cyclin-dependent kinase-2 (CDK2) promoters requires elements from both the N- and C-terminal regions of LANA. Deletion of the first 22 amino acids, which are necessary for episome tethering, does not affect nuclear localization but significantly reduces transactivation. Within the deleted peptide, we have identified a short sequence, termed the chromatin-binding motif (CBM), that binds tightly to interphase and mitotic chromatin. A second chromatin-binding activity resides in the C terminus but is not sufficient for optimal transactivation. Alanine substitutions within the CBM reveal a close correlation between the transactivation and chromatin binding activities, implying a mechanistic link. In contrast to promoter activation, we find that the 223 amino acids of the LANA C terminus are sufficient to inhibit p53-mediated activation of the human BAX promoter, indicating that the CBM is not required for all transcription-related functions.

  5. Panel report on coupled thermo-mechanical-hydro-chemical processes associated with a nuclear waste repository

    SciTech Connect

    Tsang, C.F.; Mangold, D.C.

    1984-07-01

    Four basic physical processes, thermal, hydrological, mechanical and chemical, are likely to occur in 11 different types of coupling during the service life of an underground nuclear waste repository. A great number of coupled processes with various degrees of importance for geological repositories were identified and arranged into these 11 types. A qualitative description of these processes and a tentative evaluation of their significance and the degree of uncertainty in prediction is given. Suggestions for methods of investigation generally include, besides theoretical work, laboratory and large scale field testing. Great efforts of a multidisciplinary nature are needed to elucidate details of several coupled processes under different temperature conditions in different geological formations. It was suggested that by limiting the maximum temperature to 100{sup 0}C in the backfill and in the host rock during the whole service life of the repository the uncertainties in prediction of long-term repository behavior might be considerably reduced.

  6. Apoptosis and nuclear factor-kappa B: a tale of association and dissociation.

    PubMed

    Aggarwal, B B

    2000-10-15

    It is not clear why on treatment with certain killer cytokines or chemotherapeutic agents, some cells undergo apoptosis while others do not. The delineation of sensitivity/resistance pathways should provide a more specific therapy for cancer and other hyperproliferative diseases. Most cells die either by apoptosis or by necrosis. The biochemical pathway that mediates these two modes of cell death has recently been described. The nuclear factor (NF)-kappa B and the genes regulated by this transcription factor have been shown to play a critical role in induction of resistance to killer agents. Thus, inhibitors of NF-kappa B activation have a potential in overcoming resistance to apoptosis induced by various agents. The evidence for and against such a notion is discussed.

  7. Deep sequencing unearths nuclear mitochondrial sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants.

    PubMed

    Petruzzella, Vittoria; Carrozzo, Rosalba; Calabrese, Claudia; Dell'Aglio, Rosa; Trentadue, Raffaella; Piredda, Roberta; Artuso, Lucia; Rizza, Teresa; Bianchi, Marzia; Porcelli, Anna Maria; Guerriero, Silvana; Gasparre, Giuseppe; Attimonelli, Marcella

    2012-09-01

    Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences.

  8. [Nuclear gene involves in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation].

    PubMed

    Zhao, Su Ying; Zhang, Hai Jun; Xu, Chun Hong; Shan, Xiang Nian

    2006-02-01

    The human mitochondrial 12S rRNA gene mutation at position 1555 associated with non-syndromic deafness and aminoglycoside-induced deafness. Family of Huaiyin in Jiangsu is one of the biggest non-syndromic deafness family in the world. In this family, deafness is maternally inherited. After establishing immortal lymphoblastoid cell lines of the family by EB virus, we analysed 17 lymphoblastoid cell lines derived, respectively, from symptomatic, asymptomatic and controll members of the family. Compared with control members, symptomatic and asymptomatic members both exhibited significant decreases in the rate of growth as well as in the rates of mitochondrial protein synthesis. But the extent of decreases is different and the severity of mitochondrial defect is related with its clinical phenotype. These results supported that the nuclear factor involves in the phenotypic manifestation of the non-syndromic deafness associated with the A1555G mutation.

  9. Mutations in the Hepatocyte Nuclear Factor-1β Gene Are Associated with Familial Hypoplastic Glomerulocystic Kidney Disease

    PubMed Central

    Bingham, Coralie; Bulman, Michael P.; Ellard, Sian; Allen, Lisa I. S.; Lipkin, Graham W.; Hoff, William G. van't; Woolf, Adrian S.; Rizzoni, Gianfranco; Novelli, Giuseppe; Nicholls, Anthony J.; Hattersley, Andrew T.

    2001-01-01

    Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)–1β have been associated with early-onset diabetes and nondiabetic renal disease—particularly renal cystic disease. We investigated a possible role for the HNF-1β gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1β gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1β mutations. PMID:11085914

  10. Characterization of a nuclear localization signal in the C-terminus of the adeno-associated virus Rep68/78 proteins

    SciTech Connect

    Cassell, Geoffrey D.; Weitzman, Matthew D. . E-mail: weitzman@salk.edu

    2004-10-01

    Adeno-associated virus (AAV) replicates in the nucleus of infected cells, and therefore multiple nuclear import events are required for productive infection. We analyzed nuclear import of the viral Rep proteins and characterized a nuclear localization signal (NLS) in the C-terminus. We demonstrate that basic residues in this region constitute an NLS that is transferable and mediates interaction with the nuclear import receptor importin {alpha} in vitro. Mutant Rep proteins are predominantly cytoplasmic and are severely compromised for interactions with importin {alpha}, but retain their enzymatic functions in vitro. Interestingly, mutations of the NLS had significantly less effect on importin {alpha} interaction and replication in the context of Rep78 than when incorporated into the Rep68 protein. Together, our results demonstrate that a bipartite NLS exists in the shared part of Rep68 and Rep78, and suggest that an alternate entry mechanism may also contribute to nuclear localization of the Rep78 protein.

  11. David Malament and the Conventionality of Simultaneity: A Reply

    NASA Astrophysics Data System (ADS)

    Grünbaum, Adolf

    2010-10-01

    In 1977, David Malament proved the valuable technical result that the simultaneity relation of standard synchrony ɛ=1/2 with respect to an inertial observer O is uniquely definable in terms of the relation κ of causal connectibility. And he claimed that this definability undermines my own version of the conventionality of metrical simultaneity within an inertial frame. But Malament’s proof depends on the imposition of several supposedly “innocuous” constraints on any candidate for the simultaneity relation relative to O. Relying on Allen I. Janis’s 1983 challenge to one of these constraints, I argue that Malament’s technical result did not undermine my philosophical construal of the ontological status of relative metrical simultaneity. Furthermore, I show that (a) Michael Friedman’s peremptorily substantivalist critique of my conception, which Malament endorses, is ill-founded, and (b) if Malament had succeeded in discrediting my own conventionalist version of metrical simultaneity, he would likewise have invalidated Einstein’s pioneering version of it.

  12. Sir David Brewster's changing ideas on the plurality of worlds

    NASA Astrophysics Data System (ADS)

    de Asúa, Miguel

    2006-06-01

    In the course of his long life the Scottish physicist David Brewster wrote copiously about the plurality of worlds. More Worlds than One (1854), perhaps his strongest statement on the question, was written as an answer to William Whewell's On the Plurality of Worlds (1853), which argued that life was a privilege of the Earth. Brewster's ideas changed drastically along the years in many crucial issues such as the habitability of the Sun and the Moon, the possibility that extraterrestrials could be different from humans, and the occupation of the Earth by intelligent races in the distant past. This paper succinctly surveys Brewster's main lines of thought about the plurality of worlds underlining the significance of his first two articles devoted exclusively to this topic. They were published in 1838 in The Monthly Chronicle, and affirm the habitability of the planets while denying that of the Moon. As is the case with many Victorian scientists, belief in pluralism was for Brewster part and parcel of a complex of ideas and attitudes in which it is hard to distinguish science from religion. I shall argue that a fair number of the shifting opinions and inconsistencies detectable in Brewster's ideas on the plurality of worlds can be attributed to the fact that these were used as pliable apologetic instruments in his scientific writings, many of which are permeated by strong religious concerns.

  13. DAVID-WS: a stateful web service to facilitate gene/protein list analysis.

    PubMed

    Jiao, Xiaoli; Sherman, Brad T; Huang, Da Wei; Stephens, Robert; Baseler, Michael W; Lane, H Clifford; Lempicki, Richard A

    2012-07-01

    The database for annotation, visualization and integrated discovery (DAVID), which can be freely accessed at http://david.abcc.ncifcrf.gov/, is a web-based online bioinformatics resource that aims to provide tools for the functional interpretation of large lists of genes/proteins. It has been used by researchers from more than 5000 institutes worldwide, with a daily submission rate of ∼1200 gene lists from ∼400 unique researchers, and has been cited by more than 6000 scientific publications. However, the current web interface does not support programmatic access to DAVID, and the uniform resource locator (URL)-based application programming interface (API) has a limit on URL size and is stateless in nature as it uses URL request and response messages to communicate with the server, without keeping any state-related details. DAVID-WS (web service) has been developed to automate user tasks by providing stateful web services to access DAVID programmatically without the need for human interactions. The web service and sample clients (written in Java, Perl, Python and Matlab) are made freely available under the DAVID License at http://david.abcc.ncifcrf.gov/content.jsp?file=WS.html.

  14. Heterochromatic self-association, a determinant of nuclear organization, does not require sequence homology in Drosophila.

    PubMed Central

    Sage, Brian T; Csink, Amy K

    2003-01-01

    Chromosomes of higher eukaryotes contain blocks of heterochromatin that can associate with each other in the interphase nucleus. A well-studied example of heterochromatic interaction is the brown(Dominant) (bwD) chromosome of D. melanogaster, which contains an approximately 1.6-Mbp insertion of AAGAG repeats near the distal tip of chromosome 2. This insertion causes association of the tip with the centric heterochromatin of chromosome 2 (2h), which contains megabases of AAGAG repeats. Here we describe an example, other than bwD, in which distally translocated heterochromatin associates with centric heterochromatin. Additionally, we show that when a translocation places bwD on a different chromosome, bwD tends to associate with the centric heterochromatin of this chromosome, even when the chromosome contains a small fraction of the sequence homology present elsewhere. To further test the importance of sequence homology in these interactions, we used interspecific mating to introgress the bwD allele from D. melanogaster into D. simulans, which lacks the AAGAG on the autosomes. We find that D. simulans bwD associates with 2h, which lacks the AAGAG sequence, while it does not associate with the AAGAG containing X chromosome heterochromatin. Our results show that intranuclear association of separate heterochromatic blocks does not require that they contain the same sequence. PMID:14668374

  15. The PML-nuclear inclusion of human supraoptic neurons: a new compartment with SUMO-1- and ubiquitin-proteasome-associated domains.

    PubMed

    Villagra, Nuria T; Navascues, Joaquin; Casafont, Iñigo; Val-Bernal, J Fernando; Lafarga, Miguel; Berciano, Maria T

    2006-01-01

    It is well known that the cell nucleus is organized in structural and functional compartments involved in transcription, RNA processing and protein modifications such as conjugation with SUMO-1 and proteolysis. Promyelocytic leukaemia (PML) bodies are dynamic nuclear structures that concentrate PML protein, SUMO-1 and several sumoylated and non-sumoylated protein regulators of nuclear functions. PML bodies and their associated CBP has been involved in neuronal survival. By light and electron microscopy immunocytochemistry and in situ hybridization we reported the presence, in non-pathological conditions, of a large PML-nuclear inclusion (PML-NI) in human supraoptic neurons. This inclusion appears as a single nuclear structure composed of a capsule enriched in PML, SUMO-1 and CBP proteins and a central lattice of filaments immunoreactive for class III beta-tubulin, ubiquitinated proteins and proteasomes. Furthermore, the PML-NI concentrates the SUMO-conjugating enzyme E2 (UBC9). The PML-NI may be considered a nuclear factory involved in sumoylation and proteolysis via ubiquitin-proteasome system, two nuclear pathways engaged in the control of the nucleoplasmic concentration of active transcriptional regulators. Interestingly, the structural and molecular organization of the PML-NI is related to the Marinesco bodies, age-associated ubiquitinated intranuclear inclusions, and to the intranuclear rodlets enriched in class III beta-tubulin, which are nuclear structures markedly decreased in Alzheimer's disease.

  16. Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer.

    PubMed

    Carpenter, B; McKay, M; Dundas, S R; Lawrie, L C; Telfer, C; Murray, G I

    2006-10-09

    Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which has several different cellular roles including transcription, mRNA shuttling, RNA editing and translation. Several reports implicate hnRNP K having a role in tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified as being overexpressed in this type of cancer. Immunohistochemistry with a monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue microarray, confirmed that hnRNP K was overexpressed in colorectal cancer (P<0.001) and also showed that hnRNP K had an aberrant subcellular localisation in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in colorectal cancer the protein localised both in the cytoplasm and the nucleus. There were significant increases in both nuclear (P=0.007) and cytoplasmic (P=0.001) expression of hnRNP K in Dukes C tumours compared with early stage tumours. In Dukes C patient's good survival was associated with increased hnRNP K nuclear expression (P=0.0093). To elaborate on the recent observation that hnRNP K is regulated by p53, the expression profiles of these two proteins were also analysed. There was no correlation between hnRNP K and p53 expression, however, patients who presented tumours that were positive for hnRNP K and p53 had a poorer survival outcome (P=0.045).

  17. Compensatory increases in nuclear PGC1alpha protein are primarily associated with subsarcolemmal mitochondrial adaptations in ZDF rats.

    PubMed

    Holloway, Graham P; Gurd, Brendon J; Snook, Laelie A; Lally, Jamie; Bonen, Arend

    2010-04-01

    We examined in insulin-resistant muscle if, in contrast to long-standing dogma, mitochondrial fatty acid oxidation is increased and whether this is attributed to an increased nuclear content of peroxisome proliferator-activated receptor (PPAR) gamma coactivator (PGC) 1alpha and the adaptations of specific mitochondrial subpopulations. Skeletal muscles from male control and Zucker diabetic fatty (ZDF) rats were used to determine 1) intramuscular lipid distribution, 2) subsarcolemmal and intermyofibrillar mitochondrial morphology, 3) rates of palmitate oxidation in subsarcolemmal and intermyofibrillar mitochondria, and 4) the subcellular localization of PGC1alpha. Electotransfection of PGC1alpha cDNA into lean animals tested the notion that increased nuclear PGC1alpha preferentially targeted subsarcolemmal mitochondria. Transmission electron microscope analysis revealed that in ZDF animals the number (+50%), width (+69%), and density (+57%) of subsarcolemmal mitochondria were increased (P < 0.05). In contrast, intermyofibrillar mitochondria remained largely unchanged. Rates of palmitate oxidation were approximately 40% higher (P < 0.05) in ZDF subsarcolemmal and intermyofibrillar mitochondria, potentially as a result of the increased PPAR-targeted proteins, carnitine palmitoyltransferase-I, and fatty acid translocase (FAT)/CD36. PGC1alpha mRNA and total protein were not altered in ZDF animals; however, a greater (approximately 70%; P < 0.05) amount of PGC1alpha was located in nuclei. Overexpression of PGC1alpha only increased subsarcolemmal mitochondrial oxidation rates. In ZDF animals, intramuscular lipids accumulate in the intermyofibrillar region (increased size and number), and this is primarily associated with increased oxidative capacity in subsarcolemmal mitochondria (number, size, density, and oxidation rates). These changes may result from an increased nuclear content of PGC1alpha, as under basal conditions, overexpression of PGC1alpha appears to target

  18. Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

    PubMed Central

    Herencia, Carmen; Martínez-Moreno, Julio M.; Herrera, Concepción; Corrales, Fernando; Santiago-Mora, Raquel; Espejo, Isabel; Barco, Monserrat; Almadén, Yolanda; de la Mata, Manuel; Rodríguez-Ariza, Antonio; Muñoz-Castañeda, Juan R.

    2012-01-01

    Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype. PMID:22506042

  19. Aryl hydrocarbon receptor nuclear translocator is associated with tumor growth and progression of hepatocellular carcinoma.

    PubMed

    Liang, Ying; Li, Wei-Wei; Yang, Bi-Wei; Tao, Zhong-Hua; Sun, Hui-Chuan; Wang, Lu; Xia, Jing-Lin; Qin, Lun-Xiu; Tang, Zhao-You; Fan, Jia; Wu, Wei-Zhong

    2012-04-15

    bHLH/PAS proteins play important roles in tumor progression. Lost or reduced expression of single-minded homolog 2 (SIM) as well as aryl hydrocarbon receptor repressor (AHRR) has been observed in cancerous human tissues. Here, we investigated the role of aryl hydrocarbon receptor nuclear translocator (ARNT), another bHLH/PAS protein, in hepatocellular carcinoma (HCC). Using tissue microarray and immunohistochemistry, we found that intratumoral ARNT was inversely correlated with time to recurrence and overall survival of HCC patients after resection. Knockdown of ARNT in HepG2, HCCLM3 and HCCLM6 cells significantly shortened cell doubling time, increased S-phase cell populations and accelerated in vivo HCCLM6 growth and metastasis. After ARNT expression was rescued, prolonged cell doubling time and decreased S-phase cell populations were observed in HepG2, HCCLM3 and HCCLM6 cells. And, HCCLM6 growth and metastasis in vivo were remarkably inhibited. Screening by quantitative reverse-transcription PCR and PCR arrays revealed that cyclin E1, CDK2, Fos and Jun were negatively regulated by ARNT, whereas CDKN1C, CNKN2A, CDKN2B, MAPK11 and MAPK14 were positively regulated in HCC. According to the results of immunoprecipitation assay, both ARNT/ARNT and ARNT/AHRR complexes were clearly formed in HCCLM6 xenograft with increased ARNT expression. In summary, ARNT is an important regulator of HCC growth and metastasis and could be a promising prognostic candidate in HCC patients. Copyright © 2011 UICC.

  20. Geo-Space observation of atmospheric environmental effects associated with 2011 Fukushima nuclear accident

    NASA Astrophysics Data System (ADS)

    Pulinets, Sergey; Ouzounov, Dimitar; Hernandez-Pajares, Manuel; Hattori, Katsumi; Garcia-Rigo, Alberto

    2014-05-01

    Our approach of using multiple geo-space observation is based on the LAIC (Lithosphere- Atmosphere- Ionosphere Coupling) model and the gained experience during similar analysis of Three-Mile Island and Chernobyl accidents. We do collect a unique dataset of geophysical data for the period around the time of the most active phase of Fukushima explosions (from 12 March till 31 March, 71-90 DOY). We analyzed following data sets: (i) ground temperature and relative humidity data from the JMA network of Japan, (ii) satellite meteorological data and assimilative models to obtain the integrated water vapor chemical potential; (iii) the infrared emission on the top of atmosphere measured by NOAA and GEOS satellites estimated as Outgoing Longwave Radiation; and (iv) multiple ionospheric measurements , including ground based ionosondes, GPS vTEC from GEONET network, COSMIC/FORMOSAT constellation occultation data, JASON satellite TEC measurements, and tomography reconstruction technique to obtain 3D distribution of electron concentration around the Fukushima power plant. As a result we were able to detect the anomalies in different geophysical parameters representing the dynamics of the Fukushima nuclear accident development and the effects on the atmospheric environment. Their temporal evolution demonstrates the synergy in different atmospheric anomalies development what implies the existence of the common physical mechanism described by the LAIC model.

  1. Human diabetes associated with defects in nuclear regulatory proteins for the insulin receptor gene.

    PubMed Central

    Brunetti, A; Brunetti, L; Foti, D; Accili, D; Goldfine, I D

    1996-01-01

    The control of gene transcription is mediated by sequence-specific DNA-binding proteins (trans-acting factors) that bind to upstream regulatory elements (cis elements). We have previously identified two DNA-binding proteins that specifically interact with two unique AT-rich sequences of the 5' regulatory region of the insulin receptor gene which have in vivo promoter activity. Herein we have investigated the expression of these DNA-binding proteins in cells from two unrelated patients with insulin resistance and non-insulin-dependent diabetes mellitus. In these patients, the insulin receptor gene was normal. In EBV-transformed lymphoblasts from both patients, insulin receptor mRNA levels and insulin receptor expression were decreased. The expression of nuclear-binding proteins for the 5' regulatory region of the insulin receptor gene was markedly reduced, and this defect paralleled the decrease in insulin receptor protein expression. These studies indicate that DNA-binding proteins to the regulatory region of the insulin receptor gene are important for expression of the insulin receptor. Further, they suggest that in affected individuals, defects in the expression of these proteins may cause decreased insulin receptor expression and insulin resistance. PMID:8550844

  2. Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins.

    PubMed

    Lindberg, Sofia Rondin; Olsson, André; Persson, Ann-Maj; Olsson, Inge

    2003-12-01

    The eight-twenty-one (ETO) homologues, represented by ETO, myeloid transforming gene-related protein 1 (MTGR1) and myeloid transforming gene chromosome 16 (MTG16), are nuclear repressor proteins. ETO is part of the fusion protein acute myeloid leukaemia (AML)1-ETO, resulting from the translocation (8;21). Similarly, MTG16 is disrupted to become part of AML1/MTG16 in t(16;21). The aberrant expression of these chimeras could affect interplay between ETO homologues and contribute to the leukaemogenic process. We investigated possible interactions between the ETO homologues. Ectopic co-expression in COS-cells resulted in heterodimerisation of the various ETO homologues suggesting that they may co-operate. Similarly, the chimeric oncoprotein AML1-ETO interacted with both MTGR1 and MTG16. However, results from cell lines endogenously expressing more than one ETO homologue did not demonstrate co-precipitation. Results from IP-Western and size determination by gel filtration of deletion mutants expressed in COS-cells, indicated an important role of the HHR domain for oligomerisation. A role was also suggested for the Nervy domain in the homologue interactions. Our results suggest that ETO homologues can interact with each other as well as with AML1-ETO, although it is unclear as to what extent these interactions occur in vivo.

  3. Preliminary issues associated with the next generation nuclear plant intermediate heat exchanger design

    NASA Astrophysics Data System (ADS)

    Natesan, K.; Moisseytsev, A.; Majumdar, S.

    2009-07-01

    The Next Generation Nuclear Plant, with emphasis on production of both electricity and hydrogen, involves helium as the coolant and a closed-cycle gas turbine for power generation with a core outlet/gas turbine inlet temperature of 850-950 °C. In this concept, an intermediate heat exchanger is used to transfer the heat from primary helium from the core to the secondary fluid, which can be helium, a nitrogen/helium mixture, or a molten salt. This paper assesses the issues pertaining to shell-and-tube and compact heat exchangers. A detailed thermal-hydraulic analysis was performed to calculate heat transfer, temperature distribution, and pressure drop inside both printed circuit and shell-and-tube heat exchangers. The analysis included evaluation of the role of key process parameters, geometrical factors in heat exchanger designs, and material properties of structural alloys. Calculations were performed for helium-to-helium, helium-to-helium/nitrogen, and helium-to-salt heat exchangers.

  4. Superovulation in red deer (Cervus elaphus) and Père David's deer (Elaphurus davidianus), and fertilization rates following artificial insemination with Père David's deer semen.

    PubMed

    Argo, C M; Jabbour, H N; Goddard, P J; Webb, R; Loudon, A S

    1994-03-01

    Two comparative studies were undertaken using adult, female red and Père David's deer to examine the ovulatory response of these animals to a superovulation regimen and fertilization rates following inter- and intraspecific laparoscopic insemination. In Expt 1 six Père David's deer and 12 red deer hinds were treated during the breeding season with an intravaginal progesterone-impregnated controlled internal drug release device (CIDR) for 14 days, with 200 iu pregnant mares' serum gonadotrophin (PMSG) administered 72 h before the device was withdrawn and eight injections of ovine FSH given at 12 h intervals starting at the time of PMSG administration. Oestrous behaviour began one day after CIDR device withdrawal (Père David's deer: 24.00 +/- 2.32 h; red deer: 24.60 +/- 2.23 h). The duration of oestrus was greater in Père David's deer than in red deer (17.50 +/- 1.43 h and 8.25 +/- 3.25 h, respectively, P < 0.001). The peak LH surge of Père David's deer was 68.65 +/- 4.74 ng ml-1 occurring 29.00 +/- 2.41 h after removal of the CIDR devices. In comparison, the peak LH surge in red deer was 17.09 +/- 3.64 ng ml-1 (P < 0.001), occurring 24.00 +/- 0.00 h after CIDR device withdrawal. Pre-surge concentrations of LH were also greater (P < 0.001) in Père David's deer (1.37 +/- 0.11 ng ml-1) than in red deer hinds (0.41 +/- 0.02 ng ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families

    PubMed Central

    Xu, X.-H.; Xiong, D.-H.; Liu, X.-G.; Guo, Y.; Chen, Y.; Zhao, J.; Recker, R. R.; Deng, H.-W.

    2010-01-01

    Summary This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. Introduction CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of ~44% found in this study), but the relevant genetic study is still rather scarce. Methods Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. Results Significant associations with CSI were found with two SNPs (rs222029, P=0.0019; rs222020, P=0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. Conclusions Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males. PMID:19543766

  6. CESAR5.3: An Industrial Tool for Nuclear Fuel and Waste Characterization with Associated Qualification - 12067

    SciTech Connect

    Vidal, Jean-Marc; Eschbach, Romain; Launay, Agnes; Binet, Christophe; THRO, Jean-Francois

    2012-07-01

    CEA and AREVA-NC have developed and used a depletion code named CESAR for 30 years. This user-friendly industrial tool provides fast characterizations for all types of nuclear fuel (PWR / UOX or MOX or reprocess Uranium, BWR / UOX or MOX, MTR and SFR) and the wastes associated. CESAR can evaluate 100 heavy nuclides, 200 fission products and 150 activation products (with Helium and Tritium formation). It can also characterize the structural material of the fuel (Zircalloy, stainless steel, M5 alloy). CESAR provides depletion calculations for any reactor irradiation history and from 3 months to 1 million years of cooling time. CESAR5.3 is based on the latest calculation schemes recommended by the CEA and on an international nuclear data base (JEFF-3.1.1). It is constantly checked against the CEA referenced and qualified depletion code DARWIN. CESAR incorporates the CEA qualification based on the dissolution analyses of fuel rod samples and the 'La Hague' reprocessing plant feedback experience. AREVA-NC uses CESAR intensively at 'La Hague' plant, not only for prospective studies but also for characterizations at different industrial facilities all along the reprocessing process and waste conditioning (near 150 000 calculations per year). CESAR is the reference code for AREVA-NC. CESAR is used directly or indirectly with other software, data bank or special equipment in many parts of the La Hague plants. The great flexibility of CESAR has rapidly interested other projects. CESAR became a 'tool' directly integrated in some other softwares. Finally, coupled with a Graphical User Interface, it can be easily used independently, responding to many needs for prospective studies as a support for nuclear facilities or transport. An English version is available. For the principal isotopes of U and Pu, CESAR5 benefits from the CEA experimental validation for the PWR UOX fuels, up to a burnup of 60 GWd/t and for PWR MOX fuels, up to 45 GWd/t. CESAR version 5.3 uses the CEA

  7. Life Cycle of a Large Telescope: the David Dunlap Observatory

    NASA Astrophysics Data System (ADS)

    Jarrell, Richard

    2009-01-01

    When it went into operation in 1935, the 74-inch reflector at the David Dunlap Observatory was the world's second largest and most sophisticated telescope. Designed specifically for stellar spectroscopy, almost all work performed with it until the early 1950s was limited to that specialty. Most University of Toronto staff were expected to contribute to the observatory's programme. However, as the staff expanded and newer research specialties were introduced, the telescope had to be refitted with new auxiliary equipment, or not be used at all. By the late 1960s, the observatory's night sky began to deteriorate due to light pollution from uncontrolled urban growth. While limited work could be performed into the 1990s, the telescope was no longer considered "large” far more powerful, versatile instruments at much superior sites were by then available. That Toronto astronomers had moved on can be demonstrated from their publication records. The end came in 2008 when the University of Toronto decided that the land's value could be used to support astronomical research in a broader sense. In response, the community, which had ignored the observatory for most of its history, and a few dissident astronomers, strongly defended its survival on a number of grounds. The narrative suggests a number of life-cycle stages: 1) maximum use of the instrument due to superior environmental and technical conditions, plus staff homogeneity; 2) application of new technologies to extend the instrument's capability in the face of diversifying research interests and decaying environmental factors; 3) fading value due to obsolescence and poor environmental factors; 4) death or metamorphosis (such as becoming an educational or historical institution). It appears that these phases apply to a number of historical cases. It is not clear, for the Dunlap Observatory, how the fourth phase will play out.

  8. Preliminary issues associated with the next generation nuclear plant intermediate heat exchanger design.

    SciTech Connect

    Natesan, K.; Moisseytsev, A.; Majumdar, S.; Shankar, P. S.; Nuclear Engineering Division

    2007-04-05

    The Next Generation Nuclear Plant (NGNP), which is an advanced high temperature gas reactor (HTGR) concept with emphasis on production of both electricity and hydrogen, involves helium as the coolant and a closed-cycle gas turbine for power generation with a core outlet/gas turbine inlet temperature of 900-1000 C. In the indirect cycle system, an intermediate heat exchanger is used to transfer the heat from primary helium from the core to the secondary fluid, which can be helium, nitrogen/helium mixture, or a molten salt. The system concept for the vary high temperature reactor (VHTR) can be a reactor based on the prismatic block of the GT-MHR developed by a consortium led by General Atomics in the U.S. or based on the PBMR design developed by ESKOM of South Africa and British Nuclear Fuels of U.K. This report has made a preliminary assessment on the issues pertaining to the intermediate heat exchanger (IHX) for the NGNP. Two IHX designs namely, shell and tube and compact heat exchangers were considered in the assessment. Printed circuit heat exchanger, among various compact heat exchanger (HX) designs, was selected for the analysis. Irrespective of the design, the material considerations for the construction of the HX are essentially similar, except may be in the fabrication of the units. As a result, we have reviewed in detail the available information on material property data relevant for the construction of HX and made a preliminary assessment of several relevant factors to make a judicious selection of the material for the IHX. The assessment included four primary candidate alloys namely, Alloy 617 (UNS N06617), Alloy 230 (UNS N06230), Alloy 800H (UNS N08810), and Alloy X (UNS N06002) for the IHX. Some of the factors addressed in this report are the tensile, creep, fatigue, creep fatigue, toughness properties for the candidate alloys, thermal aging effects on the mechanical properties, American Society of Mechanical Engineers (ASME) Code compliance

  9. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    PubMed

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  10. PML-associated repressor of transcription (PAROT), a novel KRAB-zinc finger repressor, is regulated through association with PML nuclear bodies

    SciTech Connect

    Fleischer, Sandra; Wiemann, Stefan; Will, Hans; Hofmann, Thomas G. . E-mail: t.hofmann@dkfz.de

    2006-04-01

    Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional regulation. Here we identify a novel transcriptional repressor, PML-associated repressor of transcription (PAROT), which is regulated in its repressor activity through recruitment to PML-NBs. PAROT is a Krueppel-associated box ( KRAB) zinc-finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a linker domain and 8 tandemly repeated C{sub 2}H{sub 2}-ZNF motifs at its carboxy terminus. Consistent with its domain structure, when tethered to DNA, PAROT represses transcription, and this is partially released by the HDAC inhibitor trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1 (HP1) family and with transcriptional intermediary factor-1{beta}/KRAB-associated protein 1 (TIF-1{beta}/KAP1), a transcriptional corepressor for the KRAB-ZNF family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently recruits PAROT and TIF-1{beta} from heterochromatin to PML-NBs. PML-NB recruitment of PAROT partially releases its transcriptional repressor activity, indicating that PAROT can be regulated through subnuclear compartmentalization. Taken together, our data identify a novel transcriptional repressor and provide evidence for its regulation through association with PML-NBs.

  11. Beyond 2012: Why the World Won't End A Discussion with Dr. David Morrison

    NASA Image and Video Library

    2012-12-18

    Dr. David Morrison, Astrobiologist and Senior Scientist at NASA Ames Research Center, addresses several theories that the world will end or face some kind of cosmic cataclysm on Friday December 21, 2012. Also known as the Doomsday Prophecy.

  12. Astronaut David Wolf draws blood from Martin Fettman for SLS-2 investigations

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Inside the science module aboard the Earth-orbiting Space Shuttle Columbia, Astronaut David A. Wolf draws blood from payload specialists Martin J. Fettman, DVM. Blood samples from crew members are critical to several Spacelab Life Sciences (SLS-2) investigations.

  13. [Book review] Middle American Herpetology, by Jaime Villa, Larry David Wilson, and Jerry D. Johnson

    USGS Publications Warehouse

    Scott, N.J.

    1989-01-01

    Review of: Middle American Herpetology: a bibliographic checklist. By Jaime Villa, Larry David Wilson and Jerry D. Johnson. 1988. University of Missouri Press, Columbia, Missouri 65211. 132 p., 16 color plates, $35.00 (hardcover).

  14. "Handbook of biomedical optics", edited by David A. Boas, Constantinos Pitris, and Nimmi Ramanujam

    PubMed Central

    2012-01-01

    David A. Boas, Constantinos Pitris, and Nimmi Ramanujam, Eds.: Handbook of Biomedical Optics CRC Press, Taylor and Francis Group, Boca Raton, London, New York, 2011 ISBN: 978-1-4200-9036-9 (Hardback), 787 pages

  15. Dryden's David Bushman explains the capabilities of the Altus UAV to NASA Langley's Charles Hudgins

    NASA Image and Video Library

    2003-05-27

    David Bushman, unmanned aerial vehicle (UAV) mission manager in NASA Dryden's Airborne Science Program, explains the capabilities of the Altus UAV to Charles Hudgins of NASA Langley's Chemistry and Dynamics Branch.

  16. 78 FR 10608 - David Grant United States Air Force Medical Center Specialty Care Travel Reimbursement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-14

    ... of the Secretary David Grant United States Air Force Medical Center Specialty Care Travel... States Air Force Medical Center Specialty Care Travel Reimbursement Demonstration Project. This... MTF, and sustain readiness-related medical skills activities for the military providers....

  17. The association betweeen cancers and low level radiation: An evaluation of the epidemiological evidence at the Hanford Nuclear Weapons Facility

    SciTech Connect

    Britton, J. |

    1993-05-01

    Cancer has traditionally been linked to exposure to high doses of radiation, but there is considerable controversy regarding the carcinogenicity of low doses of ionizing radiation in humans. Over the past 30 years there have been 14 studies conducted on employees at the Hanford nuclear weapons facility to investigate the relationship between exposure to low doses of radiation and mortality due to cancer (1-14). Interest in this issue was originally stimulated by the Atomic Energy Commission (AEC) which was trying to determine whether the linear extrapolation of health effects from high to low dose exposure was accurate. If the risk has been underestimated, then the maximum permissible occupational radiation exposure in the United States had been set too high. Because the health risk associated with low level radiation are unclear and controversial it seems appropriate to review the studies relating to Hanford at this time.

  18. A multi-SNP association test for complex diseases incorporating an optimal P-value threshold algorithm in nuclear families.

    PubMed

    Wang, Yi-Ting; Sung, Pei-Yuan; Lin, Peng-Lin; Yu, Ya-Wen; Chung, Ren-Hua

    2015-05-15

    Genome-wide association studies (GWAS) have become a common approach to identifying single nucleotide polymorphisms (SNPs) associated with complex diseases. As complex diseases are caused by the joint effects of multiple genes, while the effect of individual gene or SNP is modest, a method considering the joint effects of multiple SNPs can be more powerful than testing individual SNPs. The multi-SNP analysis aims to test association based on a SNP set, usually defined based on biological knowledge such as gene or pathway, which may contain only a portion of SNPs with effects on the disease. Therefore, a challenge for the multi-SNP analysis is how to effectively select a subset of SNPs with promising association signals from the SNP set. We developed the Optimal P-value Threshold Pedigree Disequilibrium Test (OPTPDT). The OPTPDT uses general nuclear families. A variable p-value threshold algorithm is used to determine an optimal p-value threshold for selecting a subset of SNPs. A permutation procedure is used to assess the significance of the test. We used simulations to verify that the OPTPDT has correct type I error rates. Our power studies showed that the OPTPDT can be more powerful than the set-based test in PLINK, the multi-SNP FBAT test, and the p-value based test GATES. We applied the OPTPDT to a family-based autism GWAS dataset for gene-based association analysis and identified MACROD2-AS1 with genome-wide significance (p-value=2.5×10(-6)). Our simulation results suggested that the OPTPDT is a valid and powerful test. The OPTPDT will be helpful for gene-based or pathway association analysis. The method is ideal for the secondary analysis of existing GWAS datasets, which may identify a set of SNPs with joint effects on the disease.

  19. Latency-Associated Nuclear Antigen E3 Ubiquitin Ligase Activity Impacts Gammaherpesvirus-Driven Germinal Center B Cell Proliferation.

    PubMed

    Cerqueira, Sofia A; Tan, Min; Li, Shijun; Juillard, Franceline; McVey, Colin E; Kaye, Kenneth M; Simas, J Pedro

    2016-09-01

    Viruses have evolved mechanisms to hijack components of cellular E3 ubiquitin ligases, thus modulating the ubiquitination pathway. However, the biological relevance of such mechanisms for viral pathogenesis in vivo remains largely unknown. Here, we utilized murid herpesvirus 4 (MuHV-4) infection of mice as a model system to address the role of MuHV-4 latency-associated nuclear antigen (mLANA) E3 ligase activity in gammaherpesvirus latent infection. We show that specific mutations in the mLANA SOCS box (V199A, V199A/L202A, or P203A/P206A) disrupted mLANA's ability to recruit Elongin C and Cullin 5, thereby impairing the formation of the Elongin BC/Cullin 5/SOCS (EC5S(mLANA)) complex and mLANA's E3 ligase activity on host NF-κB and Myc. Although these mutations resulted in considerably reduced mLANA binding to viral terminal repeat DNA as assessed by electrophoretic mobility shift assay (EMSA), the mutations did not disrupt mLANA's ability to mediate episome persistence. In vivo, MuHV-4 recombinant viruses bearing these mLANA SOCS box mutations exhibited a deficit in latency amplification in germinal center (GC) B cells. These findings demonstrate that the E3 ligase activity of mLANA contributes to gammaherpesvirus-driven GC B cell proliferation. Hence, pharmacological inhibition of viral E3 ligase activity through targeting SOCS box motifs is a putative strategy to control gammaherpesvirus-driven lymphoproliferation and associated disease. The gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause lifelong persistent infection and play causative roles in several human malignancies. Colonization of B cells is crucial for virus persistence, and access to the B cell compartment is gained by virus-driven proliferation in germinal center (GC) B cells. Infection of B cells is predominantly latent, with the viral genome persisting as a multicopy episome and expressing only a small subset of viral genes. Here, we focused on

  20. Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1.

    PubMed

    Wang, Xing; He, Zhiheng; Xia, Tian; Li, Xiaofan; Liang, Deguang; Lin, Xianzhi; Wen, Hao; Lan, Ke

    2014-04-01

    Notch signaling has been implicated in the pathogenesis of Kaposi sarcoma. Kaposi sarcoma is an angioproliferative neoplasm that originates from Kaposi sarcoma-associated herpesvirus (KSHV) infection. Previously, we showed that the KSHV LANA protein can stabilize intracellular Notch in KSHV-infected tumor cells and promote cell proliferation. However, whether Notch signaling functions in pathologic angiogenesis of Kaposi sarcoma remains largely unknown. Hey1, an essential downstream effector of the Notch signaling pathway, has been demonstrated to play a fundamental role in vascular development. In the present study, we performed whole transcriptome, paired-end sequencing on three patient-matched clinical Kaposi sarcoma specimens and their corresponding adjacent stroma samples, with an average depth of 42 million reads per sample. Dll4, Hey1, and HeyL displayed significant upregulation in Kaposi sarcoma. Further verification based on immunohistochemistry analysis demonstrated that Hey1 was indeed highly expressed in Kaposi sarcoma lesions. Using the Matrigel plug assay, we showed that downregulation of Hey1 and γ-secretase inhibitor treatment caused dramatic reduction in the formation of new blood vessels in mice. Interestingly, LANA was responsible for the elevated level of Hey1 through inhibition of its degradation. Importantly, Hey1 stabilized by LANA promoted the neoplastic vasculature. Taken together, our data suggest that hijacking of the proangiogenic property of Hey1 by LANA is an important strategy utilized by KSHV to achieve pathologic angiogenesis and that Hey1 is a potential therapeutic target in Kaposi sarcoma.

  1. Testicular orphan nuclear receptor 4 is associated with the radio-sensitivity of prostate cancer.

    PubMed

    Yu, Shicheng; Wang, Mingchao; Ding, Xianfan; Xia, Liqun; Chen, Bide; Chen, Yicheng; Zhang, Zhigen; Niu, Yuanjie; Li, Gonghui; Chang, Chawnshang

    2015-10-01

    It is well known that a significant number of prostate cancers (PCa) showed different extents of radio-resistance and the tumor may recur after treatment. Recent studies demonstrated that Testicular orphan nuclear receptor 4 (TR4) could play a critical role in anti-oxidative stress responses and might modulate the DNA damage repair. The objective of this study is to investigate the role of TR4 in the radiotherapy for PCa. The TR4 expression in tissue samples from PCa patients treated with brachytherapy was measured by immunohistochemistry (IHC). Cell survival test and colony formation assay were applied to test the radio-sensitivity of PCa cells with modulated TR4 gene expression upon irradiation. PCa patients with biochemical recurrence (BCR) after brachytherapy tend to have higher TR4 expression (80%, n = 30) as compared to those without BCR (36.67%, n = 30). Survival analysis demonstrated a significant higher BCR occurrence in patients with high level of TR4 expression (HR = 3.474, 95%CI 1.678-7.192, P = 0.0008). Multivariate analysis showed that the TR4 staining score on IHC was the only significant variable for predicting the PCa patients' clinical outcomes after radiotherapy (OR = 9.919, 95% CI 2.516-39.101, P = 0.001). Using cell survival test and colony forming assay, we found that the addition of functional TR4 in PC3 cells lead to elevated radio-resistance. In contrast, knocking-down TR4 in LNCaP cells resulted in increased radio-sensitivity. The γH2AX foci kinetic analysis suggested that knocking down TR4 might delay the PCa cell's DNA damage repair which would enhance the radio-sensitivity. TR4 could mediate the PCa cells' radio-sensitivity and might become a prognostic indicator for PCa patients received radiotherapy. This study provides a novel approach to manipulate radio-sensitivity of PCa cells, and may bring a promoted therapeutic outcome of radiotherapy to battle PCa in future. © 2015 Wiley Periodicals, Inc.

  2. Prolonged induced hypothermia in hemorrhagic shock is associated with decreased muscle metabolism: a nuclear magnetic resonance-based metabolomics study.

    PubMed

    Lusczek, Elizabeth R; Lexcen, Daniel R; Witowski, Nancy E; Determan, Charles; Mulier, Kristine E; Beilman, Greg

    2014-01-01

    Hemorrhagic shock is a leading cause of trauma-related death in war and is associated with significant alterations in metabolism. Using archived serum samples from a previous study, the purpose of this work was to identify metabolic changes associated with induced hypothermia in a porcine model of hemorrhagic shock. Twelve Yorkshire pigs underwent a standardized hemorrhagic shock and resuscitation protocol to simulate battlefield injury with prolonged evacuation to definitive care in cold environments. Animals were randomized to receive either hypothermic (33°C) or normothermic (39°C) limited resuscitation for 8 h, followed by standard resuscitation. Proton nuclear magnetic resonance spectroscopy was used to evaluate serum metabolites from these animals at intervals throughout the hypothermic resuscitation period. Animals in the hypothermic group had a significantly higher survival rate (P = 0.02) than normothermic animals. Using random forest analysis, a difference in metabolic response between hypothermic and normothermic animals was identified. Hypothermic resuscitation was characterized by decreased concentrations of several muscle-related metabolites including taurine, creatine, creatinine, and amino acids. This study suggests that a decrease in muscle metabolism as a result of induced hypothermia is associated with improved survival.

  3. No association between LRP5 gene polymorphisms and bone and obesity phenotypes in Chinese male-offspring nuclear families.

    PubMed

    Yu, Jin-bo; Ke, Yao-hua; He, Jin-wei; Zhang, Hao; Hu, Wei-wei; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Gu, Jie-mei; Fu, Wen-zhen; Gao, Gao; Yue, Hua; Xiao, Wen-jin; Zhang, Zhen-lin

    2010-11-01

    To investigate the effect of low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms on bone and obesity phenotypes in young Chinese men. A total of 1244 subjects from 411 Chinese nuclear families were genotyped by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique at the Q89R, N740N, and A1330V sites in the LRP5 gene. Bone mineral density (BMD) in the lumbar spine and the hip, total fat mass and total lean mass were measured using dual-energy X-ray absorptiometry. The association between LRP5 gene polymorphisms and peak BMD, body mass index (BMI), total fat mass, total lean mass and percentage of fat mass was assessed using a quantitative transmission disequilibrium test (QTDT). No significant within-family associations were found between genotypes or haplotypes of the LRP5 gene and peak BMD, BMI, total fat mass, total lean mass and percentage of fat mass. The 1000 permutations that were subsequently simulated were in agreement with these within-family association results. Our results suggest that common polymorphic variations of the LRP5 gene do not influence peak bone mass acquisition and obesity phenotypes in young Chinese men.

  4. Emotion reactivity and regulation are associated with psychological functioning following the 2011 earthquake, tsunami, and nuclear crisis in Japan.

    PubMed

    Cavanagh, Sarah R; Fitzgerald, Erin J; Urry, Heather L

    2014-04-01

    Frequent and successful use of cognitive reappraisal, an emotion regulation strategy that involves rethinking the meaning of an emotional event in order to change one's emotional response, has been linked in everyday life to positive outcomes such as higher well-being. Whether we should expect this association to be maintained in a strong, temporally and spatially close emotional context is an unexplored question that might have important implications for our understanding of emotion regulation and its relations to psychological functioning. In this study of members of the U. S. Embassy Tokyo community in the months following the March 2011 earthquake, tsunami, and nuclear crisis in Japan, self-reported use of cognitive reappraisal was not related to psychological functioning, but demonstrated success using cognitive reappraisal to decrease feelings of unpleasantness in response to disaster-related pictures on a performance-based task was associated with fewer symptoms of depression and posttraumatic stress. Moreover, emotional reactivity to these pictures was associated with greater symptomatology. These results suggest that situational intensity may be an important moderator of reappraisal and psychological functioning relationships.

  5. Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing▿

    PubMed Central

    Kwun, Hyun Jin; da Silva, Suzane Ramos; Shah, Ishita M.; Blake, Neil; Moore, Patrick S.; Chang, Yuan

    2007-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5′ or 3′ end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses. PMID:17522213

  6. Interaction domains and nuclear targeting signals in subunits of the U2 small nuclear ribonucleoprotein particle-associated splicing factor SF3a.

    PubMed

    Huang, Ching-Jung; Ferfoglia, Fabio; Raleff, Flore; Krämer, Angela

    2011-04-15

    Human splicing factor SF3a is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP) and its three subunits of 60, 66, and 120 kDa are essential for splicing in vitro and in vivo. The SF3a heterotrimer forms in the cytoplasm and enters the nucleus independently of the U2 snRNP. Here, we have analyzed domains required for in vitro interactions between the SF3a subunits. Our results indicate that the SF3a66-SF3a120 interaction is mediated by a 27-amino acid region in SF3a120 C-terminal to the second suppressor-of-white-apricot and prp21/spp91 domain and amino acids 108-210 of SF3a66. Neither of these sequences contains known structural motifs, suggesting that the interaction domains are novel. Moreover, an ∼100-amino acid region, including the SURP2 domain of SF3a120 but extending into neighboring regions, is sufficient for binding to SF3a60. Analysis of determinants for nuclear import of SF3a demonstrates that SF3a120 provides the major nuclear localization signal and SF3a60 contributes to nuclear import.

  7. Nuclear magnetic resonance lipoprotein abnormalities in newly-diagnosed type 2 diabetes and their association with preclinical carotid atherosclerosis.

    PubMed

    Amor, Antonio J; Catalan, Marta; Pérez, Antonio; Herreras, Zoe; Pinyol, Montserrat; Sala-Vila, Aleix; Cofán, Montserrat; Gilabert, Rosa; Ros, Emilio; Ortega, Emilio

    2016-04-01

    Atherogenic dyslipidemia is common in type 2 diabetes (T2DM) and predicts cardiovascular disease, but information on the association of its components with atherosclerosis is scarce. We aimed to assess differences in the lipoprotein profile in newly-diagnosed T2DM and matched control individuals and their associations with preclinical carotid atherosclerosis. In a case-control study, we evaluated lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy and determined carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) by B-mode ultrasonography. We assessed 96 T2DM patients (median age 63 years, 44% women, 19% smokers, 54% hypertension, 38% dyslipidemia) and 90 non-diabetic controls matched for age, sex, and cardiovascular risk factors. In T2DM VLDL-particles (mainly large and enriched in cholesterol and triglycerides) were increased, and large HDL-particles (enriched in triglycerides and depleted in cholesterol) were reduced (p < 0.05; all comparisons). Regarding associations with preclinical atherosclerosis, VLDL triglyceride content (odds ratio [OR], 8.975; 95% confidence interval [CI], 2.330-34.576), total number of VLDL particles (OR, 2.713; CI, 1.601-4.598) and VLDL size (OR, 2.044; CI, 1.320-3.166), and the ratio cholesterol/triglycerides in HDL (OR, 0.638; CI, 0.477-0.852) were associated with plaque burden (≥3 plaques) independently of confounders, including conventional lipid levels. NMR-assessed advanced lipoprotein profile identifies lipid abnormalities associated with newly-diagnosed T2DM and preclinical atherosclerosis that are not captured by the traditional lipid profile. At this early stage of diabetes, NMR lipoproteins could be useful to identify candidates for a more comprehensive cardiovascular risk prevention strategy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Inhibition of replication and transcription activator and latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus by morpholino oligomers.

    PubMed

    Zhang, Yan-Jin; Wang, Kai-Yu; Stein, David A; Patel, Deendayal; Watkins, Rheba; Moulton, Hong M; Iversen, Patrick L; Matson, David O

    2007-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma and primary effusion lymphoma (PEL). The KSHV replication and transcription activator (RTA) and latency-associated nuclear antigen (LANA) play key roles in activating KSHV lytic replication and maintaining KSHV latency, respectively. Phosphorodiamidate morpholino oligomers (PMO) are similar to short single-stranded DNA oligomers, but possess a modified backbone that confers highly specific binding and resistance to nucleases. In this study, RTA and LANA mRNA in PEL cells were targeted by antisense peptide-conjugated PMO (P-PMO) in an effort to suppress KSHV replication. Highly efficient P-PMO uptake by PEL cells was observed. Treatment of PEL cells with a RTA P-PMO (RP1) reduced RTA expression in a dose-dependent and sequence-specific manner, and also caused a significant decrease in several KSHV early and late gene products, including vIL-6, vIRF-1, and ORF-K8.1A. KSHV viral DNA levels were reduced both in cells and culture supernatants of RP1 P-PMO-treated cells, indicating that KSHV lytic replication was suppressed. Treatment of BCBL-1 cells with P-PMO against LANA resulted in a reduction of LANA expression. Cell viability assays detected no cytotoxicity from P-PMO alone, within the concentration range used for the experiments in this study. These results suggest that RP1 P-PMO can specifically block KSHV replication, and further study is warranted.

  9. Induction of Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen by the lytic transactivator RTA: a novel mechanism for establishment of latency.

    PubMed

    Lan, Ke; Kuppers, Daniel A; Verma, Subhash C; Sharma, Nikhil; Murakami, Masanao; Robertson, Erle S

    2005-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent contributing to development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman desease. Following primary infection, latency is typically established. However, the mechanism by which KSHV establishes latency is not understood. We have reported that the latency-associated nuclear antigen (LANA) can repress RTA (for replication and transcription activator) expression by down-regulating its promoter. In this study, we show that RTA is associated with the virion particle. We also show that RTA can activate the LANA promoter and induce LANA expression in transient reporter assays. Additionally, the transcription of RTA correlates with LANA expression in the early stages of de novo infection of KSHV, and induction of LANA transcription is responsive to induction of RTA with an inducible system. This induction in LANA transcription was dependent on recombination signal sequence binding protein Jkappa (RBP-Jkappa), as a RBP-Jkappa-deficient cell line was significantly delayed and inefficient in LANA transcription with expression of RTA. These studies suggest that RTA contributes to establishment of KSHV latency by activating LANA expression in the early stages of infection by utilizing the major effector of the Notch signaling pathway RBP-Jkappa. This describes a feedback mechanism by which LANA and RTA can regulate each other and is likely to be a key event in the establishment of KSHV latency.

  10. Induction of Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen by the Lytic Transactivator RTA: a Novel Mechanism for Establishment of Latency

    PubMed Central

    Lan, Ke; Kuppers, Daniel A.; Verma, Subhash C.; Sharma, Nikhil; Murakami, Masanao; Robertson, Erle S.

    2005-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent contributing to development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman desease. Following primary infection, latency is typically established. However, the mechanism by which KSHV establishes latency is not understood. We have reported that the latency-associated nuclear antigen (LANA) can repress RTA (for replication and transcription activator) expression by down-regulating its promoter. In this study, we show that RTA is associated with the virion particle. We also show that RTA can activate the LANA promoter and induce LANA expression in transient reporter assays. Additionally, the transcription of RTA correlates with LANA expression in the early stages of de novo infection of KSHV, and induction of LANA transcription is responsive to induction of RTA with an inducible system. This induction in LANA transcription was dependent on recombination signal sequence binding protein Jκ (RBP-Jκ), as a RBP-Jκ-deficient cell line was significantly delayed and inefficient in LANA transcription with expression of RTA. These studies suggest that RTA contributes to establishment of KSHV latency by activating LANA expression in the early stages of infection by utilizing the major effector of the Notch signaling pathway RBP-Jκ. This describes a feedback mechanism by which LANA and RTA can regulate each other and is likely to be a key event in the establishment of KSHV latency. PMID:15919901

  11. Deceptive single-locus taxonomy and phylogeography: Wolbachia-associated divergence in mitochondrial DNA is not reflected in morphology and nuclear markers in a butterfly species

    PubMed Central

    Kodandaramaiah, Ullasa; Simonsen, Thomas J; Bromilow, Sean; Wahlberg, Niklas; Sperling, Felix

    2013-01-01

    The satyrine butterfly Coenonympha tullia (Nymphalidae: Satyrinae) displays a deep split between two mitochondrial clades, one restricted to northern Alberta, Canada, and the other found throughout Alberta and across North America. We confirm this deep divide and test hypotheses explaining its phylogeographic structure. Neither genitalia morphology nor nuclear gene sequence supports cryptic species as an explanation, instead indicating differences between nuclear and mitochondrial genome histories. Sex-biased dispersal is unlikely to cause such mito-nuclear differences; however, selective sweeps by reproductive parasites could have led to this conflict. About half of the tested samples were infected by Wolbachia bacteria. Using multilocus strain typing for three Wolbachia genes, we show that the divergent mitochondrial clades are associated with two different Wolbachia strains, supporting the hypothesis that the mito-nuclear differences resulted from selection on the mitochondrial genome due to selective sweeps by Wolbachia strains. PMID:24455146

  12. Nuclear inclusions mimicking poly(A)-binding protein nuclear 1 inclusions in a case of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia with a novel mutation in the valosin-containing protein gene.

    PubMed

    Matsubara, Shiro; Shimizu, Toshio; Komori, Takashi; Mori-Yoshimura, Madoka; Minami, Narihiro; Hayashi, Yukiko K

    2016-07-01

    A middle-aged Japanese man presented with slowly progressive asymmetric weakness of legs and arm but had neither ptosis nor dysphagia. He had a family history of similar condition suggestive of autosomal dominant inheritance. A muscle biopsy showed mixture of neurogenic atrophy and myopathy with rimmed vacuoles. Furthermore we found intranuclear inclusions that had a fine structure mimicking that of inclusions reported in oculopharyngeal muscular dystrophy (OPMD). Immunohistochemical staining for polyadenylate-binding nuclear protein 1, which is identified within the nuclear inclusions of OPMD, demonstrated nuclear positivity in this case. However, OPMD was thought unlikely based on the clinical features and results of genetic analyses. Instead, a novel mutation in valosin-containing protein, c.376A>T (p.Ile126Phe), was revealed. A diagnosis of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia was made. This is the first report of polyadenylate-binding nuclear protein 1-positive nuclear inclusions in the muscle of this condition. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion.

    PubMed

    Cai, Bo-Lei; Li, Yan; Shen, Liang-Liang; Zhao, Jin-Long; Liu, Yuan; Wu, Jun-Zheng; Liu, Yan-Pu; Yu, Bo

    2016-01-01

    Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman's rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01)/clinical staging (r = -0.41, P<0.01)/tumor stage (r = -0.28, P = 0.02)/nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.

  14. Murine Gammaherpesvirus 68 Expressing Kaposi Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen (LANA) Reveals both Functional Conservation and Divergence in LANA Homologs.

    PubMed

    Gupta, Arundhati; Oldenburg, Darby G; Salinas, Eduardo; White, Douglas W; Forrest, J Craig

    2017-10-01

    Latency-associated nuclear antigen (LANA) is a multifunctional protein encoded by members of the Rhadinovirus genus of gammaherpesviruses. Studies using murine gammaherpesvirus 68 (MHV68) demonstrated that LANA is important for acute replication, latency establishment, and reactivation in vivo Despite structural similarities in their DNA-binding domains (DBDs), LANA homologs from Kaposi sarcoma-associated herpesvirus (KSHV) and MHV68 exhibit considerable sequence divergence. We sought to determine if KSHV and MHV68 LANA homologs are functionally interchangeable. We generated an MHV68 virus that encodes KSHV LANA (kLANA) in place of MHV68 LANA (mLANA) and evaluated the virus's capacity to replicate, establish and maintain latency, and reactivate. kLANA knock-in (KLKI) MHV68 was replication competent in vitro and in vivo but exhibited slower growth kinetics and lower titers than wild-type (WT) MHV68. Following inoculation of mice, KLKI MHV68 established and maintained latency in splenocytes and peritoneal cells but did not reactivate efficiently ex vivo kLANA repressed the MHV68 promoter for ORF50, the gene that encodes the major lytic transactivator protein RTA, while mLANA did not, suggesting a likely mechanism for the KLKI MHV68 phenotypes. Bypassing this repression by providing MHV68 RTA in trans rescued KLKI MHV68 replication in tissue culture and enabled detection of KLKI MHV68 reactivation ex vivo These data demonstrate that kLANA and mLANA are functionally interchangeable for establishment and maintenance of latency and suggest that repression of lytic replication by kLANA, as previously shown with KSHV, is a kLANA-specific function that is transferable to MHV68.IMPORTANCE Kaposi sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) are members of the Rhadinovirus genus of gammaherpesviruses. These viruses establish lifelong infections that place their respective human and murine hosts at risk for cancer. Latency-associated nuclear

  15. Nuclear Nonproliferation

    SciTech Connect

    Atkins-Duffin, C E

    2008-12-10

    With an explosion equivalent of about 20kT of TNT, the Trinity test was the first demonstration of a nuclear weapon. Conducted on July 16, 1945 in Alamogordo, NM this site is now a Registered National Historic Landmark. The concept and applicability of nuclear power was demonstrated on December 20, 1951 with the Experimental Breeder Reactor Number One (EBR-1) lit four light bulbs. This reactor is now a Registered National Historic Landmark, located near Arco, ID. From that moment forward it had been clearly demonstrated that nuclear energy has both peaceful and military applications and that the civilian and military fuel cycles can overlap. For the more than fifty years since the Atoms for Peace program, a key objective of nuclear policy has been to enable the wider peaceful use of nuclear energy while preventing the spread of nuclear weapons. Volumes have been written on the impact of these two actions on the world by advocates and critics; pundits and practioners; politicians and technologists. The nations of the world have woven together a delicate balance of treaties, agreements, frameworks and handshakes that are representative of the timeframe in which they were constructed and how they have evolved in time. Collectively these vehicles attempt to keep political will, nuclear materials and technology in check. This paper captures only the briefest abstract of the more significant aspects on the Nonproliferation Regime. Of particular relevance to this discussion is the special nonproliferation sensitivity associated with the uranium isotope separation and spent fuel reprocessing aspects of the nuclear fuel cycle.

  16. Association between shortage of energy supply and nuclear gene mutations leading to carcinomatous transformation.

    PubMed

    DU, Jianping

    2016-01-01

    Anaerobic bacteria use glycolysis, an oxygen-independent metabolic pathway, whereas energy metabolism in the evolved eukaryotic cell is performed via oxidative phosphorylation, with all eukaryotic cell activities depending upon high energy consumption. However, in cancer cells evolving from eukaryotic cells, the energy metabolism switches from oxidative phosphorylation to glycolysis. The shortage of energy supply induces cancer cells to acquire specific characteristics. Base pair renewal is the most energy-consuming process in the cell, and shortage of energy supply may lead to errors in this process; the more prominent the shortage in energy supply, the more errors are likely to occur in base pair renewal, resulting in gene mutations and expression of cancer cell characteristics. Thus, shortage of energy supply is associated with carcinomatous transformation.

  17. Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation.

    PubMed

    Intasqui, Paula; Camargo, Mariana; Del Giudice, Paula T; Spaine, Deborah M; Carvalho, Valdemir M; Cardozo, Karina H M; Cedenho, Agnaldo P; Bertolla, Ricardo P

    2013-09-01

    Sperm DNA fragmentation has been suggested as a marker for infertility diagnosis and prognosis. Hence, understanding its impact on male physiology and post-genomic pathways would be clinically important. We performed the proteomics and functional enrichment analyses of viable spermatozoa from ejaculates with low and high sperm DNA fragmentation to identify protein expression and pathways altered in association with sperm DNA fragmentation. Sperm DNA fragmentation using the Comet assay and the Komet 6.0.1 software was assessed in raw samples from 89 subjects from a human reproduction service. The Low and High sperm DNA fragmentation groups were formed according to the Olive Tail Moment variable. Spermatozoa proteins from these groups were pooled and analyzed by a shotgun proteomic approach (2D nanoUPLC-ESI-MS(E)). Differentially expressed proteins were used for a functional enrichment study. Two hundred and fifty-seven proteins were identified or quantified in sperm from the Low and High sperm DNA fragmentation groups. Of these, seventy-one proteins were exclusively or overexpressed in the Low group, whereas twenty-three proteins were exclusively or overexpressed in the High group. One hundred and sixty-three proteins were conserved between these groups. We also functionally related the differentially expressed proteins in viable spermatozoa from the groups. Processes such as triacylglycerol metabolism, energy production, protein folding, response to unfolded proteins, and cellular detoxification were found to be altered in these cells. Sperm DNA fragmentation is associated with differential protein expression in viable spermatozoa. These proteins may potentially be used as biomarkers for sperm DNA integrity.

  18. Nuclear Power: Outlook for New U.S. Reactors

    DTIC Science & Technology

    2007-03-09

    MD) 4Q 2007 Areva EPR 1 Nine Mile Point (NY) 1st half 2008 Areva EPR 1 Not specified 4Q 2008 Areva EPR 3 Dominion North Anna (VA) Nov. 2007 GE ESBWR...Secretary Samuel Bodman. 51 Lovell, David L., Wisconsin Legislative Council Staff , State Statutes Limiting the Construction of Nuclear Power Plants

  19. Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer.

    PubMed

    Zeng, Wen; Sun, Hanying; Meng, Fankai; Liu, Zeming; Xiong, Jing; Zhou, Sheng; Li, Fan; Hu, Jia; Hu, Zhiquan; Liu, Zheng

    2015-01-01

    Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa. Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens. Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020). Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.

  20. Fluxes of radiocaesium associated with suspended sediment in rivers impacted by the Fukushima Daiichi Nuclear Power Plant

    NASA Astrophysics Data System (ADS)

    Smith, Hugh; Blake, Will; Onda, Yuichi; Yoshimura, Kazuya; Taniguchi, Keisuke; Yamashiki, Yosuke; Matsuura, Yuki; Taylor, Alex

    2014-05-01

    The Fukushima Daiichi Nuclear Power Plant accident which followed the earthquake and tsunami on 11 March 2011 resulted in the release of Cs-134 and Cs-137 into the surrounding environment, where highly elevated levels are reported. There is considerable concern about the redistribution of these radioactive contaminants from the atmosphere to vegetation, soil and aquatic systems. Fluvial redistribution of radiocaesium may contaminate downstream areas that were subject to low fallout and deliver significant quantities of highly contaminated fine sediment to the coastal zone. This study reports on the magnitude of fluvial transfer of Cs-134 and Cs-137 through river networks located across the fallout region. Initially six nested river monitoring stations were established within the Abukuma River basin from June 2011. Subsequently, an additional 23 stations were established between October 2012 and January 2013, which included stations within the Abukuma basin as well as smaller coastal catchments north and south of the power plant. Combined, these 29 sites represent a globally-unique river monitoring network designed to quantify sediment-associated transfer of radiocaesium from headwaters to the Pacific Coast of Japan. The catchments range in area from 8 to 5,172 km2 and span a large range in spatially-averaged radiocaesium inventories. Flow and turbidity (converted to suspended sediment concentration) were measured at each station while bulk suspended sediment samples were collected at regular intervals using time-integrated samplers to allow measurement of Cs-134 and Cs-137 activity concentrations by gamma spectrometry. Preliminary monitoring data showed highly elevated but also highly variable fluxes of radiocaesium in rivers across the fallout region. High magnitude flows in response to typhoon events exported large quantities of radiocaesium. Rivers are an important and continuing source of radiocaesium input to the coastal environment and the Pacific Ocean in