WorldWideScience

Sample records for european nuclear regulators

  1. Risks, regulation responsibilities and costs in nuclear waste management: A preliminary survey in the European Community

    Science.gov (United States)

    Orlowski, S.

    The use of nuclear energy produces radioactive waste which may present risks of pollution for man and his environment. Their protection must be ensured by technical or institutional controls. The report examines the second, i.e., the administrative, legal and financial measures, dealing with the management of radioactive waste in existence or under consideration within the Member States of the European Community. The following aspects are studied: laws and regulations, authorities concerned, costs and financing of radioactive waste management, civil liability, national policies, international aspects of radioactive waste management.

  2. Restructuring nuclear regulations.

    OpenAIRE

    Mossman, Kenneth L

    2003-01-01

    Nuclear regulations are a subset of social regulations (laws to control activities that may negatively impact the environment, health, and safety) that concern control of ionizing radiation from radiation-producing equipment and from radioactive materials. The impressive safety record among nuclear technologies is due, in no small part, to the work of radiation safety professionals and to a protection system that has kept pace with the rapid technologic advancements in electric power generati...

  3. Nuclear regulation and safety

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed. (DLC)

  4. ENSAR, a Nuclear Science Project for European Research Area

    NARCIS (Netherlands)

    Turzó, Ketel; Lewitowicz, Marek; Harakeh, Muhsin N.

    2015-01-01

    During the period from September 2010 to December 2014, the European project European Nuclear Science and Applications Research (ENSAR) coordinated research activities of the Nuclear Physics community performing research in three major subfields: Nuclear Structure, Nuclear Astrophysics, and Nuclear

  5. The European Nuclear Education Network Association - ENEN

    Energy Technology Data Exchange (ETDEWEB)

    Gentile, D. [Institut des Sciences et Techniques Nucleaires, CEA - Centre de Saclay, Bat. 395, F-91191 Gif-sur-Yvette (France)

    2006-07-01

    The temporary network, established through the European 5. Framework Programme project ENEN, was given a more permanent character by the foundation of the European Nuclear Education Network Association, a non-profit-making association according to the French law of 1901, pursuing a pedagogic and scientific aim. Its main objective is the preservation and the further development of higher nuclear education and expertise. This objective is realized through the co-operation between the European universities, involved in education and research in the nuclear engineering field, the nuclear research centres and the nuclear industry. The membership of the ENEN Association now consists of 35 universities members and 6 research centres. The paper briefly describes the history and structure of the ENEN Association and elaborates on the objectives and activities of its five committees during its first two years of operation. Supported by the 5. and 6. Framework Programme of the European Community, the ENEN Association established the delivery of the European Master of Science in Nuclear Engineering certificate. In particular, education and training courses have been developed and offered to materialize the core curricula and optional fields of study in a European exchange structure. Pilot editions of those courses and try-outs of training programmes have been successfully organised with a satisfying interest, attendance and performance by the students and the support of nuclear industries and international organisations. The involvement of ENEN in the 6. EC Framework project EUROTRANS will further enlarge its field of activities into a realm of nuclear disciplines. The ENEN Association further contributes to the management of nuclear knowledge within the European Union as well as on a world-wide level, through contacts with its sister Network ANENT in Asia, and by its participation to activities of the World Nuclear University. (author)

  6. EUROPEAN HARMONIZATION OF CONSOLIDATED FINANCIAL STATEMENTS REGULATIONS?

    National Research Council Canada - National Science Library

    Cirstea Andreea; Baltariu Carmen-Alexandra

    2012-01-01

    ... No. 1606/2002 adopted by the European Parliament and European Council on the 19th of July 2002, which regulates the application of IAS/IFRS regarding the financial reporting of listed European companies...

  7. ALARA in European nuclear installations

    Energy Technology Data Exchange (ETDEWEB)

    Lefaure, C. [CEPN, Fontenay-Aux-Roses (France); Croft, J. [NRPB, Chilton, Didcot (United Kingdom); Pfeffer, W. [GRS, Koeln (Germany); Zeevaert, T. [SCK/CEN, Mol (Belgium)

    1995-03-01

    For over a decade the Commission of the European Community has sponsored research projects on the development and practical implementation of the Optimization principle, or as it is often referred to, ALARA. These projects have given rise to a series of successful international Optimization training courses and have provided a significant input to the periodic European Seminars on Optimization, the last one of which took place in April 1993. This paper reviews the approaches to Optimization that have development within Europe and describes the areas of work in the current project. The on-going CEC research project addresses the problem of ALARA and internal exposures, and tries to define procedures for ALARA implementation, taking account of the perception of the hazard as well as the levels of probability of exposure. The relationships between ALARA and work management, and ALARA and decommissioning of installations appear to be other fruitful research areas. Finally, this paper introduces some software for using ALARA decision aiding techniques and databases containing feed back experience developed in Europe.

  8. Essential infrastructure: national nuclear regulation.

    Science.gov (United States)

    Paperiello, Carl J

    2011-01-01

    In order for nuclear power to expand to many countries that do not currently have it, it will be essential for these countries to have laws, regulations, guidance and organizations that can license or permit nuclear power plants and support nuclear facilities, ensure compliance by inspection, and enforce nuclear regulations. The viability of nuclear power worldwide depends on an extremely high level of safety everywhere, and compliance with a number of international treaties is required before supplier nations will provide the material, both hardware and software, to build and operate nuclear power plants. While infrastructure support can be obtained from the IAEA and other countries, an essential core of expertise must exist in the country seeking to establish domestic nuclear power generation. While some reliance can be placed on the safety reviews of standard reactor designs by the nuclear regulators in supplier nations, the certification of fuel design, the quality of instruments, and the matching of a new reactor to a proposed site in the importing nation will require site-specific reviews. National arrangements are also needed for emergency preparedness, environmental protection, fuel transportation and the storage, transportation and disposal of radioactive waste. If foreign contractors and consultants are engaged to perform much of the technical work for the regulatory body(s) that has to be performed by the importing nation, that nation must have a core cadre of technically knowledgeable regulators and an organization to provide management and oversight of the contractors and consultants. Consistency in national nuclear regulations, the deployment of standardized nuclear power plant designs and standardized supporting material infrastructure can promote the safe and secure worldwide growth in nuclear power. Copyright © 2010 Health Physics Society

  9. Nuclear legislation in the European Union; Legislacion nuclear en la Union Europea

    Energy Technology Data Exchange (ETDEWEB)

    Dovale, I.

    2009-07-01

    European Nuclear Legislation, developed under the Euratom Treaty, has evolved in accordance with established priorities and the interpretation of the Treaty on the legislative competence of the Community, and prevailing in particular rules on radiological protection and prevention against the risks of proliferation. The approval, in this year 2009, of a Directive on Nuclear Safety, is an important step in the harmonization of legislation on matters that have not been subject to common regulation, as nuclear safety, and it could have its continuation in a future Directive on the safety, and it could have its continuation in a future. Directive on the safety radioactive waste management. As for nuclear safeguards, a reform in the safeguards regimes in both European and international field has been promoted in order to implement an integrated safeguards system, whose implementation is expected to finalise in January 2010. (Author)

  10. Nuclear phosphoinositide regulation of chromatin.

    Science.gov (United States)

    Hamann, Bree L; Blind, Raymond D

    2018-01-01

    Phospholipid signaling has clear connections to a wide array of cellular processes, particularly in gene expression and in controlling the chromatin biology of cells. However, most of the work elucidating how phospholipid signaling pathways contribute to cellular physiology have studied cytoplasmic membranes, while relatively little attention has been paid to the role of phospholipid signaling in the nucleus. Recent work from several labs has shown that nuclear phospholipid signaling can have important roles that are specific to this cellular compartment. This review focuses on the nuclear phospholipid functions and the activities of phospholipid signaling enzymes that regulate metazoan chromatin and gene expression. In particular, we highlight the roles that nuclear phosphoinositides play in several nuclear-driven physiological processes, such as differentiation, proliferation, and gene expression. Taken together, the recent discovery of several specifically nuclear phospholipid functions could have dramatic impact on our understanding of the fundamental mechanisms that enable tight control of cellular physiology. © 2017 Wiley Periodicals, Inc.

  11. Sumoylation regulates nuclear localization of repressor DREAM.

    Science.gov (United States)

    Palczewska, Malgorzata; Casafont, Iñigo; Ghimire, Kedar; Rojas, Ana M; Valencia, Alfonso; Lafarga, Miguel; Mellström, Britt; Naranjo, Jose R

    2011-05-01

    DREAM is a Ca(2+)-binding protein with specific functions in different cell compartments. In the nucleus, DREAM acts as a transcriptional repressor, although the mechanism that controls its nuclear localization is unknown. Yeast two-hybrid assay revealed the interaction between DREAM and the SUMO-conjugating enzyme Ubc9 and bioinformatic analysis identified four sumoylation-susceptible sites in the DREAM sequence. Single K-to-R mutations at positions K26 and K90 prevented in vitro sumoylation of recombinant DREAM. DREAM sumoylation mutants retained the ability to bind to the DRE sequence but showed reduced nuclear localization and failed to regulate DRE-dependent transcription. In PC12 cells, sumoylated DREAM is present exclusively in the nucleus and neuronal differentiation induced nuclear accumulation of sumoylated DREAM. In fully differentiated trigeminal neurons, DREAM and SUMO-1 colocalized in nuclear domains associated with transcription. Our results show that sumoylation regulates the nuclear localization of DREAM in differentiated neurons. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. 2010 Elsevier B.V. All rights reserved.

  12. Inside CERN European Organization for Nuclear Research

    CERN Document Server

    Pol, Andri; Heuer, Rolf

    2013-01-01

    For most people locations that hold a particular importance for the development of our society and for the advancement of science and technology remain hidden from view. CERN, the European Organization for Nuclear Research, is best known for its giant particle accelerator. Here researchers take part in a diverse array of fundamental physical research, in the pursuit of knowledge that will perhaps one dayrevolutionize our understanding of the universe and life on our planet. The Swiss photographer Andri Pol mixed with this multicultural community of researchers and followed their work over an extended period of time. In doing so he created a unique portrait of this fascinating “underworld.” The cutting-edge research is given a human face and the pictures allow us to perceive how in this world of the tiniest particles the biggest connections are searched for. With an essay by Peter Stamm.

  13. Nuclear data for fusion technology - the European approach

    Science.gov (United States)

    Fischer, Ulrich; Avrigeanu, Marilena; Avrigeanu, Vlad; Cabellos, Oscar; Dzysiuk, Natalia; Koning, Arjan; Klix, Axel; Konobeev, Alexander; Kodeli, Ivo; Leeb, Helmut; Leichtle, Dieter; Nunnenmann, Elena; Packer, Lee; Rochman, Dimitri; Pereslavtsev, Pavel; Sauvan, Patrick; Trkov, Andrej

    2017-09-01

    The European approach for the development of nuclear data for fusion technology applications is presented. Related R&D activities are conducted by the Consortium on Nuclear Data Development and Analysis for Fusion to satisfy the nuclear data needs of the major projects including ITER, the Early Neutron Source (ENS) and DEMO. Recent achievements are presented in the area of nuclear data evaluations, benchmarking and validation, nuclear model improvements, and uncertainty assessments.

  14. Nuclear data for fusion technology – the European approach

    Directory of Open Access Journals (Sweden)

    Fischer Ulrich

    2017-01-01

    Full Text Available The European approach for the development of nuclear data for fusion technology applications is presented. Related R&D activities are conducted by the Consortium on Nuclear Data Development and Analysis for Fusion to satisfy the nuclear data needs of the major projects including ITER, the Early Neutron Source (ENS and DEMO. Recent achievements are presented in the area of nuclear data evaluations, benchmarking and validation, nuclear model improvements, and uncertainty assessments.

  15. Comparison of some European regulations

    Energy Technology Data Exchange (ETDEWEB)

    Argyriadis, K. [Germanisher Lloyd, Hamburg (Germany)

    1996-09-01

    Fatigue calculations are an essential part in certification of a wind turbine. Manufacturers have to fulfill recommendations of several different regulations throughout Europe with the result that the design has often to be altered to satisfy them. In general three national (D/GL, NL, DK), and two international (GL, IEC) regulations are in use, with the IEC standard getting more importance with wind energy deploying to more in regions with no yet clearly defined national standards (India, Spain). The Germanischer Lloyd made calculations for wind turbines they are certifying and in one case we compared the resulting damages for different regulations and classes on a 600 kW, three bladed, stall regulated wind turbine. (EG) 18 refs.

  16. The European Nuclear Science network touches base at CERN

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    ENSAR (European Nuclear Science and Applications Research) is an EU-supported project, which aims at fostering cooperation within the European low-energy nuclear physics community through the active sharing of expertise and best practices. The project also includes a transnational access programme to allow a large community of users to access the participating facilities, which include CERN’s ISOLDE. In the last week of April, CERN hosted the General Assembly and Programme Coordination Committee meetings, about 18 months after the project’s kick-off.   Participants in the ENSAR project. ENSAR involves 30 partner institutes, which include the seven large nuclear physics facilities in Europe. A large part of the European nuclear physics community is represented in ENSAR, in particular scientists who are performing research related to nuclear structure, nuclear astrophysics and applications of nuclear science. In 2010, the project was awarded 8 million euros from the Europe...

  17. European single-hull regulation in force

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Michael

    2004-07-01

    The European Union (EU)has decided that from 21 October 2003 no single-hull tanker carrying heavy grades of oil will be permitted to enter or leave ports or offshore installations or anchor in areas under the jurisdiction of the EU member states. Some of the provisions of the EU regulation will not be in force until 2010. The article looks back on what has led up to to the current regulations, beginning with the Titanic disaster of 1914.

  18. EUROPEAN ACCOUNTING REGULATION - HISTORY AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    Mariana Farcas

    2014-07-01

    Full Text Available The first directive regarding the financial reporting at the level of European Union is published in 1978 (The Fourth Directive and whereas its content does not refer to the group companies, this directive was supplemented by another directive (The Seventh Directive published in 1983. The two directives regulate in parallel the issues concerning the preparing of the annual financial statements of individual companies, respectively of the group companies. Since 2008 have begun to take shape the point of views regarding the need of the development and publication of some regulations to simplify and to reduce the administrative burdens of the companies, including on the issue of financial reporting. The steps in the direction of simplification of the regulation in accounting area have resulted in June 2013 in The 34th Directive regarding the annual financial statements, the consolidated financial statements and the related reports of certain types of companies. As a member of the European Union, Romania must take into account the implementation of the European legislation in all areas, including in the field of accounting. In this respect, The Fourth Directive regarding the annual accounts of certain types of companies and The Seventh Directive regarding the consolidated accounts have been transposed into Romanian legislation since 2006 through OMFP 1752/2005 when the Romanian accounting regulations have become in accordance to the European directives and not only harmonized with these, and OMFP 3055/2009 brings additional information concerning the rules relating to the consolidation of accounts.

  19. EUROPEAN HARMONIZATION OF CONSOLIDATED FINANCIAL STATEMENTS REGULATIONS?

    Directory of Open Access Journals (Sweden)

    Cirstea Andreea

    2012-07-01

    Full Text Available The purpose of this paper is to analyze the degree of formal accounting harmonization within the European Union with respect to the EC Regulation No. 1606/2002 adopted by the European Parliament and European Council on the 19th of July 2002, which regulates the application of IAS/IFRS regarding the financial reporting of listed European companies. The conclusions of the paper were drawn after the completion of a thorough analysis performed by using correlation and/ or association coefficients, namely: the Jaccard’s Correlation Coefficients, Rogers and Tanimoto Coefficient, Lance and Williams Coefficient and Binary Euclidian Distance Coefficient. The results lead us to conclude that although our first hypothesis is verified, the degree of harmonization between the accounting systems of EU Member States could be truly quantified only through an analysis of the material accounting harmonization, more precisely by analyzing the way the companies put into practice the requirements imposed through the EC Regulation No. 1606/2002.

  20. Fascin regulates nuclear actin during Drosophila oogenesis.

    Science.gov (United States)

    Kelpsch, Daniel J; Groen, Christopher M; Fagan, Tiffany N; Sudhir, Sweta; Tootle, Tina L

    2016-10-01

    Drosophila oogenesis provides a developmental system with which to study nuclear actin. During Stages 5-9, nuclear actin levels are high in the oocyte and exhibit variation within the nurse cells. Cofilin and Profilin, which regulate the nuclear import and export of actin, also localize to the nuclei. Expression of GFP-tagged Actin results in nuclear actin rod formation. These findings indicate that nuclear actin must be tightly regulated during oogenesis. One factor mediating this regulation is Fascin. Overexpression of Fascin enhances nuclear GFP-Actin rod formation, and Fascin colocalizes with the rods. Loss of Fascin reduces, whereas overexpression of Fascin increases, the frequency of nurse cells with high levels of nuclear actin, but neither alters the overall nuclear level of actin within the ovary. These data suggest that Fascin regulates the ability of specific cells to accumulate nuclear actin. Evidence indicates that Fascin positively regulates nuclear actin through Cofilin. Loss of Fascin results in decreased nuclear Cofilin. In addition, Fascin and Cofilin genetically interact, as double heterozygotes exhibit a reduction in the number of nurse cells with high nuclear actin levels. These findings are likely applicable beyond Drosophila follicle development, as the localization and functions of Fascin and the mechanisms regulating nuclear actin are widely conserved. © 2016 Kelpsch et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. Nuclear power. A key contributor to a decarbonised European Union

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-12-15

    The European energy sector is currently facing a new set of challenges in the light of the COP21 Paris agreement, the Energy Union initiative and new market design projections. Nuclear energy sector understands the post COP21 constellation as a unique opportunity for all low carbon technologies which will be basic for transition towards COP21 commitments. A new policy outlook for Europe is needed in order to provide low carbon capacity, lead to the modernisation of technical processes and contribute to the prosperity of Europeans. The benefits of nuclear are highlighted for a low carbon future and for the security of supply and recommend actions for supporting new investments.

  2. CERN - European Organization for Nuclear Research

    CERN Multimedia

    Holmes, Addison

    2004-01-01

    Why do we have mass? What is the universe made of and how old is it? Why do two particles arat seem to instantaneously react to each other? Fifty years ago, these and many others questions made physics the field for any mathermatical inquiring mind and it was the US that led the field. For this reason, amongs others, 11 European countries initiated a project, under the auspices of UNESCO, to assemble their collective resources and minds to explore the universe at the sub-atommic level (2 pages)

  3. European Clearinghouse for Nuclear Power Plants Operational Experience Feedback

    Energy Technology Data Exchange (ETDEWEB)

    Martin Ramos, M.; Noel, M.

    2010-07-01

    In the European Union, in order to support the Community activities on operational experience, a centralized regional network on nuclear power plants operational experience feedback (European Clearinghouse on Operational Experience Feedback for Nuclear Power Plants) was established in 2008 at the EC JRC-IE, Petten (The Netherlands) on request of nuclear Safety Authorities of several Member States. Its main goal is to improve the communication and information sharing on OEF, to promote regional collaboration on analyses of operational experience and dissemination of the lessons learned. The enlarged EU Clearinghouse was launched in April 2010, and it is currently gathering the Regulatory Authorities of Finland, Hungary, Lithuania, the Netherlands, Romania, Slovenia, Switzerland, Bulgaria, Czec Republic, France, Germany, Slovak Republic, and Spain (these last six countries as observers). The OECD Nuclear Energy Agency, the IAEA, the EC Directorates General of the JRC and ENER are also part of the network. Recently, collaboration between some European Technical Support Organizations (such IRSN and GRS) and the EU Clearinghouse has been initiated. This paper explains in detail the objectives and organization of the EU Clearinghouse, as well as the most relevant activities carried out, like research work in trend analysis of events ocurred in NPP, topical reports on particular events, dissemination of the results, quarterly reports on events reported publicly and operational experience support to the members of the EU Clearinghouse. (Author)

  4. 76 FR 81359 - European Larch Canker; Expansion of Regulated Areas

    Science.gov (United States)

    2011-12-28

    ... Management and Budget has waived its review under Executive Order 12866. List of Subjects in 7 CFR Part 301... Animal and Plant Health Inspection Service 7 CFR Part 301 European Larch Canker; Expansion of Regulated... domestic quarantine regulations by expanding the regulated area for European larch canker to include...

  5. Nuclear Energy and European Union; Energia nuclear y la Union Europea

    Energy Technology Data Exchange (ETDEWEB)

    Picamal, B.

    2010-07-01

    The interest shown by the European Institutions in the energy debates, in which the nuclear energy is included as a key component within the energy mix, is obvious. Climate change and energy supply have pushed some countries to publicly express their interest for developing the nuclear energy. These positions are however in contradiction with some others within the European Union which are a lot more critical towards this type of energy and where face-out policies still prevail. Despite the fact that the use of the nuclear energy will remain within the competence of each Member State, the European Union will continue to play a prominent role in the development of an energy strategy based on a low carbon economy. (Author)

  6. VI European Summer School on Experimental Nuclear Astrophysics

    Science.gov (United States)

    The European Summer School on Experimental Nuclear Astrophysics has reached the sixth edition, marking the tenth year's anniversary. The spirit of the school is to provide a very important occasion for a deep education of young researchers about the main topics of experimental nuclear astrophysics. Moreover, it should be regarded as a forum for the discussion of the last-decade research activity. Lectures are focused on various aspects of primordial and stellar nucleosynthesis, including novel experimental approaches and detectors, indirect methods and radioactive ion beams. Moreover, in order to give a wide educational offer, some lectures cover complementary subjects of nuclear astrophysics such as gamma ray astronomy, neutron-induced reactions, short-lived radionuclides, weak interaction and cutting-edge facilities used to investigate nuclear reactions of interest for astrophysics. Large room is also given to young researcher oral contributions. Traditionally, particular attention is devoted to the participation of students from less-favoured countries, especially from the southern coast of the Mediterranean Sea. The school is organised by the Catania Nuclear Astrophysics research group with the collaboration of Dipartimento di Fisica e Astromomia - Università di Catania and Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare.

  7. 10 CFR 1.43 - Office of Nuclear Reactor Regulation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Office of Nuclear Reactor Regulation. 1.43 Section 1.43... Program Offices § 1.43 Office of Nuclear Reactor Regulation. The Office of Nuclear Reactor Regulation— (a... health and safety, the environment, or the safeguarding of nuclear reactor facilities; (c) Assesses and...

  8. European Sustainable Construction Regulation : Homogeneity and Attention

    NARCIS (Netherlands)

    Van der Heijden, J.; Van Bueren, E.M.

    2011-01-01

    Understanding the negative impact of the construction industry and the built environment on the ecological environment, the European Commission (EC) aims to harmonise and improve sustainable construction regulatory frameworks in Member States of the European Union. This paper discusses the topics of

  9. The Activities of the European Consortium on Nuclear Data Development and Analysis for Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, U., E-mail: ulrich.fischer@kit.edu [Karlsruhe Institute of Technology, Institute for Neutron Physic and Reactor Technology, 76344 Eggenstein-Leopoldshafen (Germany); Avrigeanu, M.; Avrigeanu, V. [Horia Hulubei National Institute of Physics and Nuclear Engineering (IFIN-HH), RO-077125 Magurele (Romania); Cabellos, O. [Departamento de Ingenieria Nuclear, Universidad Politecnica de Madrid, 28006 Madrid (Spain); Kodeli, I. [Jozef Stefan Institute (JSI), Jamova 39, 1000 Ljubljana (Slovenia); Koning, A. [Nuclear Research and Consultancy Group (NRG), Westerduinweg 3, 1755 LE Petten (Netherlands); Konobeyev, A.Yu. [Karlsruhe Institute of Technology, Institute for Neutron Physic and Reactor Technology, 76344 Eggenstein-Leopoldshafen (Germany); Leeb, H. [Technische Universitaet Wien, Atominstitut, Wiedner Hauptstrasse 8–10, 1040 Wien (Austria); Rochman, D. [Nuclear Research and Consultancy Group (NRG), Westerduinweg 3, 1755 LE Petten (Netherlands); Pereslavtsev, P. [Karlsruhe Institute of Technology, Institute for Neutron Physic and Reactor Technology, 76344 Eggenstein-Leopoldshafen (Germany); Sauvan, P. [Universidad Nacional de Educacion a Distancia, C. Juan del Rosal, 12, 28040 Madrid (Spain); Sublet, J.-C. [Euratom/CCFE Fusion Association, Culham Science Centre, OX14 3DB (United Kingdom); Trkov, A. [Jozef Stefan Institute (JSI), Jamova 39, 1000 Ljubljana (Slovenia); Dupont, E. [OECD Nuclear Energy Agency, Paris (France); Leichtle, D.; Izquierdo, J. [Fusion for Energy, Barcelona (Spain)

    2014-06-15

    This paper presents an overview of the activities of the European Consortium on Nuclear Data Development and Analysis for Fusion. The Consortium combines available European expertise to provide services for the generation, maintenance, and validation of nuclear data evaluations and data files relevant for ITER, IFMIF and DEMO, as well as codes and software tools required for related nuclear calculations.

  10. Annual congress of the European Association of Nuclear Medicine. EANM'14. Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-10-15

    The proceedings of the annual congress of the European Association of Nuclear Medicine EANM'14 contain abstracts on the following issues: nuclear cardiology practices, PET in lymphoma, advances in nuclear cardiology, dosimetry for intra-arterial treatment in the liver, pediatric nuclear medicine, therapeutic nuclear medicine, SPECT/CT, prostate cancer, extended competencies for nuclear medicine technologists, neurosciences - neurodegeneration and neuroinflammation, radionuclide therapy and dosimetry - preclinical studies, physics and instrumentation, clinical molecular imaging, conventional and specialized nuclear medicine.

  11. Brain nuclear receptors and body weight regulation.

    Science.gov (United States)

    Xu, Yong; O'Malley, Bert W; Elmquist, Joel K

    2017-04-03

    Neural pathways, especially those in the hypothalamus, integrate multiple nutritional, hormonal, and neural signals, resulting in the coordinated control of body weight balance and glucose homeostasis. Nuclear receptors (NRs) sense changing levels of nutrients and hormones, and therefore play essential roles in the regulation of energy homeostasis. Understanding the role and the underlying mechanisms of NRs in the context of energy balance control may facilitate the identification of novel targets to treat obesity. Notably, NRs are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of energy balance, including feeding, energy expenditure and physical activity. In this Review we summarize some of the recent literature regarding effects of brain NRs on body weight regulation and discuss mechanisms underlying these effects.

  12. Regulation of Genetically Modified Organisms in the European Union

    NARCIS (Netherlands)

    Grossman, M.R.; Bryan Endres, A.

    2000-01-01

    To be successful, laws that regulate genetically modified organisms (GMOs) must help society decide rationally when to pause and when to proceed in adopting new biotechnological developments. In the context of European Union (EU) institutions and lawmaking procedures, this article examines European

  13. The view at nuclear renaissance via actual European and Slovak approach to nuclear education

    Energy Technology Data Exchange (ETDEWEB)

    Slugen, Vladimir [Slovak University of Technology, FEI STU, Ilkovicova 3, 812 19 Bratislava (Slovakia)

    2010-07-01

    In the last decade, preservation and optimal nuclear knowledge management are becoming a rising challenge worldwide. Many papers and experts talks at different conferences stressed attention on stagnating or decreasing expertise connecting to decreased numbers of graduates, professors or research workers. Several networks were created in the Europe in frame of the 5. and 6. EURATOM Framework Programme accented international collaboration in training and education physics (EUPEN, STEPS) or in nuclear power engineering (ENEN, NEPTUNO). In the Central-European region, there exists a very extensive and also effective international collaboration in nuclear industry and education. Similarly good situation is also among universities and technical high schools in this area. Actually, the Slovak University of Technology in Bratislava has established contacts with many universities abroad in the area of utilization of research and training reactors. One of good examples of international collaboration is ENEN - European Nuclear Education Network Association which resulted in a formation of 'Eugene Wigner Training Courses on Reactor Physics Experiments' running in the last 2 years as a mutual effort of the Budapest University of Technology and Economics (Budapest, Hungary), Czech Technical University (Prague, Czech Republic), University of Technology (Vienna, Austria), and Slovak University of Technology in Bratislava (Bratislava, Slovakia). In total 69 participants from different European countries as Austria, Belgium, Bulgaria, Czech Republic, Finland, Italy, Israel, Romania, Slovakia, Slovenia, Sweden and Switzerland took part at these international training courses so far. In the frame of these courses, students of nuclear engineering vivisited three different experimental facilities located at the course organisers' institutes and carried out experimental laboratory practices. The preservation of nuclear knowledge is possible only via effective use of all

  14. Handbook on interdisciplinary use of European nuclear physics facilities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    This handbook is intended to collect together, in an accessible way, the most pertinent information which might be needed by anyone contemplating the use of nuclear physics accelerators for research in other disciplines, or for industrial, biomedical, solid-state or other applications. Information for the publication was supplied by each laboratory represented here, and this was edited and supplemented where it was thought necessary, by additional material, often derived from the facilities' web-sites. The reader will find for each facility a technical description concerning the accelerator itself and its experimental equipment, followed by a 'what can be made there' section. 'at a glance' page contains a summary of contact names and addresses, transport, access and accommodation offered that will be of a great use for prospective user. 26 facilities in 12 European countries (Belgium, Finland, France, Germany, Italy, Norway, Poland, Portugal, Spain, Sweden, Switzerland and The Netherlands) are presented.

  15. 76 FR 52543 - European Larch Canker; Expansion of Regulated Areas

    Science.gov (United States)

    2011-08-23

    ... Areas AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Interim rule and request for comments. SUMMARY: We are amending the domestic quarantine regulations to expand the regulated area for European larch canker to include additional areas in Maine. We are also correcting some misidentifications...

  16. Nuclear weapons and European interests : Discussions in the Assembly of the Western European Union, 1955–1975

    NARCIS (Netherlands)

    Megens, C.M

    2011-01-01

    In the 1950s and 1960s the Defence Committee of the Western European Union (WEU) Assembly submitted a series of conspicuous reports on nuclear control issues, culminating in a plea for an Atlantic nuclear force. The article analyses the reports and discussions in the Assembly in the field of defence

  17. Developing the European Center of Competence on VVER-Type Nuclear Power Reactors

    Science.gov (United States)

    Geraskin, Nikolay; Pironkov, Lyubomir; Kulikov, Evgeny; Glebov, Vasily

    2017-01-01

    This paper presents the results of the European educational projects CORONA and CORONA-II which are dedicated to preserving and further developing nuclear knowledge and competencies in the area of VVER-type nuclear power reactors technologies (Water-Water Energetic Reactor, WWER or VVER). The development of the European Center of Competence for…

  18. Improvement and rationalization of nuclear energy laws and regulations

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chum; Kim, Hak Man; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

    2002-03-15

    Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.

  19. Improvement and rationalization of nuclear energy laws and regulations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mo Sung; Chung, Gum Chun; Kim, Hak Man; Oh, Ho Chul [Cheongju Univ., Cheongju (Korea, Republic of)

    2001-03-15

    Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.

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

    Science.gov (United States)

    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. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  1. Public opinion poll on safety and regulations of nuclear energy

    Energy Technology Data Exchange (ETDEWEB)

    Park, M. I.; Park, B. I.; Lee, S. M. [Gallup Korea, Seoul (Korea, Republic of)

    2004-02-15

    The purpose of this poll is not only to research understanding on safety and regulations of nuclear energy and to compare the result by time series followed 2003 to 2002 years, also to establish the public relations strategies and to offer information for developing long-term policies. The contents of the study are on the general perception, safety, management of nuclear power station, regulations and surroundings about nuclear energy.

  2. The UAE. Lessons learned from a new nuclear regulator

    Energy Technology Data Exchange (ETDEWEB)

    Kraev, Kamen [NucNet, Brussels (Belgium)

    2015-12-15

    The United Arab Emirates (UAE) is building four South Korean APR-1400 reactors at the Barakah nuclear site. The first is scheduled to enter into commercial operation in 2017. Christer Viktorsson, Director General of the United Arabic Emirate's(UAE) Federal Office for Nuclear Regulation, talks to NucNet about the challenges of establishing a nuclear regulatory body from scratch in a country where nuclear stations have never been built before.

  3. Laboratory experiments on the regulation of European network industries

    NARCIS (Netherlands)

    Henze, B.

    2016-01-01

    The main objective of this thesis is to use economic laboratory experiments in order to evaluate the performance of regulatory schemes and market designs in addressing challenges encountered in the regulation of European network industries. Chapter 2 assesses whether regulatory holidays and Long

  4. Impact of regulation and supervision on European banks’ stability

    Directory of Open Access Journals (Sweden)

    Faten Ben Bouheni

    2014-03-01

    Full Text Available This article applies the Generalized Method of Moments technique for dynamic panels, using bank-level data for the selected European countries over the period 2005 to 2011, to investigate the impact of regulation and supervision on risk taking. Three conclusions are reached. First, in France, Germany and UK, restriction on bank activities boosts banking stability. However, supervisors’ power and capital adequacy encourage risk taking. Second, in Italy, Greece and Spain, we find that with more supervisors’ power, largest banks tend to take greater risks and strengthening regulation and supervision weakens the bank’s stability. However, the capital requirements decrease the risk taking. Third, strengthening regulatory and supervisory framework, and compliance with Basel principles enhance financial stability in Europe. These different results between European countries show that the application of regulation and supervision depends on the monitoring mode and the rhythm of application of regulatory policies

  5. THE EUROPEAN MODEL OF STATE REGULATION OF TOURISM ACTIVITIES

    Directory of Open Access Journals (Sweden)

    О. Davydova

    2013-11-01

    Full Text Available In the article the existing model of state regulation of the development of tourism. Expediency of the European model of state regulation of tourism development in Ukraine. It is noted that the European model of state regulation of tourism activities based on the coordination of marketing activities and the development of cooperation between the public and private sectors. The basic forms of public-private partnerships and the advantages of using cluster model of development of tourism, namely, contracts, production sharing agreement, lease, joint venture. Promising areas of application of the PPP identified the transport sector, housing and utilities, energy and tourism sector. The features of cluster formations in the country and the prospects for tourism clusters.

  6. Ethical Principles in European regulation of biotechnology - possibilities and pitfalls

    DEFF Research Database (Denmark)

    Faber, Berit Andersen; Nielsen, Linda

    2002-01-01

    The purpose of this report is to discribe, analyse and assess the varying methods of operationalising ethical principles within European regulation of biotechnology, with the inclusion of proposals for different tools and models for use in future regulation. The aim of the report is first...... and foremost to serve as a practical resource for use in evolving regulation, political support, and democratic and debating activities in different domains in response to rapid advances in biotechnology, and the ethical concerns that follow in its wake....

  7. Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores.

    Science.gov (United States)

    Elosegui-Artola, Alberto; Andreu, Ion; Beedle, Amy E M; Lezamiz, Ainhoa; Uroz, Marina; Kosmalska, Anita J; Oria, Roger; Kechagia, Jenny Z; Rico-Lastres, Palma; Le Roux, Anabel-Lise; Shanahan, Catherine M; Trepat, Xavier; Navajas, Daniel; Garcia-Manyes, Sergi; Roca-Cusachs, Pere

    2017-11-30

    YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Brain nuclear receptors and body weight regulation

    Science.gov (United States)

    Neural pathways, especially those in the hypothalamus, integrate multiple nutritional, hormonal, and neural signals, resulting in the coordinated control of body weight balance and glucose homeostasis. Nuclear receptors (NRs) sense changing levels of nutrients and hormones, and therefore play essent...

  9. Strategy for public understanding and participation in nuclear safety regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, H. J.; Chung, Yun Hyung

    2004-02-15

    The objective of this study is to help the general public and local residents to better understand and trust nuclear safety regulation. In order to obtain public confidence in nuclear safety regulation, the emotion and demand of public should be first understood and the change in an attitude to meet the present circumstances actively is requisite. Hence it is intended that a genuine communication shall be newly arranged and accomplished on the basis of mutual understanding. To achieve this, a series of public opinion poll have performed periodically and symposium for the public acceptance is held in order to frame a policy based on the understanding of nuclear safety and regulation of the general public and local residents. Besides nuclear safety indicators including safety sentiment indicators are being developed as a means to understand the safety of operating nuclear power plants from the viewpoint of the general public, a plan for the harmonious communication of nuclear safety information is established, and handbooks of nuclear terminologies and report-writing are under development in part. Finally plans for convergence of the public opinions and a wide public involvement in nuclear safety regulation are formulated and their applicability as organization and administration program is now under consideration.

  10. Between the Devil and the Deep Sea : The Netherlands and the Struggle for European Nuclear Order

    NARCIS (Netherlands)

    Hellendoorn, E.A.A.

    2016-01-01

    This dissertation is about the early history of the Netherlands nuclear non-proliferation policy. The book places the development of Dutch policy with regard to NATO nuclear policy, European integration and ultracentrifuge technology in an international perspective. The work moves beyond traditional

  11. Review of Policy Documents for Nuclear Safety and Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woong Sik; Choi, Kwang Sik; Choi, Young Sung; Kim, Hho Jung; Kim, Ho Ki [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of)

    2006-07-01

    The goal of regulation is to protect public health and safety as well as environment from radiological hazards that may occur as a result of the use of atomic energy. In September 1994, the Korean government issued the Nuclear Safety Policy Statement (NSPS) to establish policy goals of maintaining and achieving high-level of nuclear safety and also help the public understand the national policy and a strong will of the government toward nuclear safety. It declares the importance of establishing safety culture in nuclear community and also specifies five nuclear regulatory principles (Independence, Openness, Clarity, Efficiency and Reliability) and provides the eleven regulatory policy directions. In 2001, the Nuclear Safety Charter was declared to make the highest goal of safety in driving nuclear business clearer; to encourage atomic energy- related institutions and workers to keep in mind the mission and responsibility for assuring safety; to guarantee public confidence in related organizations. The Ministry of Science and Technology (MOST) also issues Yearly Regulatory Policy Directions at the beginning of every year. Recently, the third Atomic Energy Promotion Plan (2007-2011) has been established. It becomes necessary for the relevant organizations to prepare the detailed plans on such areas as nuclear development, safety management, regulation, etc. This paper introduces a multi-level structure of nuclear safety and regulation policy documents in Korea and presents some improvements necessary for better application of the policies.

  12. Dynamics and regulation of nuclear import and nuclear movements of HIV-1 complexes

    Science.gov (United States)

    Burdick, Ryan C.; Chen, Jianbo; Sastri, Jaya; Hu, Wei-Shau

    2017-01-01

    The dynamics and regulation of HIV-1 nuclear import and its intranuclear movements after import have not been studied. To elucidate these essential HIV-1 post-entry events, we labeled viral complexes with two fluorescently tagged virion-incorporated proteins (APOBEC3F or integrase), and analyzed the HIV-1 dynamics of nuclear envelope (NE) docking, nuclear import, and intranuclear movements in living cells. We observed that HIV-1 complexes exhibit unusually long NE residence times (1.5±1.6 hrs) compared to most cellular cargos, which are imported into the nuclei within milliseconds. Furthermore, nuclear import requires HIV-1 capsid (CA) and nuclear pore protein Nup358, and results in significant loss of CA, indicating that one of the viral core uncoating steps occurs during nuclear import. Our results showed that the CA-Cyclophilin A interaction regulates the dynamics of nuclear import by delaying the time of NE docking as well as transport through the nuclear pore, but blocking reverse transcription has no effect on the kinetics of nuclear import. We also visualized the translocation of viral complexes docked at the NE into the nucleus and analyzed their nuclear movements and determined that viral complexes exhibited a brief fast phase (nuclear import, viral core uncoating, and intranuclear movements that precede integration site selection. PMID:28827840

  13. Hybrid cardiac imaging: SPECT/CT and PET/CT. A joint position statement by the European Association of Nuclear Medicine (EANM), the European Society of Cardiac Radiology (ESCR) and the European Council of Nuclear Cardiology (ECNC)

    DEFF Research Database (Denmark)

    Flotats, Albert; Gutberlet, Matthias; Knuuti, Juhani

    2011-01-01

    improvement in the management of patients with cancer over stand-alone acquired CT and PET images. Hybrid cardiac imaging either with single photon emission computed tomography (SPECT) or PET combined with CT depicts cardiac and vascular anatomical abnormalities and their physiologic consequences in a single....... The European Association of Nuclear Medicine (EANM), the European Society of Cardiac Radiology (ESCR) and the European Council of Nuclear Cardiology (ECNC) in this paper want to present a position statement of the institutions on the current roles of SPECT/CT and PET/CT hybrid cardiac imaging in patients...

  14. Nuclear receptors and microRNAs: who regulates the regulators in neural stem cells?

    NARCIS (Netherlands)

    Eendebak, R.J.A.H.; Lucassen, P.J.; Fitzsimons, C.P.

    2011-01-01

    In this mini-review, we focus on regulatory loops between nuclear receptors and microRNAs, an emerging class of small RNA regulators of gene expression. Evidence supporting interactions between microRNAs and nuclear receptors in the regulation of gene expression networks is discussed in relation to

  15. Liberalization and regulation. European lessons and Colombian trends

    Directory of Open Access Journals (Sweden)

    Pedro Ignacio Bernal Forero

    2010-06-01

    Full Text Available This article reviews the consequences of liberalization and regulation processes on services of general interest in Europe, in the context of economic integration. It highlights the differences observed between network utilities like telecommunications, electricity and gas, on the one hand, and drinking water or services of a social nature, on the other hand. The article analyzes why the latter have enjoyed a rather special status when it comes to applying the rules of competition, and it discusses the legal treatment given by the European Commission to the public subsidies which these services receive. Finally, certain parallels have been drawn with public utilities in Colombia since the 1990s.

  16. European Medical Device Directive : impact on nuclear medicine

    NARCIS (Netherlands)

    Kuyvenhoven, JD; Lahorte, P; Persyn, K; De Geest, E; van Loon, PW; Jacobs, F; van Rijk, PP; Lemahieu, [No Value; Dierckx, R A

    2001-01-01

    The European Council Directive 93/42/EEC concerning medical devices (14 June 1993) assigns new responsibilities and imposes technical requirements both to the manufacturer and user of medical devices. In this paper the general outlines of the directive are discussed with a particular emphasis on the

  17. State-federal interactions in nuclear regulation

    Energy Technology Data Exchange (ETDEWEB)

    Pasternak, A.D.; Budnitz, R.J.

    1987-12-01

    The Atomic Energy Act of 1954 established, and later Congressional amendments have confirmed, that except in areas which have been explicitly granted to the states, the federal government possesses preemptive authority to regulate radiation hazards associated with the development and use of atomic energy. Since the passage of the original Act, numerous decisions by the courts have reaffirmed the legitimacy of federal preemption, and have defined and redefined its scope. In this study, the aim is to explore the underlying issues involved in federal preemption of radiation-hazard regulation, and to recommend actions that the Department of Energy and other agencies and groups should consider undertaking in the near term to protect the preemption principle. Appropriate roles of the states are discussed, as well as recent state-level activities and their rationale, and several current arenas in which state-federal conflicts about regulation of hazards are being played out. The emphasis here is on four particular arenas that are now important arenas of conflict, but the issues discussed are far broader in scope. These four arenas are: state-level moratorium activity; emergency planning for reactors; conflicts arising from state financial regulation; and inroads in federal preemption through litigation under state law.

  18. Euratom research and training in nuclear reactor safety: Towards European research and the higher education area

    Energy Technology Data Exchange (ETDEWEB)

    Goethem, G. van [Nuclear Fission and Radiation Protection European Commission, Building MO75-5-34, B-1049 Brussels (Belgium)]. E-mail: georges.van-goethem@cec.eu.int

    2004-07-01

    In this invited lecture, research and training in nuclear fission are looked at from a European perspective with emphasis on the three success factors of any European policy, namely: common needs, vision and instruments, that ought to be strongly shared amongst the stakeholders across the Member States concerned. As a result, the following questions are addressed: What is driving the current EU trend towards more research, more education and more training, in general? Regarding nuclear fission, in particular, who are the end-users of Euratom 'research and training' and what are their expectations from EU programmes? Do all stakeholders share the same vision about European research and training in nuclear fission? What are the instruments proposed by the European Commission (EC) to conduct joint research programmes of common interest for the nuclear fission community? In conclusion, amongst the stakeholders in Europe, there seems to be a wide consensus about common needs and instruments, but not about a common vision regarding nuclear. (author)

  19. The Nuclear Revival - A European and US Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Bouttes, J.P.; Geckle, M.

    2007-07-01

    Europe and the U.S share an history of almost five decades of use of nuclear energy for electricity generation, and they still represent the bulk of it. However, new investments were almost totally stopped for many years, in the US first--essentially for economic reasons--and then in Europe, for more complex reasons, including the consequences of the Chernobyl accident. Today, there are clear signs of a nuclear revival on both sides of the Atlantic Ocean ; this paper deals with the drivers of this revival, the conditions to be satisfied for a transformation of these first signs into a real revival, the possible extent of it, and the consequences for the rest of the world. (auth)

  20. Mycotoxins: Risks, regulations and European co-operation

    Directory of Open Access Journals (Sweden)

    Van Egmond Hans P.

    2013-01-01

    Full Text Available Mycotoxins and mycotoxicises have been problems of the past and the present, but scientific attention for mycotoxins did not start until the early 1960’s. Nowa­days, many mycotoxins are known, and their occurrence in food and animal feed may cause various adverse effects on human and animal health, including carcinogenic, hepatotoxic, immunotoxic, nephrotoxic, neurotoxic, oestrogenic and teratogenic effects. Some important mycotoxins include the aflatoxins, ochratoxin A, the fumonisins and the trichothecenes, and their significance is briefly described. To protect human and animal health, many countries have enacted specific regulations for mycotoxins in food and animal feed. Risk assessment is a major factor for scientific underpinning of regulations, but other factors such as availability of adequate sampling and analysis procedures also play an important a role in the establishment of mycotoxin regulations. In addition, socio-economic factors such as cost-benefit considerations, trade issues and sufficiency of food supply are equally important in the decision-taking process to come to meaningful regulations. Nowadays, more than 100 countries have formal mycotoxin regulations for food and feed. The mycotoxin regulations are the most stringent in the EU, where various organizations and pan-European networks contribute to combat the mycotoxin problem. It is to be expected that mycotoxins will stay with us in the future and climate change might have a negative influence in this respect. Several possibilities exist to mitigate the problems caused by mycotoxins. In particular prevention of mould growth and mycotoxin formation is key to the control of mycotoxins.

  1. The role of research in nuclear regulation: A Korean perspective

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Won-Hyo [Korea Institute of Nuclear Safety, Tajeon (Korea, Republic of)

    1997-01-01

    Korea has carried out a very ambitious nuclear power program since the 1970`s as part of the nation`s industrialization policy. Ever since, Korea has also maintained a strong commitment to nuclear power development as an integral part of the national energy policy which aims at reducing external vulnerability and ensuring against a global fossil fuel shortage. The introduction of nuclear power into Korea has progressed through three stages: the first was a turn-key package supplied by the manufacturer; the second involved a major contractor who was responsible for project management, and design and construction was contracted out, with Korean industry becoming more involved; the third stage has seen Korean industries involved as main contractors based on experience gained from earlier plants. The success of Korea`s nuclear power program depends in large part on how to insure safety. Safety has the highest priority in nuclear energy development. Public acceptance has been the most critical problem faced by the nuclear industry in Korea. The public demands the highest level of safety all through the design, construction, and operation of nuclear power plants. Korea has learned that a nuclear plant designed with well addressed safety, implementation of a well grounded QA program during construction, and operated with a proven record of safety, are the only ways to earn public support. Competent and efficient regulation with a strong safety culture and openness in all issues is the most desirable image for regulators to strive for. Korea established a ten year R & D program to obtain self-reliance in nuclear technology and international competitiveness by the early 2000`s in 1992. It has actively participated in coordinated research programs in safety issues with bodies including the USNRC, AECB of Canada, IAEA, and OECD/NEA.

  2. Nuclear localization signal regulates porcine circovirus type 2 capsid protein nuclear export through phosphorylation.

    Science.gov (United States)

    Hou, Qiang; Hou, Shaohua; Chen, Qing; Jia, Hong; Xin, Ting; Jiang, Yitong; Guo, Xiaoyu; Zhu, Hongfei

    2018-02-15

    The open reading frame 2 (ORF2) of Porcine circovirus type 2 (PCV2) encodes the major Capsid (Cap) protein, which self-assembles into virus-like particle (VLP) of similar morphology to the PCV2 virion and accumulates in the nucleus through the N-terminal arginine-rich nuclear localization signal (NLS). In this study, PCV2 Cap protein and its derivates were expressed via the baculovirus expression system, and the cellular localization of the recombinant proteins were investigated using anti-Cap mAb by imaging flow cytometry. Analysis of subcellular localization of Cap protein and its variants demonstrated that NLS mediated Cap protein nuclear export as well as nuclear import, and a phosphorylation site (S17) was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the NLS domain to regulate Cap protein nuclear export. Phosphorylation of NLS regulating the PCV2 Cap protein nuclear export was also demonstrated in PK15 cells by fluorescence microscopy. Moreover, the influence of Rep and Rep' protein on Cap protein subcellular localization was investigated in PK15 cells. Phosphorylation of NLS regulating Cap protein nuclear export provides more detailed knowledge of the PCV2 viral life cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. A Role for Phosphoinositides in Regulating Plant Nuclear Functions

    Science.gov (United States)

    Dieck, Catherine B.; Boss, Wendy F.; Perera, Imara Y.

    2012-01-01

    Nuclear localized inositol phospholipids and inositol phosphates are important for regulating many essential processes in animal and yeast cells such as DNA replication, recombination, RNA processing, mRNA export and cell cycle progression. An overview of the current literature indicates the presence of a plant nuclear phosphoinositide (PI) pathway. Inositol phospholipids, inositol phosphates, and enzymes of the PI pathway have been identified in plant nuclei and are implicated in DNA replication, chromatin remodeling, stress responses and hormone signaling. In this review, the potential functions of the nuclear PI pathway in plants are discussed within the context of the animal and yeast literature. It is anticipated that future research will help shed light on the functional significance of the nuclear PI pathway in plants. PMID:22645589

  4. Peripheral processing utilisation in CDC 6000 series machines at the European Nuclear Research Centre (CERN), Geneva

    CERN Document Server

    Letts, P J

    1972-01-01

    This paper gives some results from monitoring peripheral processor activity on CDC 6000 series machines at the European Nuclear Research Centre (CERN). It relates peripheral processor activity to a (single) central processor and argues that such an architecture is more likely to meet future user demands for higher levels of multiprogramming data security and error recovery. (12 refs).

  5. The Eurosafe Forum 2003: Nuclear expertise and challenges of the enlargement of the European Union

    Energy Technology Data Exchange (ETDEWEB)

    Lacronique, Jean-Francois; Repussard, Jacques (eds.) [Institut de Radioprotection et de Surete Nucleaire, IRSN, B.P. 17, F - 92262 Fontenay-aux-Roses Cedex (France); Hahn, Lothar (ed.) [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH, GRS, Schwertnergasse 1, D - 50667 Koeln (Germany)

    2003-07-01

    EUROSAFE is an international forum for discussions among experts from technical safety organisations, research institutes, safety authorities, utilities, the industry, public authorities and non-governmental organisations concerning the status of and recent achievements in nuclear installation safety, waste management, radiation safety and nuclear material security. The Eurosafe Forum 2003 - the fifth of its kind - was held at the Palais Brongniart in Paris on November 25 and 26, 2003. This year's theme was: 'Nuclear expertise and challenges of the enlargement of the European Union: speakers in the various European countries about the environmental scan before enlargement, development and structuring perspectives within the enlarged Europe'. The event brought together 445 experts and researchers from around the world (including 124 from Germany, 184 from France, 88 from Eastern Europe, as well as representatives from Korea, Japan, the United States, Canada, Cuba, and Armenia. The proceedings of the symposium can now be consulted online. The fifth edition of the forum focused on nuclear expertise and the challenge of EU-enlargement and the latest work carried out by GRS, IRSN and their partners from the European Union, Switzerland and Eastern Europe. Nuclear energy contributes approximately one third of European electricity production. A high level of nuclear safety is a priority for the countries of Europe. The technical safety organisations play an important role in contributing to that objective through appropriate approaches to major safety issues as part of their assessments and research activities. The challenges to nuclear safety are increasingly international. Changes in underlying technologies such as instrumentation and control, the impact of electricity market deregulation, demands for improved safety, the ageing of nuclear facilities, waste management, maintaining and improving scientific and technical knowledge and the need for greater

  6. Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships.

    Directory of Open Access Journals (Sweden)

    Pranali P Pathare

    Full Text Available Mammalian nuclear receptors broadly influence metabolic fitness and serve as popular targets for developing drugs to treat cardiovascular disease, obesity, and diabetes. However, the molecular mechanisms and regulatory pathways that govern lipid metabolism remain poorly understood. We previously found that the Caenorhabditis elegans nuclear hormone receptor NHR-49 regulates multiple genes in the fatty acid beta-oxidation and desaturation pathways. Here, we identify additional NHR-49 targets that include sphingolipid processing and lipid remodeling genes. We show that NHR-49 regulates distinct subsets of its target genes by partnering with at least two other distinct nuclear receptors. Gene expression profiles suggest that NHR-49 partners with NHR-66 to regulate sphingolipid and lipid remodeling genes and with NHR-80 to regulate genes involved in fatty acid desaturation. In addition, although we did not detect a direct physical interaction between NHR-49 and NHR-13, we demonstrate that NHR-13 also regulates genes involved in the desaturase pathway. Consistent with this, gene knockouts of these receptors display a host of phenotypes that reflect their gene expression profile. Our data suggest that NHR-80 and NHR-13's modulation of NHR-49 regulated fatty acid desaturase genes contribute to the shortened lifespan phenotype of nhr-49 deletion mutant animals. In addition, we observed that nhr-49 animals had significantly altered mitochondrial morphology and function, and that distinct aspects of this phenotype can be ascribed to defects in NHR-66- and NHR-80-mediated activities. Identification of NHR-49's binding partners facilitates a fine-scale dissection of its myriad regulatory roles in C. elegans. Our findings also provide further insights into the functions of the mammalian lipid-sensing nuclear receptors HNF4α and PPARα.

  7. Application of Nuclear Regulatory Commission Regulation Equivalency to Construction of New Nuclear Facilities

    Energy Technology Data Exchange (ETDEWEB)

    BISHOP, G.E.

    1999-06-02

    The Spent Nuclear Fuels Project (SNFP) Office of the Department of Energy (DOE), Richland Operations Office, is charged with moving 2.100 metric tons of spent nuclear fuel elements left over from plutonium production into semi-permanent storage at DOE'S Hanford site in Washington state. In anticipation of eventual NRC regulation, the DOE decided to impose NRC requirements on new SNFP facility design and construction, specifically for the Cold Vacuum Drying Facility (CVDF) and the Canister Storage Building (CSB). The SNFP implemented this policy of ''NRC equivalency'' with the goal of achieving a level of nuclear safety equivalent to that of NRC-licensed fuel processing facilities. Appropriate features of the NRC licensing process were adopted. However, the SNFP maintained applicable DOE requirements in tandem with the NRC regulations. Project work is continuing, with the first fuel movement scheduled for November, 2000.

  8. 78 FR 71675 - Update of the Office of Nuclear Reactor Regulation's Electronic Operating Reactor Correspondence

    Science.gov (United States)

    2013-11-29

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Update of the Office of Nuclear Reactor Regulation's Electronic Operating Reactor Correspondence... Regulatory Commission. Michele G. Evans, Director, Division of Operating Reactor Licensing, Office of Nuclear...

  9. Highlights of the annual congress of the European Association of Nuclear Medicine, Copenhagen 2007

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, Juhani [Turku University Central Hospital, Turku PET Centre, P.O. Box 52, Turku (Finland); Hustinx, Roland [University Hospital of Liege, Division of Nuclear Medicine, Liege (Belgium)

    2008-03-15

    The Annual Congress of the European Association of Nuclear Medicine took place in Copenhagen on October 13-17, 2007. The event is the major scientific and professional effort in the field of nuclear medicine in Europe. The most important developments in the fields of instrumentation, radionuclide production, radiochemistry, radiotherapy, as well as the clinical imaging fields of neurology, cardiology, oncology, and general sciences were reported. This paper emphasizes the major findings and trends at this important gathering. This review is, however, only a brief summary of the large amount of data discussed. (orig.)

  10. Regulatory or regulating publics? The European Union's regulation of emerging health technologies and citizen participation.

    Science.gov (United States)

    Flear, Mark L; Pickersgill, Martyn D

    2013-01-01

    'Citizen participation' includes various participatory techniques and is frequently viewed as an unproblematic and important social good when used as part of the regulation of the innovation and implementation of science and technology. This is perhaps especially evident in debates around 'anticipatory governance' or 'upstream engagement'. Here, we interrogate this thesis using the example of the European Union's regulation of emerging health technologies (such as nanotechnology). In this case, citizen participation in regulatory debate is concerned with innovative objects for medical application that are considered to be emergent or not yet concrete. Through synthesising insights from law, regulatory studies, critical theory, and science and technology studies, we seek to cast new light on the promises, paradoxes, and pitfalls of citizen participation as a tool or technology of regulation in itself. As such we aim to generate a new vantage point from which to view the values and sociotechnical imaginaries that are both 'designed-in' and 'designed-out' of citizen participation. In so doing, we show not only how publics (do not) regulate technologies, but also how citizens themselves are regulated through the techniques of participation.

  11. Revised seismic and geologic siting regulations for nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, A.J.; Chokshi, N.C. [Office of Nuclear Regulatory Research, Washington, DC (United States)

    1997-02-01

    The primary regulatory basis governing the seismic design of nuclear power plants is contained in Appendix A to Part 50, General Design Criteria for Nuclear Power Plants, of Title 10 of the Code of Federal Regulations (CFR). General Design Criteria (GDC) 2 defines requirements for design bases for protection against natural phenomena. GDC 2 states the performance criterion that {open_quotes}Structures, systems, and components important to safety shall be designed to withstand the effects of natural phenomena such as earthquakes, . . . without loss of capability to perform their safety functions. . .{close_quotes}. Appendix A to Part 100, Seismic and Geologic Siting Criteria for Nuclear Power Plants, has been the principal document which provided detailed criteria to evaluate the suitability of proposed sites and suitability of the plant design basis established in consideration of the seismic and geologic characteristics of the proposed sites. Appendix A defines required seismological and geological investigations and requirements for other design conditions such as soil stability, slope stability, and seismically induced floods and water waves, and requirements for seismic instrumentation. The NRC staff is in the process of revising Appendix A. The NRC has recently revised seismic siting and design regulations for future applications. These revisions are discussed in detail in this paper.

  12. Regulation of Nuclear Localization of Signaling Proteins by Cytokinin

    Energy Technology Data Exchange (ETDEWEB)

    Kieber, J.J.

    2010-05-01

    Cytokinins are a class of mitogenic plant hormones that play an important role in most aspects of plant development, including shoot and root growth, vascular and photomorphogenic development and leaf senescence. A model for cytokinin perception and signaling has emerged that is similar to bacterial two-component phosphorelays. In this model, binding of cytokinin to the extracellular domain of the Arabidopsis histidine kinase (AHKs) receptors induces autophosphorylation within the intracellular histidine-kinase domain. The phosphoryl group is subsequently transferred to cytosolic Arabidopsis histidine phosphotransfer proteins (AHPs), which have been suggested to translocate to the nucleus in response to cytokinin treatment, where they then transfer the phosphoryl group to nuclear-localized response regulators (Type-A and Type-B ARRs). We examined the effects of cytokinin on AHP subcellular localization in Arabidopsis and, contrary to expectations, the AHPs maintained a constant nuclear/cytosolic distribution following cytokinin treatment. Furthermore, mutation of the conserved phosphoacceptor histidine residue of the AHP, as well as disruption of multiple cytokinin signaling elements, did not affect the subcellular localization of the AHP proteins. Finally, we present data indicating that AHPs maintain a nuclear/cytosolic distribution by balancing active transport into and out of the nucleus. Our findings suggest that the current models indicating relocalization of AHP protein into the nucleus in response to cytokinin are incorrect. Rather, AHPs actively maintain a consistent nuclear/cytosolic distribution regardless of the status of the cytokinin response pathway.

  13. The nuclear and radiological regulation in Mexico; La regulacion nuclear y radiologica en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Carreno P, A. L.; Cuecuecha J, M. E., E-mail: alcarreno@cnsns.gob.mx [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Barragan No. 779, Col. Narvarte, 03020 Mexico D. F. (Mexico)

    2012-10-15

    The regulation in nuclear and radiological safety matter in Mexico is in constant development, attended the workers necessities, the society and the environment. The present work exposes and gives to know the process to emit a Mexican Official Standard of the Nucl series, also enunciates the dependences and institutions that participate in the process, the main identified challenges for its elaboration, emission and revision, and finally are mentioned the topics that in the present are in this process. (Author)

  14. Lobbying in the European union – regulation and public sector economics perspective

    Directory of Open Access Journals (Sweden)

    Daniela Dvořáková

    2013-01-01

    Full Text Available Lobbying has become an inseparable companion of the decision-making process and firms but also other social actors (non-governmental organizations, individuals, private and civil sector are forced to reflect this fact, if they want to promote their interests effectively and if they want to avoid regulation that would harm their interests. The paper analyses the regulation of lobbying in European institutions and focuses on two major institutions which are under pressure of the lobbyists, the European Commission and the European Parliament. The paper discusses and presents the both ways of regulation which occur in the European institutions- the concept of self-regulation and the binding Code of Conduct under the Rules of Procedure in the European Parliament.The paper contains also possible economic consequences of lobbying based on the Public Sector Economics perspective and the methodology of the principal-agent relationship.

  15. CONSIDERATION REGARDING TO THE FISCAL REGULATIONS IN SOME EUROPEAN STATES

    Directory of Open Access Journals (Sweden)

    Ardeleanu-Popa Carmen

    2010-12-01

    Full Text Available It can be observed, that the member states of the European Union were guided to implement some reforms in the domain of fiscal politics, the aim of which would constitute in fighting and eliminating the damaging fiscal competition, of the differences regarding to indirect fiscality, etc. Without this political fiscal instrument coordinated by the members of the European Union, the free traffic of capitals could be transformed into a determinant factor of the cross-border fraud.

  16. Issues in space segment regulation in the european community

    Science.gov (United States)

    Verhoef, Paul

    A major restructuring of the satellite communications market in the European Community has been set in motion with the advent of the European Commission's Satellite Green Paper. The first detailed proposals for Community legislation however, address mainly ground segment issues, such as type-approval of satellite equipment and the mutual recognition of licences. Space segment issues remain an important area for further reflection. This paper presents some background to these space segment issues within the context of the Community satellite communications policy.

  17. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

    Science.gov (United States)

    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  18. Arenas for risk governance in nuclear waste management - The European Union ARGONA Project

    Energy Technology Data Exchange (ETDEWEB)

    Jonsson, Josefin P.; Wetzel, Carina (Swedish Radiation Safety Authority, SE-171 16 Stockholm (Sweden)); Andersson, Kjell; Lidberg, Maria (Karita Research AB, Box 6048, SE-187 06 Taeby (Sweden))

    2009-12-15

    There is a large knowledge base about governance issues but how to implement the new processes of transparency and participation is not self-evident. In other words there is a common demand for bridging the gap between research and implementation for the governance of nuclear waste management. There are legal, organizational, historical and cultural factors that set conditions which have to be understood for effective implementation. We must also understand how deliberative methods and the transparency approach relate to each other, and to formal decision-making in representative democracy. Therefore, the ARGONA project intends to demonstrate how participation and transparency link to the political and legal systems and how new approaches can be implemented in nuclear waste management programmes. For this purpose, the project includes: Studies of the context within which processes of participation and transparency take place, in order to understand how the processes can be used in the waste management programs. Studies of theory - in order to build participation and transparency on a firm ground; Case studies - to understand how different processes work; Implementation - to make a difference, learn and demonstrate. The project now approaches its finalization and it is foreseen that the reporting, in addition to 25 deliverables to the European Commission, will include a full final report, a summary final report and recommendations with proposed guidelines that can be considered by national actors of nuclear waste programmes as well as the European Commission

  19. Radiation protection and regulations for the nuclear medicine physician.

    Science.gov (United States)

    Chen, Man Yu

    2014-05-01

    As authorized users of radioactive material, nuclear medicine (NM) physicians play a leading role in the use and management of these agents. Regarding patient management, NM physicians are responsible for ensuring both the appropriateness of exams and the associated patient doses. Along with radiologists, NM physicians are the ones developing and implementing processes that provide guidance to and dialog with referring physicians to ensure that patients receive the most appropriate type of imaging exams. Regarding regulatory compliance, in collaboration with radiation safety officers, NM physicians are the ones educating their staff about principles of radiation protection and radiation safety with adherence to regulations from agencies such as the Nuclear Regulatory Commission, the Department of Transportation, the Environmental Protection Agency, and the Food and Drug Administration. On occasion, these regulations and standards can be difficult to comprehend. This article is intended to serve as a condensed guide for NM physicians who are in the process of applying for a radioactive materials license, establishing a new radiation protection program, or want to ensure continued compliance and maintenance of safety and security of licensed materials in the clinical or research settings. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Governmental policies and measures regulating nitrogen and phosphorus from animal manure in European Agriculture

    NARCIS (Netherlands)

    Oenema, O.

    2005-01-01

    This paper discusses governmental policies and measures that regulate the use of animal manure in the European Union (EU-15). Systematic intervention by governments with European agriculture in general started at the end of the 19th century. Major changes in governmental policies on agriculture

  1. Reasons for Regulating Informal Relationships: A comparison of nine European jurisdictions

    NARCIS (Netherlands)

    Mol, C.R.

    In Europe, informal relationships have been increasing in number. While the regulation of informal relationships is recent and relatively limited, nine European jurisdictions have taken legislative action and adopted a lex specialis for informal relationships. This article takes a comparative

  2. Franco-German nuclear cooperation: from the `common product` to the first European pressurized water reactor

    Energy Technology Data Exchange (ETDEWEB)

    Vignon, D. [Societe Franco-Americaine de Constructions Atomiques (FRAMATOME), 92 - Paris-la-Defense (France)

    1999-01-01

    It has now been 10 years since Framatome and Siemens decided to collaborate on the design and sales of an advanced nuclear power plant (NPP) model based on pressurized water reactor (PWR) technology. Originally called the `common product`, this model was renamed the European pressurized water reactor when Electricite de France (EDF) and the German electric utilities joined this cooperative development effort in 1992. Since the beginning, this cooperation has been formalized in the framework of an agreement that led to the founding of a joint and equally owned subsidiary, Nucler Power International (NPI), which is reponsible for leading the development of the new model and later handling its export sales.

  3. Electronic signatures and their specificity in national and European regulations

    Directory of Open Access Journals (Sweden)

    R. MATEFI

    2017-07-01

    Full Text Available The paper aims to emphasize the particularities of the electronic signature by reference to the national as well as to the European legislation, trying to point out its utility in the business environment as well as the controversies in this matter. The starting point of this analysis was the Directive 1999/93/EC of the European Parliament and of the Council of 13 December 1999 on a Community framework for electronic signatures, which establishes the legal framework for electronic signatures and the recognition of certification-service providers. Its main aim was to ease its use and help it become legally recognized within all EU countries.

  4. Monte Carlo tools evaluation for nuclear analyses of the European DEMO

    Energy Technology Data Exchange (ETDEWEB)

    Jaboulay, Jean-Charles, E-mail: jean-charles.jaboulay@cea.fr [CEA-Saclay, DEN, DM2S, SERMA, LPEC, F-91191 Gif-sur-Yvette (France); Damian, Frédéric [CEA-Saclay, DEN, DM2S, SERMA, LPEC, F-91191 Gif-sur-Yvette (France); Aiello, Giacomo [CEA-Saclay, DEN, DM2S, SEMT, LISN, F-91191 Gif-sur-Yvette (France); Taylor, David; Zheng, Shanliang [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Bienkowska, Barbara; Drozdowicz, Krzysztof; Tracz, Grzegorz [IPPLM, Warsaw/IFJ Krakow (Poland); Fischer, Ulrich [KIT – Karlsruhe Institute of Technology, Karlsruhe (Germany); Bachmann, Christian [EFDA – European Fusion Development Agreement, Garching (Germany)

    2015-10-15

    This paper presents the status of different Monte Carlo (MC) particle transport codes regarding their capabilities to model the European fusion power demonstration reactor (DEMO). This work was carried out, via a collaboration between CEA, CCFE, IPPLM and KIT to evaluate MC codes which could replace MCNP for nuclear analysis on DEMO. Each association has participated using a different MC code: CEA with TRIPOLI-4, CCFE with Serpent, and IPPLM with FLUKA. The common DEMO model studied has been developed by KIT with MCNP. Considerable effort was required to translate the MCNP input deck into the syntax of Serpent and FLUKA codes; so no real nuclear analysis has been performed in the frame of this work. Regarding TRIPOLI-4, a benchmark has been successfully conducted; the results obtained are statistically similar to those of MCNP with comparable computation times.

  5. Collective dose to the European Community from nuclear industry effluents discharge in 1978

    CERN Document Server

    Camplin, W C

    1983-01-01

    The results are presented of a study to evaluate the collective dose commitment to the population of the European Community from effluents released by the nuclear industry within the EC in 1978. Airborne and liquid effluent discharge data have been taken from published sources, and computer modelling techniques have been used to predict the transfer of radioactivity through the environment to man. The collective dose commitments due to discharges from each nuclear installation have been evaluated and the comparative significance of individual radionuclides and their pathways to man have been considered. Airborne releases resulted in an estimated collective effective dose equivalent commitment of 95 man Sv, the major part of which is due to carbon-14 from both power stations and reprocessing plants. The collective effective dose equivalent commitment from liquid effluents is estimated to be 408 man Sv, mostly due to caesium-137 and other radionuclides from the Sellafield (formerly Windscale) reprocessing plant...

  6. France's contribution to the construction of the European regulatory framework for nuclear safety; Le role de la France dans l'elaboration d'un cadre reglementaire europeen

    Energy Technology Data Exchange (ETDEWEB)

    Etienne, Ph. [France aupres de l' Union europeenne, Bruxelles (Belgium)

    2010-11-15

    As a key player in the nuclear industry, France has worked constantly to consolidate the EURATOM requirements and to develop the legislation derived from them. The recent upsurge in interest in nuclear power has led the European Commission, supported by France, to produce a true community safety framework, the principles of which are presented in the 2000 Green Paper. The initial debate on the 'nuclear package' was followed by a period of reflection and discussion which began at a European level, in particular outside strictly community circles, with the WENRA group (Western European Nuclear Regulators Association). It was also at that time that France acquired an enhanced safety framework with the adoption of the 'Transparency and Security in the Nuclear Field' Act of 2006. In March 2007, the European Council was to give the necessary impetus for reviving the Community process. ENSREG and the European Nuclear Energy Forum contributed to the Community debate on safety, waste management and transparency. This debate was to continue under the French Presidency with the adoption of a resolution on the management of waste and of spent fuel, along with initial discussions around the 'Safety' directive adopted several months later by the Czech Presidency. The efforts of the Commission and of France continued, in particular with a proposed directive concerning the management of waste and spent fuel, planned for autumn of 2010. (author)

  7. Formulating European work and employment regulation during the pre-crisis years

    DEFF Research Database (Denmark)

    Mailand, Mikkel; Arnholtz, Jens

    2015-01-01

    This article discusses whether the pre-crisis political right-turn in the European Union (EU) has had an impact on the development of European work and employment regulation. It finds that although pro-regulation actors have been weakened in the year leading up to the crisis, the expected weakening...... of Social Europe is only seen in a minority of the eight cases of EU-level work and employment regulation analysed. It is argued that two mechanisms can help explain this weaker than expected impact: successful resistance from pro-regulation actors and a certain form of organizational inertia linked...

  8. CHANDA and ERINDA: Joint European programs for research on safety of nuclear facilities and waste reduction

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, Roland; Hannaske, Roland; Koegler, Toni [Institut fuer Strahlenphysik, Helmholtz Zentrum DD-Rossendorf, 01328 Dresden (Germany); Institut fuer Kern- und Teilchenphysik, TU Dresden, 01069 Dresden (Germany); Grosse, Eckart [Institut fuer Kern- und Teilchenphysik, TU Dresden, 01069 Dresden (Germany); Junghans, Arnd R. [Institut fuer Strahlenphysik, Helmholtz Zentrum DD-Rossendorf, 01328 Dresden (Germany)

    2014-07-01

    In spite of the planned termination of the German nuclear power program neutron beam facilities in Germany can contribute considerably to research studies on the reduction of hazards due to nuclear waste. Transnational research programs support EU groups who want to carry out projects at the new tof set-up nELBE at HZDR, the calibrated n-flux at PTB and the FRANZ accelerator under construction at Frankfurt. Vice versa various facilities in the EU offer beams for transmutation and safety related studies with neutrons to German scientists under support by ERINDA (2011-2013) and CHANDA (2014-2017; solving challenges in nuclear data for the safety of European nuclear facilities). For work in that field scientific visits are also fostered to improve the exchange of experience between the partners (13 and in future about 35 from 18 countries). Plans for new projects as well as results obtained so far are discussed, and special emphasis is given to the present research performed at nELBE on neutron scattering and absorption.

  9. Regulation and the Ownership Structure of European Listed Firms

    DEFF Research Database (Denmark)

    Rapp, Marc Steffen; Trinchera, Oliver

    2017-01-01

    In this paper, we explore an extensive panel data set covering more than 4,000 listed firms in 16 European countries to study the effects of shareholder protection on ownership structure and firm performance. We document a negative firm-level correlation between shareholder protection and ownersh...

  10. Risk, Territory and Society : Challenge for a Joint European Regulation

    NARCIS (Netherlands)

    Van Breugel, K.; Ale, B.J.M.; Basta, C.

    In 2004, the Major Accidents Hazards Bureau of the Joint Research Centre of the European Commission launched the “Land Use Planning Including MAHB and NEDIES” research programme, in the context of which most of the research collected in this book was conducted. The focus of the investigation was on

  11. Directives and regulations of the European Union on the protection of the environment

    Directory of Open Access Journals (Sweden)

    Salma Jožef

    2011-01-01

    Full Text Available The author of this paper analyzes the directives and regulations of the European Union pertaining to the protection of environment (water, air and soil. Since emissions frequently exceed local communities and regions, thus gain cross border, and sometimes even global effects, the directives and regulations of the European Union aim to provide bases for the harmonization of national laws in the European Union, as far as the registry of holders of dangerous things or providers of dangerous services, and the measures necessary to settle the consequences of pollution and means of preventing larger-scale environmental damages are concerned.

  12. Regulation of nucleotide excision repair by nuclear lamin b1.

    Directory of Open Access Journals (Sweden)

    Veronika Butin-Israeli

    Full Text Available The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1 in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.

  13. A study in improvement of administrative system in the nuclear safety regulation

    Energy Technology Data Exchange (ETDEWEB)

    Yook, Dong Il; Kuk, Doe Hyeong; Lee, Seong Min; Kim, Jong Sam; Hwang, Sun Ho [Chungnam National Univ., Taejon (Korea, Republic of)

    2001-03-15

    One of the most important tasks to improve nuclear safety regulation system is to separate nuclear regulatory institutes from public agencies which promote the development nuclear power. Moreover, nuclear safety regulation should be not only specialized but optimized to be adapted for new environments such as high-tech information age. Especially, it is necessary to reform the current nuclear safety regulation systems both to be effective under the local self-administration which began to operate in recent years and to be supported by local residents.

  14. Aircraft LTO emissions regulations and implementations at European airports

    Science.gov (United States)

    Yunos, Siti Nur Mariani Mohd; Ghafir, Mohammad Fahmi Abdul; Wahab, Abas Ab

    2017-04-01

    Aviation affects the environment via the emission of pollutants from aircraft, impacting human health and ecosystem. Impacts of aircraft operations at lower ground towards local air quality have been recognized. Consequently, various standards and regulations have been introduced to address the related emissions. This paper discussed both environmental regulations by focusing more on the implementations of LTO emissions charges, an incentive-based regulation introduced in Europe as an effort to fill the gap in addressing the environmental issues related to aviation.

  15. Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation

    Science.gov (United States)

    Wong, Madeline M; Guo, Chun; Zhang, Jinsong

    2014-01-01

    Nuclear receptor corepressor (NCoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT) function as corepressors for diverse transcription factors including nuclear receptors such as estrogen receptors and androgen receptors. Deregulated functions of NCoR and SMRT have been observed in many types of cancers and leukemias. NCoR and SMRT directly bind to transcription factors and nucleate the formation of stable complexes that include histone deacetylase 3, transducin b-like protein 1/TBL1-related protein 1, and G-protein pathway suppressor 2. These NCoR/SMRT-interacting proteins also show deregulated functions in cancers. In this review, we summarize the literature on the mechanism, regulation, and function of the core components of NCoR/SMRT complexes in the context of their involvement in cancers and leukemias. While the current studies support the view that the corepressors are promising targets for cancer treatment, elucidation of the mechanisms of corepressors involved in individual types of cancers is likely required for effective therapy. PMID:25374920

  16. A change in nuclear pore complex composition regulates cell differentiation.

    Science.gov (United States)

    D'Angelo, Maximiliano A; Gomez-Cavazos, J Sebastian; Mei, Arianna; Lackner, Daniel H; Hetzer, Martin W

    2012-02-14

    Nuclear pore complexes (NPCs) are built from ∼30 different proteins called nucleoporins or Nups. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation. The transmembrane nucleoporin Nup210 is absent in proliferating myoblasts and embryonic stem cells (ESCs) but becomes expressed and incorporated into NPCs during cell differentiation. Preventing Nup210 production by RNAi blocks myogenesis and the differentiation of ESCs into neuroprogenitors. We found that the addition of Nup210 to NPCs does not affect nuclear transport but is required for the induction of genes that are essential for cell differentiation. Our results identify a single change in NPC composition as an essential step in cell differentiation and establish a role for Nup210 in gene expression regulation and cell fate determination. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Germ cell nuclear factor regulates gametogenesis in developing gonads.

    Science.gov (United States)

    Sabour, Davood; Xu, Xueping; Chung, Arthur C K; Le Menuet, Damien; Ko, Kinarm; Tapia, Natalia; Araúzo-Bravo, Marcos J; Gentile, Luca; Greber, Boris; Hübner, Karin; Sebastiano, Vittorio; Wu, Guangming; Schöler, Hans R; Cooney, Austin J

    2014-01-01

    Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post-implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency-associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads.

  18. Legislation for the countermeasures on special issues of nuclear safety regulations

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Heon Jin; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

    2004-02-15

    Since the present nuclear safety regulation has some legal problems that refer to special issues and contents of regulatory provisions, this report has preformed research on the legal basic theory of nuclear safety regulation to solve the problems. In addition, this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation.

  19. Legislation for the countermeasures on special issues of nuclear safety regulations

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Hak Man; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

    2003-02-15

    Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.

  20. The European Union and nuclear safety; Die EU und die nukleare Sicherheit

    Energy Technology Data Exchange (ETDEWEB)

    Raetzke, Christian [CONLAR Consulting on Nuclear Law and Regulation, Leipzig (Germany)

    2014-02-15

    In recent years the EU Commission has developed a range of activities in the area of nuclear safety. Currently, the Commission has submitted a draft Directive revising the Nuclear Safety Directive 2009/71 to the Council. It seems that this draft text will undergo substantial changes in the course of Council deliberations and it is not clear yet whether any revision of the Directive will be adopted at all. The article shortly explains the background and the history of EU legislative activities in nuclear safety - a history which has been somewhat less than straightforward and has not yet reached its final chapter. The Commission's endeavours to introduce meaningful legislation have always met resistance from Member States determined to protect their sovereignty in this area. A decisive handicap for the Commission in this struggle certainly is the fact that it does not have a sufficient degree of in-house expertise in nuclear safety. Unless this is changed by upgrading and empowering the Commission to become a 'super-regulatory authority' - which seems to be very unlikely -, the Commission will have to resign itself to contribute to the further development of nuclear safety by closely cooperating with the Member States and their regulators. In any case, this can be a very effective and meaningful role. (orig.)

  1. Europe's progress towards joint regulation of nuclear safety; Le cheminement de l'Europe vers une reglementation commune sur la surete nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Hennenhofer, G. [surete des installations nucleaires et la radioprotection, Ministere de l' Environnement, de la Protection de la nature et de la securite nucleaire (BMU) (Germany)

    2010-11-15

    Following the end of the Second World War, there was great hope for the use of nuclear energy for peaceful applications. In the beginning, the different approaches adopted by East and West led to the design of different types of reactors, with priority being given to rapid development of the reactor fleet. Cooperation between safety regulators only came about very gradually. The Chernobyl disaster was in this respect the trigger event, as it clearly showed that the effects of nuclear events do not stop at borders and that collaboration by the safety regulators in this field was essential. Texts such as the Convention on Nuclear Safety, requiring the creation of a regulatory body independent of economic interests, the other work done by IAEA on the issue of nuclear safety and, within the European context, the creation of WENRA, are all milestones along the path to close cooperation. The recently adopted European directive on the safety of nuclear installations is the natural successor to these achievements. The road to a common European vision of nuclear safety is now mapped out. Germany will be joining this movement and making its own contribution. (author)

  2. Standard contract terms regulation in the proposal for a common European sales law

    NARCIS (Netherlands)

    Loos, M.B.M.

    2012-01-01

    In this paper, the regulation in standard contract terms in the proposal for a Commono European Sales Law (CESL) is compared with the regulation in the Unfair Terms Directive, the Draft Common Frame of Reference (DCFR) and the Vienna Sales Convention (CISG). The paper starts with an overview of the

  3. Emotion Regulation Strategies in European American and Hong Kong Chinese Middle School Children

    Science.gov (United States)

    Wan, Kayan Phoebe; Savina, Elena

    2016-01-01

    This study explored emotion regulation strategies in middle school European American (N = 54) and Hong Kong Chinese (N = 89) children. Children were presented with scenarios describing a fictitious girl/boy who encountered situations eliciting sadness, anger, and fear. Based on Gross' theory (1998), the survey of emotion regulation strategies was…

  4. Voluntary additional health insurance in the European union: Free market or regulation?

    NARCIS (Netherlands)

    P. Calcoen (Piet); W.P.M.M. van de Ven (Wynand)

    2017-01-01

    textabstractRecent European Court of Justice (ECJ) case law has highlighted apparent inconsistencies in ECJ rulings on the regulation of voluntary additional health insurance. In 2013, the ECJ upheld Belgian regulations limiting the operation of the free market by restricting increases in premium

  5. International and European atomic legislation. The military and civil use of nuclear energy from the view of international law and European law; Internationales und europaeisches Atomrecht. Die militaerische und friedliche Nutzung der Atomenergie aus Sicht des Voelker- und Europarechts

    Energy Technology Data Exchange (ETDEWEB)

    Odendahl, Kerstin (ed.) [Kiel Univ. (Germany). Professur fuer Oeffentliches Recht; Kiel Univ. (Germany). Walther-Schuecking-Inst. fuer Internationales Recht

    2013-07-01

    The book on the international and European atomic legislation covers the following issues: the military and civil use of nuclear energy from the view of international law and European law; the use of nuclear weapons in military conflicts; nuclear disarmament and the implementation of nuclear-free zones; the engagement against nuclear weapon proliferation; nuclear power plants from the view of international laws and the law concerning the respective interests of neighboring states; international cooperation in case of nuclear disasters - lessons learned from Chernobyl and Fukushima; the IAEA as the watchdog over the safety and peaceful use of nuclear energy? European legal requirements for the civil use of nuclear energy: EURATOM and EU norms.

  6. Nuclear exportin receptor CAS regulates the NPI-1-mediated nuclear import of HIV-1 Vpr.

    Directory of Open Access Journals (Sweden)

    Eri Takeda

    Full Text Available Vpr, an accessory protein of human immunodeficiency virus type 1, is a multifunctional protein that plays an important role in viral replication. We have previously shown that the region between residues 17 and 74 of Vpr (Vpr(N17C74 contained a bona fide nuclear localization signal and it is targeted Vpr(N17C74 to the nuclear envelope and then imported into the nucleus by importin α (Impα alone. The interaction between Impα and Vpr is important not only for the nuclear import of Vpr but also for HIV-1 replication in macrophages; however, it was unclear whether full-length Vpr enters the nucleus in a manner similar to Vpr(N17C74. This study investigated the nuclear import of full-length Vpr using the three typical Impα isoforms, Rch1, Qip1 and NPI-1, and revealed that full-length Vpr is selectively imported by NPI-1, but not Rch1 and Qip1, after it makes contact with the perinuclear region in digitonin-permeabilized cells. A binding assay using the three Impα isoforms showed that Vpr bound preferentially to the ninth armadillo repeat (ARM region (which is also essential for the binding of CAS, the export receptor for Impα in all three isoforms. Comparison of biochemical binding affinities between Vpr and the Impα isoforms using surface plasmon resonance analysis demonstrated almost identical values for the binding of Vpr to the full-length isoforms and to their C-terminal domains. By contrast, the data showed that, in the presence of CAS, Vpr was released from the Vpr/NPI-1 complex but was not released from Rch1 or Qip1. Finally, the NPI-1-mediated nuclear import of Vpr was greatly reduced in semi-intact CAS knocked-down cells and was recovered by the addition of exogenous CAS. This report is the first to show the requirement for and the regulation of CAS in the functioning of the Vpr-Impα complex.

  7. European experience of regulating distance selling of medicines for Ukraine.

    Science.gov (United States)

    Pashkov, Vitalii; Hrekov, Yevhen; Hrekova, Maryna

    Some countries have already tried and tested mechanisms of regulating distance sales as form of distribution of medicines that have been used more or less effectively for a fairly long time. Herewith, so far, the approach of the competent authorities of some countries including Ukraine can be called prevailing in quantitative terms under which the official prohibition on distance sales of medicines is set. The aim of this study is a detailed examination of the nature of the prohibition of the medicines distance selling in Ukraine, namely the an analysis of advantages and disadvantages of this form of distribution of medicines and identification of appropriate ways for gradual repeal of the prohibition in terms of regulatory reform in Ukraine in the sphere of circulation of medicines due to the process of adaptation of statutory regulation in this area to the EU legislation. This study is based on Ukrainian regulation acts, Council Directives 97/7/EC, 2000/31/EC, 2001/83/EC, scientific works and opinions of progressiveminded people in this sphere. Such methods as dialectical, comparative, analytic, synthetic and comprehensive have been used in the article. Reception of the described experience of regulation in EU will allow a further review of the principles of regulation in Ukraine in the sphere of medicines with a shift in the main emphasis in the direction of ensuring adequate consumer rights in this area and preventing the risks of patients' and public health.

  8. Medical Device Regulation: A Comparison of the United States and the European Union.

    Science.gov (United States)

    Maak, Travis G; Wylie, James D

    2016-08-01

    Medical device regulation is a controversial topic in both the United States and the European Union. Many physicians and innovators in the United States cite a restrictive US FDA regulatory process as the reason for earlier and more rapid clinical advances in Europe. The FDA approval process mandates that a device be proved efficacious compared with a control or be substantially equivalent to a predicate device, whereas the European Union approval process mandates that the device perform its intended function. Stringent, peer-reviewed safety data have not been reported. However, after recent high-profile device failures, political pressure in both the United States and the European Union has favored more restrictive approval processes. Substantial reforms of the European Union process within the next 5 to 10 years will result in a more stringent approach to device regulation, similar to that of the FDA. Changes in the FDA regulatory process have been suggested but are not imminent.

  9. The regulation of a project of the deregulation: UBER in Brazil and the European Union

    Directory of Open Access Journals (Sweden)

    Delphine Aurélie Laurence Defossez

    2017-04-01

    Full Text Available Purpose – This paper focuses on the regulation of Uber at regional level (Sao Paulo and Brasilia, national level (European Member States and supranational level (The European Commission initiative, which are often too restrictive. Methodology/approach/design – This article analyses standards and literature on regulation, as well as the role of competition. Attention was specially drawn to the market failure theory for justifying regulation, advocated by Breyer, Ogus and Baldwin & Cave. Due to the fact that there will be an evaluation of the regulations in place, consequentialism, welfarism and Pareto are briefly mentioned. Findings – None of the current regulatory responses, at the exception to Sao Paulo and the initiative by the European Commission that are not based exclusively on market failure theory, are working. Indeed, Uber is still banned in various cities. In others, the regulatory burden is so high that it takes away any incentives that Uber created. Regulation is not the only exit to market failure, competition must play a role. Uber is based on deregulation of the market and to try to regulate such concept with conventional theories will only lead to failures and restrictions. Practical implications – This article discusses the possible improvements to the already existing regulations. Originality/value – This paper correlates the regulation of Uber in Brazil and in Europe, explaining the difficulties these regulations are creating for Uber.

  10. Governmental policies and measures regulating nitrogen and phosphorus from animal manure in European Agriculture

    OpenAIRE

    Oenema, O.

    2005-01-01

    This paper discusses governmental policies and measures that regulate the use of animal manure in the European Union (EU-15). Systematic intervention by governments with European agriculture in general started at the end of the 19th century. Major changes in governmental policies on agriculture followed after the establishment of the EU and its Common Agricultural Policy (CAP) in 1957. Environmental side effects of the large-scale intensification of agricultural production were addressed foll...

  11. Overview of the principal european and french regulations on air, water and solid wastes

    Energy Technology Data Exchange (ETDEWEB)

    Piro, M.

    1995-12-31

    This paper summarises French and European regulation on discharges into the environment (excluding radio-active emissions), whether solid, liquid or gaseous, that is to say, covering solid wastes, aqueous effluents and atmospheric emissions. The report includes commentaries allowing a better understanding of the legislation. Three fields are examined: the air, solid wastes and water. For each sector, we have listed the European directives and their application in French law. The chronological order facilitates consultation. (author).

  12. DEMOCRITOS Demonstrators for Realization of Nuclear Electric Propulsion of the European Roadmaps MEGAHIT & DiPoP

    OpenAIRE

    Jansen, Frank; Bauer, Waldemar; Masson, Frederic; RUAULT, Jean-Marc; Worms, Jean-Claude; Detsis, Emmanouil; Lassoudiere, Francois; Granjon, Richard; Gaia, Enrico; Tosi, Martia Cristina; Semenkin, Alexander; Tinsley, Tim; Hodson, Zara; Koppel, Christophe

    2015-01-01

    The European Commission Horizon 2020 funded DEMOCRITOS project (2015-2017) will be primary focused to prepare preliminary design of the ground, core and space demonstrators and their test benches for the mega-watt class nuclear electric space propulsion INPPS flagship (International Nuclear Power and Propulsion System). In addition programmatic, organizational and funding aspects for international cooperation related to INPPS realization are sketched. The new project includes partners from Eu...

  13. Phytophthora ramorum and P. kernoviae: regulation in the European union

    Science.gov (United States)

    Stephen Hunter

    2008-01-01

    The history of the regulation of action against Phytophthora ramorum and P. kernoviae in the EU and U.K. is briefly summarised. For the former there are EU controls on the import of host plants, and the internal regime of plant passporting has been extended to cover Rhododendron, Viburnum and...

  14. The Nuclear Non-Proliferation Treaty: Regulating Nuclear Weapons around the World

    Science.gov (United States)

    Middleton, Tiffany Willey

    2010-01-01

    In May 2010, scientists, national security experts, and state delegates from nations around the world will convene in New York for the 2010 Nuclear Non-Proliferation Treaty Review Conference. They will review current guidelines for nuclear testing and possession of nuclear weapons in accordance with the Nuclear Non-Proliferation Treaty of 1968,…

  15. LODGEMENT OF FOREIGN CREDITORS’ CLAIMS ACCORDING TO THE EUROPEAN REGULATION ON INSOLVENCY PROCEEDINGS

    Directory of Open Access Journals (Sweden)

    Jasnica Garašić

    2016-01-01

    Full Text Available Rules of the European Regulation on insolvency proceedings regarding the right of foreign creditors to lodge their claims, the duty to inform foreign creditors on the opening of insolvency proceedings as well as the form, the content and the language of the lodgement of a claim of foreign creditors, that are contained in special Chapter IV of this Regulation, are analysed and evaluated in this paper. Furthermore, the paper examines the changes which are foreseen by the reformed European Regulation on insolvency proceedings of 2015 with regard to these rules and evaluates the adequacy of these changes considering difficulties which foreign creditors have in the practice when lodging their claims in insolvency proceedings that are opened in the Member States of the European Union.

  16. A possible biomedical facility at the European Organization for Nuclear Research (CERN).

    Science.gov (United States)

    Dosanjh, M; Jones, B; Myers, S

    2013-05-01

    A well-attended meeting, called "Brainstorming discussion for a possible biomedical facility at CERN", was held by the European Organization for Nuclear Research (CERN) at the European Laboratory for Particle Physics on 25 June 2012. This was concerned with adapting an existing, but little used, 78-m circumference CERN synchrotron to deliver a wide range of ion species, preferably from protons to at least neon ions, with beam specifications that match existing clinical facilities. The potential extensive research portfolio discussed included beam ballistics in humanoid phantoms, advanced dosimetry, remote imaging techniques and technical developments in beam delivery, including gantry design. In addition, a modern laboratory for biomedical characterisation of these beams would allow important radiobiological studies, such as relative biological effectiveness, in a dedicated facility with standardisation of experimental conditions and biological end points. A control photon and electron beam would be required nearby for relative biological effectiveness comparisons. Research beam time availability would far exceed that at other facilities throughout the world. This would allow more rapid progress in several biomedical areas, such as in charged hadron therapy of cancer, radioisotope production and radioprotection. The ethos of CERN, in terms of open access, peer-reviewed projects and governance has been so successful for High Energy Physics that application of the same to biomedicine would attract high-quality research, with possible contributions from Europe and beyond, along with potential new funding streams.

  17. The European Research on Severe Accidents in Generation-II and -III Nuclear Power Plants

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Van Dorsselaere

    2012-01-01

    Full Text Available Forty-three organisations from 22 countries network their capacities of research in SARNET (Severe Accident Research NETwork of excellence to resolve the most important remaining uncertainties and safety issues on severe accidents in existing and future water-cooled nuclear power plants (NPP. After a first project in the 6th Framework Programme (FP6 of the European Commission, the SARNET2 project, coordinated by IRSN, started in April 2009 for 4 years in the FP7 frame. After 2,5 years, some main outcomes of joint research (modelling and experiments by the network members on the highest priority issues are presented: in-vessel degraded core coolability, molten-corium-concrete-interaction, containment phenomena (water spray, hydrogen combustion…, source term issues (mainly iodine behaviour. The ASTEC integral computer code, jointly developed by IRSN and GRS to predict the NPP SA behaviour, capitalizes in terms of models the knowledge produced in the network: a few validation results are presented. For dissemination of knowledge, an educational 1-week course was organized for young researchers or students in January 2011, and a two-day course is planned mid-2012 for senior staff. Mobility of young researchers or students between the European partners is being promoted. The ERMSAR conference is becoming the major worldwide conference on SA research.

  18. Study on Economic Regulation of Collaborative Strategies among Container Shipping Companies Following Repeal of European Union Regulation 4056/86

    Directory of Open Access Journals (Sweden)

    Rawindaran Nair

    2016-06-01

    Full Text Available The European Union removed the block exemption granted under Regulation 4056/86, to liner shipping companies to provide scheduled services on a collaborative basis effective October 2008. This has also been followed by the proposed P3 alliance with participation of Maersk, MSC and CMA CGM. This paper explores, the arguments adopted by the US Federal Maritime Commission, the European Commission and the Ministry of Commerce of China, in rejecting the case proposed by the P3 alliance. The findings of this paper will inform on understanding strategies adopted by major Competition Regulatory authorities in their interpretation of horizontal collaboration in the industry.

  19. Resistive plate chamber online data quality monitoring for the Compact Muon Solenoid at the European Center for Nuclear Research

    CERN Document Server

    Whitaker, William David

    2008-01-01

    A comprehensive, online, data quality monitoring software package has been developed for the muon system at the European Center for Nuclear Research's (CERN's) Compact Muon Solenoid (CMS) experiment. The package was written in Java, C++, and HTML. It provides real-time, RPC performance feedback in an easy to use graphic user interface (GUI).

  20. Guidelines for direct radionuclide cystography; Empfehlungen zur Durchfuehrung der direkten Radionuklid-Zystographie bei Kindern. Richtlinie uebernommen vom Paediatric Committee der European Association of Nuclear Medicine (EANM)

    Energy Technology Data Exchange (ETDEWEB)

    Fettich, J. [Univ. Medical Centre Ljubljana (Slovenia); Colarinha, P. [Inst. Portugues de Oncologia, Lisboa (Portugal); Fischer, S.; Hahn, K.; Porn, U. [Klinik fuer Nuklearmedizin, LMU Muenchen (Germany); Froekier, J. [Aarhus Univ. Hospital - Skejby (Denmark); Gordon, I. [Great Ormond Street Hospital for Children, London (United Kingdom); Kabasakal, L. [Cerraphasa Tip Fakultesi, Nukleer Tip Ana Bilim Dali, Aksaray (Turkey); Mann, M. [Inst. of Child Health, Rondebosh, Red Cross Hospital, Capetown (South Africa); Mitjavila, M. [Hospital Universitario de Getafe, Madrid (Spain); Olivier, P. [CHU Nancy (France); Piepsz, A. [CHU St Pierre (Belgium); Roca, I. [Hospital Vall d' Hebron, Barcelona (Spain); Sixt, R. [The Queen Silvia Children' s Hospital, Goeteborg (Sweden); Velzen, J. van [ARPES (Netherlands)

    2002-07-01

    These ''Empfehlungen'' are the german translation of the Guidelines on MIBG-Scintigraphy in Children, which were published by the Paediatric Committee of the European Association of Nuclear Medicine. (orig.) [German] Bei den vorliegenden Empfehlungen handelt es sich um die deutsche Uebersetzung der vom Paediatric Committee der European Association of Nuclear Medicine (EANM) publizierten Guidelines. (orig.)

  1. Guidelines for MIBG-scintigraphy in children; Empfehlungen zur Durchfuehrung der MIBG-Szintigraphie bei Kindern. Leitlinie uebernommen vom Paediatric Committee der European Association of Nuclear Medicine (EANM)

    Energy Technology Data Exchange (ETDEWEB)

    Olivier, P. [CHU Nancy (France); Colarinha, P. [Inst. Portugues de Oncologia, Lisbon (Portugal); Fettich, J. [Univ. Medical Centre Ljubljana (Slovenia); Fischer, S.; Hahn, K.; Porn, U. [Klinik fuer Nuklearmedizin, Univ. of Munich (Germany); Froekier, J. [Aarhus Univ. Hospital - Skejby (Denmark); Giammarile, F. [Centre Leon Berard, Lyon (France); Gordon, I. [Great Ormond Street Hospital for Children, London (United Kingdom); Kabasakal, L. [Cerraphasa Tipp Fakultesi, Nukleer Tipp Ana Bilim Dali, Aksaray (Turkey); Mann, M. [Red Cross Hospital Cape Town (South Africa); Mitjavila, M. [Hospital Universitario de Getafe, Madrid (Spain); Piepsz, A. [AZ VUB and CHU St Pierre, Brussels (Belgium); Sixt, R. [Sahlgrenska Univ. Hospital Oestra, Goeteborg (Sweden); Velzen, J. van [ARPES (Netherlands)

    2002-07-01

    These ''Empfehlungen'' are the german translation of the Guidelines on MIBG-Scintigraphy in Children, which were published by the Paediatric Committee of the European Association of Nuclear Medicine. (orig.) [German] Bei den vorliegenden Empfehlungen handelt es sich um die deutsche Uebersetzung der vom Paediatric Committee der European Association of Nuclear Medicine (EANM) publizierten Guidelines. (orig.)

  2. Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries.

    Science.gov (United States)

    Lindner, Oliver; Pascual, Thomas N B; Mercuri, Mathew; Acampa, Wanda; Burchert, Wolfgang; Flotats, Albert; Kaufmann, Philipp A; Kitsiou, Anastasia; Knuuti, Juhani; Underwood, S Richard; Vitola, João V; Mahmarian, John J; Karthikeyan, Ganesan; Better, Nathan; Rehani, Madan M; Kashyap, Ravi; Dondi, Maurizio; Paez, Diana; Einstein, Andrew J

    2016-04-01

    Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 - 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest-of-the-world (RoW). Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 ± 3.4 mSv (RoW 11.4 ± 4.3 mSv; P cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in relation to the best practice quality score. A possible reason for the differences between Europe and the RoW could be the safety culture fostered by actions under the Euratom directives and the implementation of diagnostic reference levels. Stress-only imaging and weight-adjusted activity might be targets for optimization of European nuclear cardiology practice.

  3. Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries

    Energy Technology Data Exchange (ETDEWEB)

    Lindner, Oliver; Burchert, Wolfgang [University Hospital of the Ruhr University, Institute of Radiology, Nuclear Medicine and Molecular Imaging, Heart and Diabetes Center North Rhine-Westphalia Bochum, Bad Oeynhausen (Germany); Pascual, Thomas N.B.; Kashyap, Ravi; Dondi, Maurizio; Paez, Diana [International Atomic Energy Agency, Section of Nuclear Medicine and Diagnostic Imaging, Division of Human Health, Vienna (Austria); Mercuri, Mathew [Columbia University Medical Center and New York-Presbyterian Hospital, Division of Cardiology, Department of Medicine, New York, NY (United States); Acampa, Wanda [National Council of Research, Institute of Biostructures and Bioimaging, Naples (Italy); Flotats, Albert [Universitat Autonoma de Barcelona, Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Kaufmann, Philipp A. [University Hospital Zurich, Department of Nuclear Medicine and Cardiac Imaging, Zurich (Switzerland); Kitsiou, Anastasia [Sismanoglio Hospital, Department of Cardiology, Athens (Greece); Knuuti, Juhani [University of Turku, and Turku University Hospital, Turku PET Centre, Turku (Finland); Underwood, S.R. [Imperial College London, National Heart and Lung Institute, London (United Kingdom); Royal Brompton and Harefield Hospitals, Department of Nuclear Medicine, London (United Kingdom); Vitola, Joao V. [Quanta Diagnostico and Terapia, Curitiba (Brazil); Mahmarian, John J. [Houston Methodist DeBakey Heart and Vascular Center, Department of Cardiology, Houston, TX (United States); Karthikeyan, Ganesan [All India Institute of Medical Sciences, Department of Cardiology, New Delhi (India); Better, Nathan [Royal Melbourne Hospital and University of Melbourne, Department of Nuclear Medicine, Melbourne (Australia); Rehani, Madan M. [International Atomic Energy Agency, Radiation Protection of Patients Unit, Vienna (Austria); Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Einstein, Andrew J. [Columbia University Medical Center and New York-Presbyterian Hospital, Division of Cardiology, Department of Medicine, New York, NY (United States); Columbia University Medical Center and New York-Presbyterian Hospital, Department of Radiology, New York, NY (United States); Collaboration: for the INCAPS Investigators Group

    2016-04-15

    Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 - 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest-of-the-world (RoW). Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 ± 3.4 mSv (RoW 11.4 ± 4.3 mSv; P < 0.001) and of PET was 2.6 ± 1.5 mSv (RoW 3.8 ± 2.5 mSv; P < 0.001). The mean effective doses of SPECT and PET differed between European regions (P < 0.001 and P = 0.002, respectively). The mean quality score was 6.2 ± 1.2, which was higher than the RoW score (5.0 ± 1.1; P < 0.001). Adherence to best practices did not differ significantly among the European regions (range 6 to 6.4; P = 0.73). Of the best practices, stress-only imaging and weight-adjusted dosing were the least commonly used. In Europe, the mean effective dose from nuclear cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in

  4. Nuclear-cytoplasmic trafficking of NTF2, the nuclear import receptor for the RanGTPase, is subjected to regulation.

    Directory of Open Access Journals (Sweden)

    Shawn C Chafe

    Full Text Available NTF2 is a cytosolic protein responsible for nuclear import of Ran, a small Ras-like GTPase involved in a number of critical cellular processes, including cell cycle regulation, chromatin organization during mitosis, reformation of the nuclear envelope following mitosis, and controlling the directionality of nucleocytoplasmic transport. Herein, we provide evidence for the first time that translocation of the mammalian NTF2 from the nucleus to the cytoplasm to collect Ran in the GDP form is subjected to regulation. Treatment of mammalian cells with polysorbitan monolaurate was found to inhibit nuclear export of tRNA and proteins, which are processes dependent on RanGTP in the nucleus, but not nuclear import of proteins. Inhibition of the export processes by polysorbitan monolaurate is specific and reversible, and is caused by accumulation of Ran in the cytoplasm because of a block in translocation of NTF2 to the cytoplasm. Nuclear import of Ran and the nuclear export processes are restored in polysorbitan monolaurate treated cells overproducing NTF2. Moreover, increased phosphorylation of a phospho-tyrosine protein and several phospho-threonine proteins was observed in polysorbitan monolaurate treated cells. Collectively, these findings suggest that nucleocytoplasmic translocation of NTF2 is regulated in mammalian cells, and may involve a tyrosine and/or threonine kinase-dependent signal transduction mechanism(s.

  5. Safety regulations of fuzzy-logic control to nuclear reactors

    OpenAIRE

    Ruan, Da

    2000-01-01

    We present an R&D project on fuzzy-logic control applications to the Belgian Nuclear Reactor 1 (BR1) at the Belgian Nuclear Research Centre (SCK•CEN). The project started in 1995 and aimed at investigating the added value of fuzzy logic control for nuclear reactors. We first review some relevant literature on fuzzy logic control in nuclear reactors, then present the state-of-the-art of the BR1 project, with an understanding of the safety requirements for this real fuzzy-logic control ...

  6. Investing in Health and Market Regulation in the European Health Care System

    OpenAIRE

    Shipkovenska, Elena; Vodenicharov, Tzekomir; Dyakova, Mariana

    2008-01-01

    The authors analyze the basic financial principles and the regulated entrepreneurship in the healthcare systems in Europe. They point out that the European countries organize, manage and finance their health care in different ways. Thus the health systems vary not only in the financial methods used, but also in the payment scheme of the insurance institution and the healthcare providers as well as the ways in which the state regulates the health services provision and the development of marke...

  7. War of the worlds? : Pluralism vs. market liberalisation: the European regulation of the television broadcasting sector

    OpenAIRE

    Komorek, Ewa

    2008-01-01

    This thesis makes the case for the European regulation of media concentration in the television broadcasting sector. Television broadcasting is currently undergoing substantial and rapid changes. The phenomena of digitalisation and the resulting technological convergence stimulate the minds of regulators in Europe and underlie the new Audiovisual Services Directive which is to replace the Television Without Frontiers Directive. There is even a trend to proclaim the death of television broadca...

  8. Economic valuation of the mortality benefits of a regulation on SO2 in 20 European cities.

    Science.gov (United States)

    Chanel, Olivier; Henschel, Susann; Goodman, Patrick G; Analitis, Antonis; Atkinson, Richard W; Le Tertre, Alain; Zeka, Ariana; Medina, Sylvia

    2014-08-01

    Since the 1970s, legislation has led to progress in tackling several air pollutants. We quantify the annual monetary benefits resulting from reductions in mortality from the year 2000 onwards following the implementation of three European Commission regulations to reduce the sulphur content in liquid fuels for vehicles. We first compute premature deaths attributable to these implementations for 20 European cities in the Aphekom project by using a two-stage health impact assessment method. We then justify our choice to only consider mortality effects as short-term effects. We rely on European studies when selecting the central value of a life-year estimate (€ 2005 86 600) used to compute the monetary benefits for each of the cities. We also conduct an independent sensitivity analysis as well as an integrated uncertainty analysis that simultaneously accounts for uncertainties concerning epidemiology and economic valuation. The implementation of these regulations is estimated to have postponed 2212 (95% confidence interval: 772-3663) deaths per year attributable to reductions in sulphur dioxide for the 20 European cities, from the year 2000 onwards. We obtained annual mortality benefits related to the implementation of the European regulation on sulphur dioxide of € 2005 191.6 million (95% confidence interval: € 2005 66.9-€ 2005 317.2). Our approach is conservative in restricting to mortality effects and to short-term benefits only, thus only providing the lower-bound estimate. Our findings underline the health and monetary benefits to be obtained from implementing effective European policies on air pollution and ensuring compliance with them over time. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  9. A review of pesticide policies and regulations for urban amenity areas in seven European countries

    NARCIS (Netherlands)

    Kristoffersen, P.; Rask, A.M.; Grundy, A.; Franzen, I.; Kempenaar, C.; Raisio, J.; Schroeder, H.; Spijker, J.H.; Verschwele, A.; Zarina, L.

    2008-01-01

    An analysis of the regulations of herbicide use for weed control in non-agricultural/urban amenity areas, including actual pesticide use, was carried out as a joint survey of seven European countries: Denmark, Finland, Germany, Latvia, the Netherlands, Sweden and United Kingdom. Herbicides

  10. The meta-governance of organic seed regulation in the USA, European Union and Mexico

    NARCIS (Netherlands)

    Renaud, Erica; Lammerts van Bueren, Edith; Jiggins, Janice

    2016-01-01

    Seed governance in agriculture is a challenging global issue. This paper analyses the evolution of organic seed regulation in the USA, the European Union and Mexico as model cases of how these challenges are being addressed, based on a study conducted between 2007 and 2014. It highlights how

  11. European regulation affecting nanomaterials – review of limitations and future recommendations

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Baun, Anders

    2012-01-01

    regulation in regard to nanomaterials is a starting point in a democratic and transparent process towards adapting existing laws and facilitating an informed discussion about which kind of regulatory options best address the identified limitations. In the following we will introduce key pieces of European...

  12. The changes in hazard classification and product notification procedures of the new European CLP and Cosmetics Regulations

    NARCIS (Netherlands)

    de Groot, Ronald; Brekelmans, Pieter; Herremans, Joke; Meulenbelt, Jan

    Introduction. The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN-GHS) is developed to harmonize the criteria for hazard communication worldwide. The European Regulation on classification, labeling, and packaging of substances and mixtures [CLP Regulation

  13. The changes in hazard classification and product notification procedures of the new European CLP and Cosmetics Regulations.

    NARCIS (Netherlands)

    de Groot, R.; Brekelmans, P.; Herremans, J.; Meulenbelt, J.|info:eu-repo/dai/nl/079479227

    2010-01-01

    INTRODUCTION: The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN-GHS) is developed to harmonize the criteria for hazard communication worldwide. The European Regulation on classification, labeling, and packaging of substances and mixtures [CLP Regulation

  14. Establishment and Analysis of Nuclear Structure Data DB for Nuclear Safety Regulation Technique Applications

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Ouk; Yoo, Jae Kwon; Gil, Choong; Cho, Young Sik; Kim, Hyung Il; Kim, Jong Woon; Kwon, Duk Hee; Lee, Jong Hwa

    2013-10-15

    The contents of the project consisting of four research fields carried out are: Ο Installation of DB with nuclear structure/decay datasets - Setup a computer system for production of nuclear structure/decay data in ENSDF format - Production of nuclear structure/decay data in ENSDF format({sup 211}, {sup 215}Po, {sup 136}Cs) and setup a data converting system from ENSDF format to ENDF-6 format. Ο Computer simulation of nuclear decay and burnup using the ENSDF DB - Calculation of decay heats of the several radioactive nuclides with Geant4 - Burnup calculation with full decay chain using Monte Carlo method Ο Comparison and analysis of nuclear structure/decay and fission product yields data. - Acquisitions and Analyses of decay and fission yields data in ENDF-6 format - Research for theoretical evaluation method of fission product yields data. Ο Analysis of SCALE(ORIGEN-s, -ARP) libraries - Analysis of ORIGEN library structure of nuclear decay/yields data. - Methodological studies to improve nuclear decay/yield ORIGEN libraries by use of nuclear structure/yield data in ENDF-6 format. The results of this project will be a basis to establish the nuclear decay and fission yield data DB in Korea. Additionally, new decay and yield data can be immediately served for the users to utilize those data for nuclear research and/or development.

  15. Comparison between regulations in different European countries; Comparaison des reglementations dans les differents pays d`Europe

    Energy Technology Data Exchange (ETDEWEB)

    Cottard, E. [Cogen Europe (France)

    1997-12-31

    This paper analyzes the different European regulations about atmospheric pollutant emissions (NO{sub x}, CO, CO{sub 2}, SO{sub 2}) and with respect to cogeneration systems (gas turbines and engines). The European, German, Danish, Dutch, Italian, UK and OECD regulations are compared. (J.S.)

  16. Driving a CERN vehicle in the European Union: new customs regulation

    CERN Document Server

    2015-01-01

    On 1 May 2015, the European Union brought in a new regulation regarding “the temporary importation of means of transport intended to be used by a natural person resident in the customs territory of the Union” (see here).   This regulation also applies to vehicles belonging to or rented by CERN, but does not necessitate any modifications to the provisions of Operational Circular No. 4 regarding the use of these vehicles. The Direction régionale des douanes du Léman (Léman regional customs directorate) has informed the Organization that members of the CERN personnel and contractors' personnel may present their CERN access card instead of the contract of employment specified in the European regulation in the event of inspection by the customs authorities. In this context, we would like to remind you of the following provisions of Operational Circular No. 4: Paragraph 10 (“Use of vehicles for private purposes (e.g. for transpor...

  17. Actualization of the Brazilian nuclear regulations; Atualizacao das normas nucleares brasileiras

    Energy Technology Data Exchange (ETDEWEB)

    Wieland, Patricia; Soares, Abner Duarte; Nogueira, Tindyua de Moraes; Monteiro, Iara Arraes; Pitta, Maria Adelia Rocha; Bruno, Natanael Carvalho; Pereira, Enneite Souza; Pinto, Marvio dos S.; Lidington, Regina Marcia Rocha; Rocha, Marco Aurelio Toledo, E-mail: pwieland@cnen.gov.b, E-mail: asoares@cnen.gov.b, E-mail: tnogueira@cnen.gov.b, E-mail: iara@cnen.gov.b, E-mail: mpitta@cnen.gov.b, E-mail: nbruno@cnen.gov.b, E-mail: espereira@cnen.gov.b, E-mail: marvio@cnen.gov.b, E-mail: , E-mail: rmliding@cnen.gov.b, E-mail: mtoledo@cnen.gov.b [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Div. de Normas

    2011-10-26

    The present work has the objective of making public the methodological approach adopted by the Brazilian Nuclear Energy Commission (CNEN) to create a nuclear normative structure up-dated and coherent. According to the Law 4118/62, 6189/74 and 7781/89, is the attribution the CNEN to establish specific guidelines for nuclear safety and radiological protection, and also do dictate safety norms through the emission of Resolutions

  18. [Regulation of food supplements in the European Union and its member states. Part I].

    Science.gov (United States)

    Petrenko, A S; Ponomareva, M N; Sukhanov, B P

    2014-01-01

    The article discusses aspects of the regional (the European Union) and national (European countries) regulation of food supplements. The definition of the supplement category is given. The contemporary issues of nutrition in developed countries are discussed, and the essential role of food supplements in the diet is emphasized. In particular, the use of vitamins, minerals, botanicals and their chemical constituents in food supplements as well as the issue of setting maximum daily limits are discussed. The positive lists of vitamins, minerals and their chemical modifications are presented. The paper also outlines aspects of supplement safety, requirements for their labelling and pre-market notification procedure.

  19. [Regulation of food supplements in the European Union and its member states. Part 2].

    Science.gov (United States)

    Petrenko, A S; Ponomareva, M N; Sukhanov, B P

    2014-01-01

    The article discusses various aspects of the regional (the European Union) and national (European countries) regulation related to food supplements. The use of botanicals and minor bioactive substances in food supplements, and their labelling are studied. The EU principle of mutual recognition is described in the context of current challenges that exist in the regulatory harmonisation between the EU member states. The concept of novel foods and novel ingredients is also presented, and the procedure of their pre-market approval is described in detail. Basic principles of using claims for food supplements are also outlined.

  20. Studies in nuclear receptor Nurr1 : Identification of Nurr1-regulated genes

    OpenAIRE

    Hermanson, Elisabet

    2004-01-01

    The nuclear receptor family comprises more than sixty members, including receptors for steroids, thyroid hormone and retinoids. Many nuclear receptors function as ligand- activated transcription factors that regulate the expression of specific target genes. The family also includes nuclear receptors that lack identified ligands, and these receptors are therefore referred to as orphan receptors. It has recently been shown that some of these orphan receptors are ligand- indepe...

  1. The nuclear import of ribosomal proteins is regulated by mTOR

    Science.gov (United States)

    Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

    2014-01-01

    Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

  2. Ethical and legal framework and regulation for off-label use: European perspective.

    Science.gov (United States)

    Lenk, Christian; Duttge, Gunnar

    2014-01-01

    For more than 20 years the off-label use of drugs has been an essential part of the ethical and legal considerations regarding the international regulation of drug licensing. Despite a number of regulatory initiatives in the European Union, there seems to remain a largely unsatisfactory situation following a number of critical descriptions and statements from actors in the field. The present article gives an overview of the ethical and legal framework and developments in European countries and identifies existing problems and possible pathways for solutions in this important regulatory area. In addition to the presentation of the ethical and legal foundations, some attention is given to criticisms from medical practitioners to the current handling of off-label drug use. The review also focuses on the situation confronted by patients and physicians when off-label prescriptions are necessary. Through legal descriptions from a number of countries, possible solutions for future discussion of European health care policy are selected and explained.

  3. Regulating private human suborbital flight at the international and European level: Tendencies and suggestions

    Science.gov (United States)

    Masson-Zwaan, Tanja; Moro-Aguilar, Rafael

    2013-12-01

    In the context of the FAST20XX project (Future High-Altitude High-Speed Transport) that started in 2009 under the 7th Framework Programme of the European Union (EU), the authors reexamined the legal status of private human suborbital flight, and researched whether it might be regulated as aviation or as spaceflight. International space law is ambiguous as to accommodating suborbital activities. While some provisions of the UN outer space treaties would seem to exclude them, generally there is not any explicit condition in terms of reaching orbit as a requirement for application. International air law presents equal difficulties in dealing with this activity. The classic definition of "aircraft" as contained in the Annexes to the Chicago Convention does not really encompass the kind of rocket-powered vehicles that are envisaged here. As a result, it is unclear whether the United Nations Committee on the Peaceful Uses of Outer Space (COPUOS), the International Civil Aviation Organization (ICAO), or both could be involved in an eventual international regulation of suborbital flight. In the absence of a uniform international regime, each state has the sovereign right to regulate human suborbital flights operating within its airspace. So far, two practical solutions have been realised or proposed, and will be analyzed. On the one hand, the USA granted power for regulation and licensing over private human suborbital flight to the Office of Commercial Space Transportation of the Federal Aviation Administration (FAA/AST). Subsequent regulations by the FAA have set out a series of requirements for companies that want to operate these flights, enabling a market to develop. On the other side of the Atlantic, both the European Space Agency (ESA) and a group of representatives of the European Aviation Safety Agency (EASA) of the European Union (EU) seem to rather regard this activity as aviation, potentially subject to the regulation and certification competences of EASA

  4. The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly

    Science.gov (United States)

    Riolobos, Laura; Domínguez, Carlos; Kann, Michael; Almendral, José M.

    2015-01-01

    It is unknown whether the mammalian cell cycle could impact the assembly of viruses maturing in the nucleus. We addressed this question using MVM, a reference member of the icosahedral ssDNA nuclear parvoviruses, which requires cell proliferation to infect by mechanisms partly understood. Constitutively expressed MVM capsid subunits (VPs) accumulated in the cytoplasm of mouse and human fibroblasts synchronized at G0, G1, and G1/S transition. Upon arrest release, VPs translocated to the nucleus as cells entered S phase, at efficiencies relying on cell origin and arrest method, and immediately assembled into capsids. In synchronously infected cells, the consecutive virus life cycle steps (gene expression, proteins nuclear translocation, capsid assembly, genome replication and encapsidation) proceeded tightly coupled to cell cycle progression from G0/G1 through S into G2 phase. However, a DNA synthesis stress caused by thymidine irreversibly disrupted virus life cycle, as VPs became increasingly retained in the cytoplasm hours post-stress, forming empty capsids in mouse fibroblasts, thereby impairing encapsidation of the nuclear viral DNA replicative intermediates. Synchronously infected cells subjected to density-arrest signals while traversing early S phase also blocked VPs transport, resulting in a similar misplaced cytoplasmic capsid assembly in mouse fibroblasts. In contrast, thymidine and density arrest signals deregulating virus assembly neither perturbed nuclear translocation of the NS1 protein nor viral genome replication occurring under S/G2 cycle arrest. An underlying mechanism of cell cycle control was identified in the nuclear translocation of phosphorylated VPs trimeric assembly intermediates, which accessed a non-conserved route distinct from the importin α2/β1 and transportin pathways. The exquisite cell cycle-dependence of parvovirus nuclear capsid assembly conforms a novel paradigm of time and functional coupling between cellular and virus life

  5. Concurring Regulation in European Forest Law; Forest Certification and the New EU Timber Regulation

    NARCIS (Netherlands)

    Kistenkas, F.H.

    2013-01-01

    Newly made EU Timber Regulation (EUTR) may prima facie look like competing regulation and an overlap of the existing forest certification schemes of FSC and PEFC as also EUTR combats illegally harvested timber. The novel EUTR, however, is a public law scheme wheras FSC and PEFC are private law

  6. Reasons for Regulating Informal Relationships: A comparison of nine European jurisdictions

    Directory of Open Access Journals (Sweden)

    Charlotte Mol

    2016-07-01

    Full Text Available In Europe, informal relationships have been increasing in number. While the regulation of informal relationships is recent and relatively limited, nine European jurisdictions have taken legislative action and adopted a lex specialis for informal relationships. This article takes a comparative approach in order to answer the following questions: What were the incentives and reasons for the regulation of informal relationships in the family laws of nine European jurisdictions and are these reasons reflected in the legal definitions and effects? And if so, how? Using the most recent national reports of the Commission on European Family Law, the comparative analysis reveals five common reasons and incentives: (1 the steady increase of informal relationships, (2 the financial protection of a vulnerable party, (3 the influence of national Constitutions, (4 the recognition of same-sex couples and (5 the protection of the common child. The comparison also reveals that in spite of these shared reasons, there is great diversity in the legal definitions and effects in the nine European jurisdictions.

  7. Computational characterization of modes of transcriptional regulation of nuclear receptor genes.

    Science.gov (United States)

    Sharma, Yogita; Chilamakuri, Chandra Sekhar Reddy; Bakke, Marit; Lenhard, Boris

    2014-01-01

    Nuclear receptors are a large structural class of transcription factors that act with their co-regulators and repressors to maintain a variety of biological and physiological processes such as metabolism, development and reproduction. They are activated through the binding of small ligands, which can be replaced by drug molecules, making nuclear receptors promising drug targets. Transcriptional regulation of the genes that encode them is central to gaining a deeper understanding of the diversity of their biochemical and biophysical roles and their role in disease and therapy. Even though they share evolutionary history, nuclear receptor genes have fundamentally different expression patterns, ranging from ubiquitously expressed to tissue-specific and spatiotemporally complex. However, current understanding of regulation in nuclear receptor gene family is still nascent. In this study, we investigate the relationship between long-range regulation of nuclear receptor family and their known functionality. Towards this goal, we identify the nuclear receptor genes that are potential targets based on counts of highly conserved non-coding elements. We validate our results using publicly available expression (RNA-seq) and histone modification (ChIP-seq) data from the ENCODE project. We find that nuclear receptor genes involved in developmental roles show strong evidence of long-range mechanism of transcription regulation with distinct cis-regulatory content they feature clusters of highly conserved non-coding elements distributed in regions spanning several Megabases, long and multiple CpG islands, bivalent promoter marks and statistically significant higher enrichment of enhancer mark around their gene loci. On the other hand nuclear receptor genes that are involved in tissue-specific roles lack these features, having simple transcriptional controls and a greater variety of mechanisms for producing paralogs. We further examine the combinatorial patterns of histone maps

  8. Computational characterization of modes of transcriptional regulation of nuclear receptor genes.

    Directory of Open Access Journals (Sweden)

    Yogita Sharma

    Full Text Available Nuclear receptors are a large structural class of transcription factors that act with their co-regulators and repressors to maintain a variety of biological and physiological processes such as metabolism, development and reproduction. They are activated through the binding of small ligands, which can be replaced by drug molecules, making nuclear receptors promising drug targets. Transcriptional regulation of the genes that encode them is central to gaining a deeper understanding of the diversity of their biochemical and biophysical roles and their role in disease and therapy. Even though they share evolutionary history, nuclear receptor genes have fundamentally different expression patterns, ranging from ubiquitously expressed to tissue-specific and spatiotemporally complex. However, current understanding of regulation in nuclear receptor gene family is still nascent.In this study, we investigate the relationship between long-range regulation of nuclear receptor family and their known functionality. Towards this goal, we identify the nuclear receptor genes that are potential targets based on counts of highly conserved non-coding elements. We validate our results using publicly available expression (RNA-seq and histone modification (ChIP-seq data from the ENCODE project. We find that nuclear receptor genes involved in developmental roles show strong evidence of long-range mechanism of transcription regulation with distinct cis-regulatory content they feature clusters of highly conserved non-coding elements distributed in regions spanning several Megabases, long and multiple CpG islands, bivalent promoter marks and statistically significant higher enrichment of enhancer mark around their gene loci. On the other hand nuclear receptor genes that are involved in tissue-specific roles lack these features, having simple transcriptional controls and a greater variety of mechanisms for producing paralogs. We further examine the combinatorial patterns of

  9. Self-regulation and the new challenges in journalism: Comparative study across European countries

    Directory of Open Access Journals (Sweden)

    Matthias Karmasin

    2011-01-01

    Full Text Available The objective of this article is to compare the self-regulatory systems of the journalistic profession in Austria, Germany, Denmark, Estonia, Spain, France and Poland. Based on the analysis of the different cases and situations in these seven countries, we offer a comparative analysis of the existence of: ethical codes, pro-consumers associations, print and audiovisual press councils, level of organization and unionism among journalists. The results reveal deficiencies in the European systems as well as progressions in the implementation of self-regulation tools in the journalistic profession, mainly in the field of print and audiovisual media. In most European countries under study, online newspapers lack self-regulatory tools, except for the regulation coming from their parent print or broadcast media companies.

  10. Perspectives on CFD analysis in nuclear reactor regulation

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, Christopher, E-mail: christopher.boyd@nrc.gov

    2016-04-01

    The U.S. Nuclear Regulatory Commission is tasked with ensuring that the commercial use of nuclear materials in the United States is safe. This includes the review and evaluation of submitted analyses that support the safety justification for specific reactor-system components or scenarios. Typically these analyses involve the use of codes that have a proven history of validation and acceptance for the specific application of interest. The use of computational fluid dynamics (CFD) has not been as widespread in regulatory activities and the experience level with acceptance is more limited. The ever-increasing capacity of computers, along with the growing number of capable analysts, ensures us that CFD applications will continue to grow in usage for nuclear safety analysis. The challenge ahead is to ensure that these tools are properly validated and applied in order to build up the necessary evidence for more common acceptance in regulatory processes. The challenges include a continuation of the development and maintenance of best-practice guidance, development of problem-specific CFD-grade benchmark studies, the application of verification and validation techniques, and the development of practical treatments for uncertainties and scaling. Through these efforts, it is anticipated that CFD methods will continue to gain acceptance for use in nuclear reactor safety applications.

  11. Nuclear translocation contributes to regulation of DNA excision repair activities

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne

    2009-01-01

    .T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3-34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89-108]. Protein interactions are not only important for function, but also...

  12. European regulations for the introduction of novel radiopharmaceuticals in the clinical setting.

    Science.gov (United States)

    Decristoforo, Clemens; Penuelas, Ivan; Patt, Marianne; Todde, Sergio

    2017-06-01

    The development of novel radiopharmaceuticals is very rapid and highly innovative both for diagnostic and therapeutic applications. The translation into the clinic, however, is hampered by the high regulatory demands in Europe. This article describes the main rules, guidelines and guidance documents in the European Union in relation to the pharmaceutical regulatory framework. Until today a great number of radiopharmaceuticals are introduced clinically using specific national pathways outside the clinical trial regulation and examples are provided. In this context, the European Pharmacopoeia with a legal status plays an important role in defining quality standards. For clinical trials the application system and regulatory framework in Europe is currently considerably changing. Whereas the current clinical trial directive requires a lengthy and complicated national application process, the new regulation 536/2014 will introduce a streamlined and unified European application process. This new regulation also takes into account the specific properties of radioactive investigational medicinal products and has introduced exceptions for good manufacturing practices (GMP) and labelling for radiopharmaceuticals. Besides the main regulatory texts, several guidelines have been published, e.g. related to toxicity testing or first in man studies. In relation to radiopharmaceuticals professional organization, in particular the EANM, have published a number of documents in relation to GMP, documentation and toxicity studies, that support professionals in the application process. All these documents are summarized and discussed.

  13. Nuclear regulation: Public knowledge of radiological emergency procedures

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    GAO found that no federal agency assesses public knowledge of radiological emergency procedures. The Federal Emergency Management Agency has responsibility for ensuring the adequacy of offsite emergency plans at nuclear power plants and has periodically conducted surveys to determine whether emergency planning zones residents have received basic emergency planning information. However, FEMA has not assessed whether the public actually knows what to do in the event of an emergency. GAO believes it is appropriate that FEMA do this. This report provides information concerning the actions that utilities and FEMA take to notify EPZ residents of the procedures to be followed if a nuclear accident occurs. It recommends that FEMA develop a survey to assess EPZ residents' knowledge of radiological emergency procedures.

  14. Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

    Directory of Open Access Journals (Sweden)

    Marriott Susan J

    2007-12-01

    Full Text Available Abstract Background The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS. We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins. Results We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284 within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35. Conclusion This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284

  15. Inconsistencies among European Union pharmaceutical regulator safety communications: a cross-country comparison.

    Directory of Open Access Journals (Sweden)

    Jean-David Zeitoun

    Full Text Available The European Medicines Agency (EMA and national regulators share the responsibility to communicate to healthcare providers postmarketing safety events but little is known about the consistency of this process. We aimed to compare public availability of safety-related communications and drug withdrawals from the EMA and European Union member countries for novel medicines.We performed a cross-sectional analysis using public Dear Healthcare Professional Communications (DHPCs for all novel medicines authorized between 2001 and 2010 by the EMA and available for use in France, Netherlands, Spain, and the United Kingdom. Between 2001 and 2010, the EMA approved 185 novel medicines. DHPCs could not be ascertained for the EMA. Among the 4 national regulators, as of April 30, 2013, at least one safety DHPC or withdrawal occurred for 53 (28.6% medicines, totaling 90 DHPCs and 5 withdrawals. Among these 53 medicines, all 4 national agencies issued at least one communication for 17 (32.1%, three of the four for 25 (47.2%, two of the four for 6 (11.3%, and one of the four for 5 (9.4%. Five drugs were reported to be withdrawn, three by all four countries, one by three and one by two. Among the 95 DHPCs and withdrawals, 20 (21.1% were issued by all 4 national regulators, 37 (38.9% by 3 of the 4, 22 (23.2% by 2 of the 4, and 16 (16.8% by one. Consistency of making publicly available all identified safety DHPC or withdrawal across regulator pairs varied from 33% to 73% agreement.Safety communications were not made publicly available by the EMA. Among the 4 European member countries with national regulators that make DHPCs publicly available since at least 2001, there were substantial inconsistencies in safety communications for novel medicines. The impact of those inconsistencies in terms of public health remains to be determined.

  16. The plant nuclear envelope and regulation of gene expression.

    Science.gov (United States)

    Parry, Geraint

    2015-03-01

    The nuclear envelope (NE) separates the key mechanisms of transcription and translation, and as such is a critical control point in all eukaryotic cells. In plants, the proteins of the NE influence a number of processes including the control of nucleo-cytoplasmic transport of RNA and protein, chromatin localization to the nuclear periphery, and direct chromatin binding by members of the nuclear pore complex (NPC). In this review I attempt to bring these roles under the umbrella of their effect on gene expression, even though the complex nature of this cellular environment means there is considerable overlap of effects. Although the volume of research in plant cells has greatly improved over recent years, it is clear that our understanding of how the components of the NE either directly or indirectly influence gene expression is still in its infancy. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Cofilin Regulates Nuclear Architecture through a Myosin-II Dependent Mechanotransduction Module

    Science.gov (United States)

    Wiggan, O’Neil; Schroder, Bryce; Krapf, Diego; Bamburg, James R.; DeLuca, Jennifer G.

    2017-01-01

    Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking. Here we identify that Cofilin/ADF-family F-actin remodeling proteins are essential for normal nuclear structure in different cell types. siRNA mediated silencing of Cofilin/ADF provokes striking nuclear defects including aberrant shapes, nuclear lamina disruption and reductions to peripheral heterochromatin. We provide evidence that these anomalies are primarily due to Rho kinase (ROCK) controlled excessive contractile myosin-II activity and not to elevated F-actin polymerization. Furthermore, we demonstrate a requirement for nuclear envelope LINC (linker of nucleoskeleton and cytoskeleton) complex proteins together with lamin A/C for nuclear aberrations induced by Cofilin/ADF loss. Our study elucidates a pivotal regulatory mechanism responsible for normal nuclear structure and which is expected to fundamentally influence nuclear function. PMID:28102353

  18. Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr

    2014-07-18

    Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.

  19. The experience on public consultation in the elaboration of nuclear regulations

    Energy Technology Data Exchange (ETDEWEB)

    Monteiro, Iara A.; Pitta, Maria Adelia R.; Pereira, Enneite S.; Wieland, Patricia [Comissao Nacional e Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil)], e-mail: iara@cnen.gov.br

    2009-07-01

    This paper presents and discusses the process of public consultation followed by the regulatory body, Nuclear Energy National Commission (CNEN), during the elaboration of nuclear regulations. In this paper, the due legislation on federal administration, law n. 9784/99, is referred to and the procedures established by CNEN for the elaboration of a nuclear regulation are described. The public consultation has the objective of improving the democratization of nuclear regulations elaboration process, allowing the participation of interested parties such as professional associations directly involved, organizations interested in its application and the general public. During the process of elaboration of a nuclear regulation, the basic text is, first of all, discussed and improved by a task group. This group is composed by CNEN's officials and representatives of organizations, enterprises and public agencies involved in the related area. Once the first version of the proposed regulation is ready, it is formally open to consultation and posted at CNEN website for a period of time. The suggestions, therein presented on-line, are analyzed by the task group and the conclusions are also posted at the site; those considered pertinent are incorporated to proposed regulation. As an example, the public consultation results obtained in 2008 with the revision of the CNEN-NN-6.02: Licensing of Radioactive Facilities regulation, are presented. Such results cover two aspects: the analysis of the participants profile and the analysis of the contributions. Public participation in the elaboration of nuclear regulations is a new way for CNEN to know the licensees and public demands, doubts and needs. This tool has demonstrated usefulness and therefore must be maintained by the regulatory body. (author)

  20. Isolation of nuclear proteins from flax (Linum usitatissimum L. seed coats for gene expression regulation studies

    Directory of Open Access Journals (Sweden)

    Renouard Sullivan

    2012-01-01

    Full Text Available Abstract Background While seed biology is well characterized and numerous studies have focused on this subject over the past years, the regulation of seed coat development and metabolism is for the most part still non-elucidated. It is well known that the seed coat has an essential role in seed development and its features are associated with important agronomical traits. It also constitutes a rich source of valuable compounds such as pharmaceuticals. Most of the cell genetic material is contained in the nucleus; therefore nuclear proteins constitute a major actor for gene expression regulation. Isolation of nuclear proteins responsible for specific seed coat expression is an important prerequisite for understanding seed coat metabolism and development. The extraction of nuclear proteins may be problematic due to the presence of specific components that can interfere with the extraction process. The seed coat is a rich source of mucilage and phenolics, which are good examples of these hindering compounds. Findings In the present study, we propose an optimized nuclear protein extraction protocol able to provide nuclear proteins from flax seed coat without contaminants and sufficient yield and quality for their use in transcriptional gene expression regulation by gel shift experiments. Conclusions Routinely, around 250 μg of nuclear proteins per gram of fresh weight were extracted from immature flax seed coats. The isolation protocol described hereafter may serve as an effective tool for gene expression regulation and seed coat-focused proteomics studies.

  1. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    Science.gov (United States)

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Nuclear deformability and telomere dynamics are regulated by cell geometric constraints.

    Science.gov (United States)

    Makhija, Ekta; Jokhun, D S; Shivashankar, G V

    2016-01-05

    Forces generated by the cytoskeleton can be transmitted to the nucleus and chromatin via physical links on the nuclear envelope and the lamin meshwork. Although the role of these active forces in modulating prestressed nuclear morphology has been well studied, the effect on nuclear and chromatin dynamics remains to be explored. To understand the regulation of nuclear deformability by these active forces, we created different cytoskeletal states in mouse fibroblasts using micropatterned substrates. We observed that constrained and isotropic cells, which lack long actin stress fibers, have more deformable nuclei than elongated and polarized cells. This nuclear deformability altered in response to actin, myosin, formin perturbations, or a transcriptional down-regulation of lamin A/C levels in the constrained and isotropic geometry. Furthermore, to probe the effect of active cytoskeletal forces on chromatin dynamics, we tracked the spatiotemporal dynamics of heterochromatin foci and telomeres. We observed increased dynamics and decreased correlation of the heterochromatin foci and telomere trajectories in constrained and isotropic cell geometry. The observed enhanced dynamics upon treatment with actin depolymerizing reagents in elongated and polarized geometry were regained once the reagent was washed off, suggesting an inherent structural memory in chromatin organization. We conclude that active forces from the cytoskeleton and rigidity from lamin A/C nucleoskeleton can together regulate nuclear and chromatin dynamics. Because chromatin remodeling is a necessary step in transcription control and its memory, genome integrity, and cellular deformability during migration, our results highlight the importance of cell geometric constraints as critical regulators in cell behavior.

  3. Improving the regulation of safety at DOE nuclear facilities. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    The report strongly recommends that, with the end of the Cold War, safety and health at DOE facilities should be regulated by outside agencies rather than by DOE itself. The three major recommendations are: under any regulatory scheme, DOE must maintain a strong internal safety management system; essentially all aspects of safety at DOE`s nuclear facilities should be externally regulated; and existing agencies rather than a new one should be responsible for external regulation.

  4. Improving the regulation of safety at DOE nuclear facilities. Final report: Appendices

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    The report strongly recommends that, with the end of the Cold War, safety and health at DOE facilities should be regulated by outside agencies rather than by any regulatory scheme, DOE must maintain a strong internal safety management system; essentially all aspects of safety at DOE`s nuclear facilities should be externally regulated; and existing agencies rather than a new one should be responsible for external regulation.

  5. Food packaging regulation in the United States and the European Union.

    Science.gov (United States)

    Heckman, Jerome H

    2005-06-01

    The regulation of food packaging has, indeed, become a global subject as the world's commercial channels have broadened since World War II. The first comprehensive regulatory statute governing the area was the Food Additives Amendment of 1958 in the United States, a modification of the 1938 Federal Food, Drug, and Cosmetic Act. Germany, Italy, The Netherlands, and Belgium began regulatory activity in the early 1960s and the European Community set in motion its own work in this direction beginning in 1976. Companies in the United States and the Europe have been struggling with each of the laws since then. The regulatory systems employed on the two continents are superficially similar but this is far from the truth in actual practice. Each has its own special history and set of exemptions; they vary tremendously. Each has its cadre of supporters as well but a considerable lack of understanding afflicts regulators and the regulated on both sides of the Atlantic. This three part report first discusses the history of the United States system and its characteristics; Book II covers the history of European Union regulations and their salient features; and Book III highlights the commonalities and differences in the systems, discusses their scientific basing points, and makes some recommendations as to how they can be brought closer together in the interests of harmonization and the removal of unnecessary trade barriers.

  6. NEW PROPOSAL FOR EUROPEAN UNION REGULATIONS ON MEDICAL DEVICES AND IN VITRO DIAGNOSTIC MEDICAL DEVICES

    Directory of Open Access Journals (Sweden)

    Mariela Yaneva-Deliverska

    2012-12-01

    Full Text Available Appropriate legislation is fundamental to ensuring the highest level of health protection and effective innovation. Until the 1990s, each European Union country had its own approach to device evaluation but governments needed to put in place policies that will address all elements related to medical devices, ranging from access to high quality, affordable products, through to their safe and appropriate use and disposal. In order to ensure that patients, consumers and healthcare professionals can reap the benefits of safe, effective and innovative medical devices, the European Commission has proposed two new Regulations. The first proposal is for Regulation on medical devices and is to replace Directive 90/385/EEC regarding active implantable medical devices and Directive 93/42/EEC regarding medical devices, while the second proposal is for a Regulation on in vitro diagnostic medical devices and is to replace Directive 98/79/EC. The proposed Regulations foresee to amend and clarify the scope of the legislation, to take into account scientific and technological progress.

  7. An Overview of the Regulation of Low Dose Radiation in the Nuclear and Non-nuclear Industries

    Energy Technology Data Exchange (ETDEWEB)

    Menon, Shankar; Valencia, Luis; Teunckens, Lucien

    2003-02-27

    Now that increasing numbers of nuclear power stations are reaching the end of their commercially useful lives, the management of the large quantities of very low level radioactive material that arises during their decommissioning has become a major subject of discussion, with very significant economic implications. Much of this material can, in an environmentally advantageous manner, be recycled for reuse without radiological restrictions. Much larger quantities--2-3 orders of magnitude larger--of material, radiologically similar to the candidate material for recycling from the nuclear industry, arise in non-nuclear industries like coal, fertilizer, oil and gas, mining, etc. In such industries, naturally occurring radioactivity is artificially concentrated in products, by-products or waste to form TENORM (Technologically Enhanced Naturally Occurring Radioactive Material). It is only in the last decade that the international community has become aware of the prevalence of TENORM, specially the activity levels and quantities arising in so many non-nuclear industries. The first reaction of international organizations seems to have been to propose different standards for the nuclear and non-nuclear industries, with very stringent release criteria for radioactive material from the regulated nuclear industry and up to thirty to a hundred times more liberal criteria for the release/exemption of TENORM from the as yet unregulated non-nuclear industries. There are significant strategic issues that need to be discussed and resolved. Some examples of these are: - Disposal aspects of long-lived nuclides, - The use of radioactive residues in building materials, - Commercial aspects of differing and discriminating criteria in competing power industries in a world of deregulated electric power production. Of even greater importance is the need for the discussion of certain basic issues, such as - The quantitative risk levels of exposure to ionizing radiation, - The need for in

  8. Convergence of Croatian Financial and Budget Regulations to the Framework and Practices of the European Union

    Directory of Open Access Journals (Sweden)

    Ivana MALETIĆ

    2010-03-01

    Full Text Available As of 2004 intensive preparatory activities for the accession of the Republic of Croatia into the European Union have started. Significant changes have been taking place in legislation, institutional and administrative respect. The so called “silent reform“ is changing the appearance and the way of work of state administration. Institutions acquire the rules and way of work of the European Union through the usage of pre-accession programmes. General opinion moves in the direction of successfulness, competitiveness, attainment of results and added values. Financial regulations regarding stipulation of budget processes have been changing through the introduction of the following elements: strategic planning, multi-annual budget framework, fiscal discipline, internal audit as well as financial management and control system based on clearly set work processes and procedures. This document provides the description of the most significant changes regarding financial management and budget regulations in the Republic of Croatia which have taken place in the course of adapting (developing the system to the European practices and rules.

  9. Joint congress of the European Association of Nuclear Medicine and the World Federation of Nuclear Medicine and Biology. Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1998-08-01

    This volume contains the abstracts of the 588 oral communications, the 774 poster presentations and the 35 technological sessions. The topics were as follows: cardiovascular diseases, oncology, neurology/psychiatry, general nuclear medicine, endocrinology/thyroid, infection/inflammation, hematology, pediatrics, radionuclide therapy, dosimetry, radiobiology, physics and instrumentation, radiopharmacy and radiochemistry. (MG)

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

    Science.gov (United States)

    Hozumi, Shunya; Aoki, Shun; Kikuchi, Yutaka

    2017-11-01

    Asymmetric nuclear positioning is observed during animal development, but its regulation and significance in cell differentiation remain poorly understood. Using zebrafish blastulae, we provide evidence that nuclear movement towards the yolk syncytial layer, which comprises extraembryonic tissue, occurs in the first cells fated to differentiate into the endoderm. Nodal signaling is essential for nuclear movement, whereas nuclear envelope proteins are involved in movement through microtubule formation. Positioning of the microtubule-organizing center, which is proposed to be crucial 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 independently of the Smad pathway, and this nuclear movement is associated with Smad signal transduction toward the nucleus. Our study provides insight into the function of nuclear movement in Smad signaling toward the nucleus, and could be applied to the control of TGFβ signaling. © 2017. Published by The Company of Biologists Ltd.

  11. The new European regulation on personal data protection: significant aspects for data processing for scientific research purposes

    National Research Council Canada - National Science Library

    Francesca Preite; Silvia Salardi; Rosaria Gesuita; Simona Villani; Paolo Trerotoli; Vincenzo Guardabasso; Antonella Zambon

    2017-01-01

    On 27 April 2016, after a troubled gestation,, Regulation 2016/6791 of the European Parliament and of the Council on the protection of natural persons with regard to the processing of personal data...

  12. The role of research in nuclear regulation: Opening remarks

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, J.M.

    1997-01-01

    More than 20 years ago, the Energy Reorganization Act of 1974 created the USNRC and that same act provided for an office of nuclear regulatory research. It`s what is called a statutory office within the NRC. In providing for an NRC research program, our Congress had several things to say about the character of the research that would be performed. First, NRC should perform such research as is necessary for the effective performance of the Commission`s licensing and related regulatory functions. Second, the research may be characterized as confirmatory reassessment related to the safe operation and the protection of commercial reactors and other nuclear materials. Third, the NRC should have an independent capability for developing and analyzing technical information related to reactor safety, safeguards, and environmental protection in support of both the licensing and regulatory processes. Fourth, the research should not go beyond the need for confirmatory assessment, because the NRC should never be place in a position of having generated and then having to defend basic design data of its own. This has been and continues to be the role of research at the NRC. Somewhat different purposes might apply for regulatory agencies in other countries. Several regulatory agencies are represented here on this panel, so some of these difference may be discussed.

  13. Regulation of mRNA Trafficking by Nuclear Pore Complexes

    Directory of Open Access Journals (Sweden)

    Amandine Bonnet

    2014-09-01

    Full Text Available Over the last two decades, multiple studies have explored the mechanisms governing mRNA export out of the nucleus, a crucial step in eukaryotic gene expression. During transcription and processing, mRNAs are assembled into messenger ribonucleoparticles (mRNPs. mRNPs are then exported through nuclear pore complexes (NPCs, which are large multiprotein assemblies made of several copies of a limited number of nucleoporins. A considerable effort has been put into the dissection of mRNA export through NPCs at both cellular and molecular levels, revealing the conserved contributions of a subset of nucleoporins in this process, from yeast to vertebrates. Several reports have also demonstrated the ability of NPCs to sort out properly-processed mRNPs for entry into the nuclear export pathway. Importantly, changes in mRNA export have been associated with post-translational modifications of nucleoporins or changes in NPC composition, depending on cell cycle progression, development or exposure to stress. How NPC modifications also impact on cellular mRNA export in disease situations, notably upon viral infection, is discussed.

  14. Regulations governing veterinary medicinal products containing genetically modified organisms in the European community.

    Science.gov (United States)

    Moulin, G

    2005-04-01

    This paper describes particular aspects of the marketing of veterinary medicinal products (VMPs) that contain or consist of genetically modified micro-organisms (GMMs) or genetically modified organisms (GMOs). The regulatory requirements and the procedures applied in the European Union for each phase (pre-marketing, authorisation process, and post-authorisation labelling and monitoring) are explained. In most cases VMPs are subject to both pharmaceutical and GMO regulations. In the early stages of the process, before applications for marketing authorisation are submitted, the assessment of clinical trials and experiments in contained areas is principally the responsibility of national authorities. However, the marketing of all VMPs containing or consisting of GMOs must be authorised at European level, although the national authorities are informed and involved in the assessment process.

  15. The international regulation of climate engineering : Lessons from nuclear power

    NARCIS (Netherlands)

    Reynolds, J.L.(Jesse)

    Proposals for climate engineering—intentional large-scale interventions in climate systems—are increasingly under consideration as potential additional responses to climate change, yet they pose risks of their own. Existing international regulation of large-scale field testing and deployment is

  16. Nuclear calcium signalling in the regulation of brain function.

    Science.gov (United States)

    Bading, Hilmar

    2013-09-01

    Synaptic activity initiates biochemical processes that have various outcomes, including the formation of memories, increases in neuronal survival and the development of chronic pain and addiction. Virtually all activity-induced, long-lasting adaptations of brain functions require a dialogue between synapses and the nucleus that results in changes in gene expression. Calcium signals that are induced by synaptic activity and propagate into the nucleus are a major route for synapse-to-nucleus communication. Recent findings indicate that diverse forms of neuroadaptation require calcium transients in the nucleus to switch on the necessary genomic programme. Deficits in nuclear calcium signalling as a result of a reduction in synaptic activity or increased extrasynaptic NMDA receptor signalling may underlie the aetiologies of various diseases, including neurodegeneration and cognitive dysfunction.

  17. DMPD: Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17349209 Nuclear factor-kappaB: activation and regulation during toll-like receptor...vation and regulation during toll-like receptorsignaling. PubmedID 17349209 Title Nuclear factor-kappaB: act...ivation and regulation during toll-like receptorsignalin...signaling. Carmody RJ, Chen YH. Cell Mol Immunol. 2007 Feb;4(1):31-41. (.png) (.svg) (.html) (.csml) Show Nuclear factor-kappaB: acti

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

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M. [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Heery, David M., E-mail: david.heery@nottingham.ac.uk [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)

    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.

  19. The main directions of adaptation regulation of admission to market of road transport in Ukraine according to European Union standards

    Directory of Open Access Journals (Sweden)

    V. A. Balin

    2014-10-01

    The peculiarities of legal regulation of individual elements of the transport sector, in particular concerning common rules for access to the market of transport services. In this regard, special attention is paid to the analysis of the Law of Ukraine «On the State Program of Adaptation of Ukraine to the European Union», the Association Agreement between Ukraine and the European Union and the relevant regulations of the European Union. Reveals the order in which the following requirements for companies involved in the activities of road transport operator. Considerable attention is paid to the coverage of liberalization road transport.

  20. Improving the Indico Framework at the European Organization for Nuclear Research - Internship Report - LEIC 2006/2007 (FEUP)

    CERN Document Server

    Ferreira, Jose Pedro

    2007-01-01

    This document describes the work developed by José Pedro Macedo Alves Ferreira, Informatics Engineering and Computing (LEIC) undergraduate student at the Engineering Faculty of the University of Porto (FEUP), in the context of the project "Improving the Indico Framework". The project took place at the European Organization for Nuclear Research (CERN), in the framework of both the Technical Student Program of this organization, and the curricular internship of the aforementioned degree. The contents of this report refer to the internship period, the first half of the one-year Technical Student program. The project aimed to introduce usability improvements into an already existing web application, the Indico platform, a integrated system for event scheduling and management, which was initially developed as a European project and continued by CERN, being currently used by several institutions worldwide. Indico presented some usability issues that for long had been noticed by the users and required correction, m...

  1. Life cycle environmental impacts of vacuum cleaners and the effects of European regulation

    Energy Technology Data Exchange (ETDEWEB)

    Gallego-Schmid, Alejandro, E-mail: alejandro.gallegoschmid@manchester.ac.uk; Mendoza, Joan Manuel F.; Jeswani, Harish Kumar; Azapagic, Adisa

    2016-07-15

    Energy efficiency of vacuum cleaners has been declining over the past decades while at the same time their number in Europe has been increasing. The European Commission has recently adopted an eco-design regulation to improve the environmental performance of vacuum cleaners. In addition to the existing directive on waste electrical and electronic equipment (WEEE), the regulation could potentially have significant effects on the environmental performance of vacuum cleaners. However, the scale of the effects is currently unknown, beyond scant information on greenhouse gas emissions. Thus, this paper considers for the first time life cycle environmental impacts of vacuum cleaners and the effects of the implementation of these regulations at the European level. The effects of electricity decarbonisation, product lifetime and end-of-life disposal options are also considered. The results suggest that the implementation of the eco-design regulation alone will reduce significantly the impacts from vacuum cleaners (37%–44%) by 2020 compared with current situation. If business as usual continued and the regulation was not implemented, the impacts would be 82%–109% higher by 2020 compared to the impacts with the implementation of the regulation. Improvements associated with the implementation of the WEEE directive will be much smaller (< 1% in 2020). However, if the WEEE directive did not exist, then the impacts would be 2%–21% higher by 2020 relative to the impacts with the implementation of the directive. Further improvements in most impacts (6%–20%) could be achieved by decarbonising the electricity mix. Therefore, energy efficiency measures must be accompanied by appropriate actions to reduce the environmental impacts of electricity generation; otherwise, the benefits of improved energy efficiency could be limited. Moreover, because of expected lower life expectancy of vacuum cleaners and limited availability of some raw materials, the eco-design regulation should

  2. REGULATION OF PRODUCT CERTIFICATION AND STANDARDIZATION PROCESSES IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    Liudmyla Shabelnyk

    2016-11-01

    Full Text Available Research is aimed at investigation of current state of technical regulation system in European Union. Special attention is paid to peculiarities of standardization and certification in certain countries of EU in order to implement foreign experience in Ukraine. Despite the wide academic coverage of technical regulation issue, a range of issues remain unsolved, especially the problem of historical retrospective and possibility of positive experience implementation. Subject of study. Theoretical and methodological approaches to the regulation of certification and standardization of processes in the EU, as well as comparative analysis of the systems in the past and the present. Methodology. The survey is based on research of available publications on the topic, comparative analysis, induction and deduction. Issues of standardization and certification were widely discovered by numerous researchers: F.D. Duyvis (1960, W. Hesser and A. Inklaar (1998, C. Shapiro (1999, A. Richen and A. Steinhorst (2005. But in spite of the deep theoretical background of scientific works, it is obvious that the most important documents for technical regulations are ISO standards (especially ISO/ IEC 17021:2006 «Conformity assessment – Requirements for bodies providing audit and certification of management systems». Results. The article discovers relationship between main standardization bodies in EU, studies main legislative documents, reveals its historical retrospective and provides in-depth study of technical regulation system in Germany and the UK. Information from the article can be used for general understanding of main processes of technical regulation in EU; practical discovery of marking signs on the products and comparative analysis of standardization systems in different countries. Practical implications. It is important to mention practical demonstration of technical requirements in the EU: the signs marking Certificate IN, Certificate VS, Certificate

  3. CONSIDERATIONS REGARDING THE PATRIMONIAL INVENTORY IN THE SPIRIT OF EUROPEAN ACCONTING REGULATIONS

    OpenAIRE

    AVRAM Veronel; TOGOE Greti Daniela

    2012-01-01

    The accounting rules appeared in late 2009: the Order of the Minister of the Public Finances no. 3055 / October 29, 2009 for the approval of the Accounting Regulations in accordance with the European directives and the Minister of Public Finance Order no. 2861 / October 9, 2009 on the organization and the performance of the inventory of the assets items, liabilities and equity, have made many changes both in terms of how to conduct the inventory and how to find the differences between the exi...

  4. NATO Nuclear Reductions and the Assurance of Central and Eastern European Allies

    Science.gov (United States)

    2013-10-01

    Russian nonstrategic nuclear capabilities are the focus of attention, particularly for the Balts and Poles. The nonstrategic capabilities include...proximity cuts both ways. Just as the Poles and Balts find unnerving the nonstrategic nuclear weapons based near their borders with Russia, they and

  5. TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.

    Science.gov (United States)

    McCallum, Katie C; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A

    2016-05-01

    The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Copyright © 2016 by the Genetics Society of America.

  6. TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans

    Science.gov (United States)

    McCallum, Katie C.; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A.

    2016-01-01

    The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. PMID:26920757

  7. The role of research in nuclear regulation: Status and future activities in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Soda, K. [Japan Atomic Energy Research Institute, Chyiyodaku, Tokyo (Japan)

    1997-01-01

    The role of nuclear regulation is grouped into the three categories in the Basic Safety Principles for Nuclear Power Plants, the INSAG-3 document of IAEA published in 1988. First category is to specify and develop standards and regulations for safety, and to issue licenses to operating organization. Second category is to inspect, monitor and review the safety performances of nuclear power plants and operating organizations. In the second category, corrective action may be ordered if it is found necessary after inspection, monitoring and review. The third category is to advocate safety research and disseminate safety information. Nuclear safety research is closely related to nuclear regulation. The licensing procedures of nuclear facilities requires a two step approach in Japan, that is, those who wish to construct and operate a nuclear plant must apply for a government approval for construction and operation. Safety examination is then performed first by the government, and the second examination is carried out by the Nuclear Safety Commission. In this process, research information is supplied to the Advisory Committee on Technical Matters which is under the Ministry of Trade and Industry and to the Committee on Examination of Reactor Safety which is under the Science and Technology Agency. Research organizations are asked by those Committees to provide data needed for safety examination and to perform safety analyses for verification of analyses submitted to the Committees by the licensees. in addition in the licensing procedures, examination guides needed for the safety examination are based on experimental data and analyses performed by research organizations by the government request.

  8. The role of research in nuclear regulation: A French perspective

    Energy Technology Data Exchange (ETDEWEB)

    Livolant, M. [Institut de Prot. et de Surete Nuc., Fontenay Aux Roses (France)

    1997-01-01

    Roughly speaking, the French Nuclear Protection and Safety Institute`s role is similar in the French situation to the NRC administration role but with less authority role, which corresponds to another body in France. They define themselves as a technical support of the safety authorities. On the other hand, they have their own research laboratories. Among them, the most famous are the Phebus reactor and the Cabri reactor about which we have heard a lot these two days. They work on safety but also on protection of man and environment, management of accident conditions, security of transport, and safeguards. They have a relationship with utilities and with government authorities. With the utilities they have two types of technical evaluations. They make detailed technical studies of the safety reports presented to the authorities by the utility. On the research side, they participate in common research programs to resolve issues and to increase knowledge and understanding about safety related questions. With the governmental authorities, their role is to give advice on safety reports of existing or being-built installations and on more general policy questions like, for example, the safety principle to apply to the next generation of power plants. The decisions are left to the safety authorities, but they give a lot of advice and detailed studies about questions of safety.

  9. The role of research in nuclear regulation: An NRC perspective

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, D.L.

    1997-01-01

    The role of research in the US Nuclear Regulatory Commission was broadly defined by the US Congress in the Energy Reorganization Act of 1975. This Act empowered the Commission to do research that it deems necessary for the performance of its licensing and regulatory functions. Congress cited a need for an independent capability that would support the licensing and regulatory process through the development and analysis of technical information related to reactor safety, safeguards and environmental protection. Motivation for establishing such a safety research function within the regulatory agency is the need to address the defects, abnormal occurrences and shutdowns involving light water reactors. Congress further stated that the NRC should limit its research to {open_quotes}confirmatory assessment{close_quotes} and that the Agency {open_quotes}should never be placed in a position to generate, and then have to defend, basic design data of its own.{close_quotes} The author reviews the activities of the research arm as related to regulatory research, performed in the past, today, and projected for the future. NRC`s public health and safety mission demands that its research products be developed independently from its licensees; be credible and of the highest technical quality as established through peer review; and open to the public scrutiny through publication in technical journals as well as NRC documents. A special trust is placed on regulatory research through the products it produces as well as the three dimensions that underlie the processes through which they are produced.

  10. Building the European Research Area in nuclear fission pioneering steps in actinide science

    Energy Technology Data Exchange (ETDEWEB)

    Forsstroem, Hans

    2004-07-01

    The concept of the European Research Area (ERA) aims at closer development of research policies in Europe and closer networking of research capacities, to reduce fragmentation of research in Europe. The goal is to make European research more effective and competitive. Several approaches are made to create ERA. The European Research Framework Programme is one tool in this context, with the introduction of the new instruments, Integrated Projects, Networks of Excellence and Integrated Infrastructure Initiatives. Actinide science is one area that could benefit from better coordination and more effective use of the research capacities, both human and physical. The European Commission is thus funding a Network of Excellence (ACTINET-6) and an Integrated Project (EUROPART) in this area within the sixth EURATOM Framework Programme. (author)

  11. Evidence for ubiquitin-regulated nuclear and subnuclear trafficking among Paramyxovirinae matrix proteins.

    Directory of Open Access Journals (Sweden)

    Mickey Pentecost

    2015-03-01

    Full Text Available The paramyxovirus matrix (M protein is a molecular scaffold required for viral morphogenesis and budding at the plasma membrane. Transient nuclear residence of some M proteins hints at non-structural roles. However, little is known regarding the mechanisms that regulate the nuclear sojourn. Previously, we found that the nuclear-cytoplasmic trafficking of Nipah virus M (NiV-M is a prerequisite for budding, and is regulated by a bipartite nuclear localization signal (NLSbp, a leucine-rich nuclear export signal (NES, and monoubiquitination of the K258 residue within the NLSbp itself (NLSbp-lysine. To define whether the sequence determinants of nuclear trafficking identified in NiV-M are common among other Paramyxovirinae M proteins, we generated the homologous NES and NLSbp-lysine mutations in M proteins from the five major Paramyxovirinae genera. Using quantitative 3D confocal microscopy, we determined that the NES and NLSbp-lysine are required for the efficient nuclear export of the M proteins of Nipah virus, Hendra virus, Sendai virus, and Mumps virus. Pharmacological depletion of free ubiquitin or mutation of the conserved NLSbp-lysine to an arginine, which inhibits M ubiquitination, also results in nuclear and nucleolar retention of these M proteins. Recombinant Sendai virus (rSeV-eGFP bearing the NES or NLSbp-lysine M mutants rescued at similar efficiencies to wild type. However, foci of cells expressing the M mutants displayed marked fusogenicity in contrast to wild type, and infection did not spread. Recombinant Mumps virus (rMuV-eGFP bearing the homologous mutations showed similar defects in viral morphogenesis. Finally, shotgun proteomics experiments indicated that the interactomes of Paramyxovirinae M proteins are significantly enriched for components of the nuclear pore complex, nuclear transport receptors, and nucleolar proteins. We then synthesize our functional and proteomics data to propose a working model for the ubiquitin-regulated

  12. The role of nuclear particle physics in European science and education

    CERN Multimedia

    1970-01-01

    In conjunction with the formal papers presented at the session of the CERN Council reported earlier in this issue, a booklet entitled 'The European 300 GeV Accelerator Programme' (more colloquially known as 'the white book') has been prepared. It aims to present the 300 GeV project and its background in a more general way. We reproduce here the opening chapter which puts the research at CERN and related Laboratories in Europe in the context of European science and education.

  13. Ethical and legal framework and regulation for off-label use: European perspective

    Directory of Open Access Journals (Sweden)

    Lenk C

    2014-07-01

    Full Text Available Christian Lenk,1 Gunnar Duttge2 1Institute for History, Theory and Ethics of Medicine, Ulm University, Ulm, Germany; 2Center for Medical Law, Göttingen University, Göttingen, Germany Abstract: For more than 20 years the off-label use of drugs has been an essential part of the ethical and legal considerations regarding the international regulation of drug licensing. Despite a number of regulatory initiatives in the European Union, there seems to remain a largely unsatisfactory situation following a number of critical descriptions and statements from actors in the field. The present article gives an overview of the ethical and legal framework and developments in European countries and identifies existing problems and possible pathways for solutions in this important regulatory area. In addition to the presentation of the ethical and legal foundations, some attention is given to criticisms from medical practitioners to the current handling of off-label drug use. The review also focuses on the situation confronted by patients and physicians when off-label prescriptions are necessary. Through legal descriptions from a number of countries, possible solutions for future discussion of European health care policy are selected and explained. Keywords: ethics, law, Europe, health care policy 

  14. European regulations on nutraceuticals, dietary supplements and functional foods: a framework based on safety.

    Science.gov (United States)

    Coppens, Patrick; da Silva, Miguel Fernandes; Pettman, Simon

    2006-04-03

    This article describes the legislation that is relevant in the marketing of functional foods in the European Union (EU), how this legislation was developed as well as some practical consequences for manufacturers, marketers and consumers. It also addresses some concrete examples of how the EU's safety requirements for food products have impacted a range of product categories. In the late nineties, research into functional ingredients was showing promising prospects for the use of such ingredients in foodstuffs. Due mainly to safety concerns, these new scientific developments were accompanied by an urgent call for legislation. The European Commission 2000 White Paper on Food Safety announced some 80 proposals for new and improved legislation in this field. Among others, it foresaw the establishment of a General Food Law Regulation, laying down the principles of food law and the creation of an independent Food Authority endowed with the task of giving scientific advice on issues based upon scientific risk assessment with clearly separated responsibilities for risk assessment, risk management and risk communication. Since then, more than 90% of the White Paper proposals have been implemented. However, there is not, as such, a regulatory framework for 'functional foods' or 'nutraceuticals' in EU Food Law. The rules to be applied are numerous and depend on the nature of the foodstuff. The rules of the general food law Regulation are applicable to all foods. In addition, legislation on dietetic foods, on food supplements or on novel foods may also be applicable to functional foods depending on the nature of the product and on their use. Finally, the two proposals on nutrition and health claims and on the addition of vitamins and minerals and other substances to foods, which are currently in the legislative process, will also be an important factor in the future marketing of 'nutraceuticals' in Europe. The cornerstone of EU legislation on food products, including

  15. Regulations applicable to plant food supplements and related products in the European Union.

    Science.gov (United States)

    Silano, Vittorio; Coppens, Patrick; Larrañaga-Guetaria, Ainhoa; Minghetti, Paola; Roth-Ehrang, René

    2011-12-01

    This paper deals with the current regulatory and legal settings of traditional plant food supplements and herbal medicinal products in the European Union (EU). Marketing of botanicals in foods and food supplements in the EU is subject to several provisions of food law, which cover aspects of safety, production, labelling and product composition, including the use of additives and maximum levels of contaminants and residues. However, due to limited harmonization at the EU level, specific national regulations adopted at a Member State level also apply and mutual recognition is the mechanism through which such products can be marketed in EU countries other than those of origin. Unlike food supplements, marketing of traditional herbal medicinal products is regulated by an ad hoc Directive (i.e. Directive 2004/24/EC) covering in detail all the relevant aspects of these products, including a facilitated registration procedure at national level. However, by distinguishing traditional herbal medicinal products from plant food supplements and establishing selective marketing modalities for these two product categories, the EU has been confronted with implementation difficulties for traditional herbal medicinal products and a lack of homogeneity in the regulatory approaches adopted in different EU Member States. In fact, currently the nature of the commercial botanical products made available to consumers as traditional medicinal products or food supplements, depends largely on the EU Member State under consideration as a consequence of how competent National Authorities and manufacturing companies interpret and apply current regulations rather than on the intrinsic properties of the botanical products and their constituents. When the EU approach is compared with approaches adopted in some non-European countries to regulate these product categories, major differences become evident.

  16. Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

    Science.gov (United States)

    Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

    2017-08-15

    Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.

  17. Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID.

    Directory of Open Access Journals (Sweden)

    Quy Le

    2015-09-01

    Full Text Available AID (Activation Induced Deaminase deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram CpG methylation in early development. AID is potentially highly mutagenic, and it causes genomic instability evident as translocations in B cell malignancies. Here we show that AID is cell cycle regulated. By high content screening microscopy, we demonstrate that AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase, and that mutations that affect regulatory phosphorylation or catalytic activity can alter AID stability and abundance. We directly test the role of cell cycle regulation by fusing AID to tags that destabilize nuclear protein outside of G1 or S-G2/M phases. We show that enforced nuclear localization of AID in G1 phase accelerates somatic hypermutation and class switch recombination, and is well-tolerated; while nuclear AID compromises viability in S-G2/M phase cells. We identify AID derivatives that accelerate somatic hypermutation with minimal impact on viability, which will be useful tools for engineering genes and proteins by iterative mutagenesis and selection. Our results further suggest that use of cell cycle tags to regulate nuclear stability may be generally applicable to studying DNA repair and to engineering the genome.

  18. Opinion paper food supplements: the European regulation and its application in France. Thoughts on safety of food supplements.

    Science.gov (United States)

    Maixent, J M

    2012-06-30

    The first definition of food supplements in France was established by decree 96-307 of April 10th 1996. In 2002, the European Community adopted a regulation for food supplements (European Directive 2002/46/CE June 10th). This was an important event in the regulation of food supplements. The European regulation was adopted in France, with some modifications, by decree 2006-352 of March 20th 2006. The European Regulation on food supplements is more defined than those for any other food types and is exemplary. The Regulation on addition of vitamins and minerals to food differs from the regulation on the addition of other substances such as amino acids, essential fatty acids, fibers, carbohydrates, various plant, and herbal extracts. While the Regulation includes vitamins and minerals to the positive list of supplements, other substances are included in the negative list of supplements. According to the Regulation, substances added to food supplements must have a nutritional or physiological effect. The increased use of food supplements led to the creation of a department specialized in the safety of food supplement. The safety of food supplements is a permanent concern for sanitary authorities. These authorities have recently combined scientific methodological approaches and a collective expertise to implement and monitor simple and useful rules that insure consumer's safety. Safety laws aim to protect the consumers of food supplements.

  19. Highlights of the Annual Congress of the European Association of Nuclear Medicine, Istanbul, 2005: the incremental value of nuclear medicine for patient management and care

    Energy Technology Data Exchange (ETDEWEB)

    Cuocolo, Alberto; Acampa, Wanda; Varrone, Andrea; Salvatore, Marco [University of Naples Federico II, Department of Biomorphological and Functional Sciences, Napoli (Italy); Institute of Biostructures and Bioimages of the National Council of Research, Naples (Italy)

    2006-03-15

    The 2005 Annual Congress of the European Association of Nuclear Medicine (EANM) took place in Istanbul on October 15-19, under the chairmanship of Professor Hatice Durak. The programme was of excellent quality and represented a further step towards the achievement of a standardized EANM congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success: there were more than 4,000 participants, and 1,670 abstracts were received. Of these, 1,399 were accepted for oral or poster presentations, with a rejection rate of 16.2%. The original investigations presented were related to different areas of nuclear medicine, and addressed particularly 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, nephrology, and infection and inflammation. It is noteworthy that a number of studies presented at this congress focussed on the quantitative interpretation of the imaging data and on pragmatic endpoints, such as adverse outcomes, and identified when nuclear medicine procedures achieved clinical effectiveness for patient care and management. These and many other studies presented at the congress demonstrate once more the crucial role that nuclear medicine has to play in contemporary medicine. 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 proceedings book, published as volume 32, supplement 1 of the Eur J Nucl Med Mol Imaging in September 2005. (orig.)

  20. Applying and adapting the Swedish regulatory system for decommissioning to nuclear power reactors - The regulator's perspective.

    Science.gov (United States)

    Amft, Martin; Leisvik, Mathias; Carroll, Simon

    2017-03-16

    Half of the original 13 Swedish nuclear power reactors will be shut down by 2020. The decommissioning of these reactors is a challenge for all parties involved, including the licensees, the waste management system, the financing system, and the Swedish Radiation Safety Authority (SSM). This paper presents an overview of the Swedish regulations for decommissioning of nuclear facilities. It describes some of the experiences that SSM has gained from the application of these regulations. The focus of the present paper is on administrative aspects of decommissioning, such as SSM's guidelines, the definition of fundamental concepts in the regulatory framework, and a proposed revision of the licensing process according to the Environmental Act. These improvements will help to streamline the administration of the commercial nuclear power plant decommissioning projects that are anticipated to commence in Sweden in the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The nuclear industry and its European markets; L`industrie nucleaire et ses marches en Europe

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-31

    This study gives an overview of the worldwide nuclear energy demand and reviews the different markets which are classified as `mature` (uranium extraction, enrichment, conversion and reactors building), `developing` (reprocessing, MOX fuel fabrication, maintenance and services) and `emerging` (waste treatment and dismantling). Then, the study analyzes the evolution of demand and the answers of companies and presents the strategies and performances of nuclear industry leaders. (J.S.)

  2. Transposition of the new European Union audit regulation into the Croatian national law

    Directory of Open Access Journals (Sweden)

    Sanja Sever Mališ

    2016-11-01

    Full Text Available The audit reform in the EU had as a consequence the adoption of the new regulatory framework. The European Parliament adopted Directive 2014/56/EU amending the Directive 2006/43/EC on statutory audit in the EU and the EU Regulation No. 537/2014 containing requirements that relate specifically to the statutory audit of public interest entities. Each Member State needs to transpose the Directive into its national legislation and also ensure its implementation. Within the framework of transposing the Directive into the national regulation, each Member State had many options that allows them to tailor the provisions of the national law according to their needs and specific aspects of the national audit markets. However, the number of options brings risks that are connected to additional audit procedures and inefficiencies in the process of performing audit with the potential effects on the quality and cost of audits. The aim of this article is to analyse the most important (not used options of the Directive and Regulation according to the Croatian national legislation. In that sense, the article provides information about the definition of statutory audit and the subjects of statutory audit as well as the definition of public interest entities in Croatia. In addition, the audit profession in Croatia is analysed in the context of the “European audit passport”. The results of this research can be a base for future comparisons between Croatia and the other EU Member States. Finally, the implementation of this provisions will answer the question: Does the implementation of different options bring convergence or divergence within the single EU audit services market?

  3. The Swedish Radiation Protection Institute's regulations concerning the final management of spent nuclear fuel and nuclear waste - with background and comments

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-11-01

    This report presents and comments on the Swedish Radiation Protection Institute's Regulations concerning the Protection of Human Health and the Environment in connection with the Final Management of Spent Nuclear Fuel or Nuclear Waste, SSI FS 1998: 1.

  4. Highlights of the Annual Congress of the European Association of Nuclear Medicine, Helsinki 2004, and a dash of horizon scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ell, Peter J. [Middlesex Hospital, Institute of Nuclear Medicine, London (United Kingdom)

    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 Imagingin August 2004. (orig.)

  5. WTEC panel report on European nuclear instrumentation and controls. Final report

    Energy Technology Data Exchange (ETDEWEB)

    White, J.D.; Lanning, D.D.; Johnson, P.M.H. [eds.] [World Technology Evaluation Center, Baltimore, MD (United States); Shelton, R.D. [World Technology Evaluation Center, Baltimore, MD (United States)

    1991-12-01

    A study of instrumentation and controls (I and C) technology used in nuclear power plants in Europe was conducted by a panel of US specialists. This study plants in Europe was conducted by a panel of US specialists. This study included a review of the literature on the subject, followed by a visit to some of the leading organizations in Europe in the field nuclear I and C. Areas covered are: (1) role of the operator and control room design; (2) transition from analog to digital technology; (3) computerized operator support systems for fault management; (4) control strategies and techniques; (5) Nuclear power plant I and C architecture; (6) instrumentation and (7) computer standards and tools. The finding relate to poor reactions.

  6. Comparative analysis of public service advertising regulation in Russian Federation and European countries

    Directory of Open Access Journals (Sweden)

    Nureeva Maria, R.

    2015-03-01

    Full Text Available In modern world public service advertising is a direct reflection of social values, humanistic relationships between people, level of cultural development of the society. The aim of PSA is to form social challenges in the society’s mind, to lead to reforms in social sphere. Underestimation and inattentiveness towards social problems could lead to loss of moral values, destruction of culture and forming the basis for aggravation in relation between different levels of society. The tasks of the research are the following: to analyze the legislative base of public service advertising, to determine their strengths and weaknesses; to find out typical problems arising while PSA realization in Russia and Europe; to determine the main obstacles, preventing from creation of efficient and qualitative PSA and to find out and provide the measures of creating an efficient and qualitative public service advertising. In the first part of the paper we compare PSA regulation, sort out PSA legislative and practical issues in Russia and Europe. In the second part we consider the process of efficient PSA realization. For this purpose there were investigated the main obstacles on the way of realization of PSA strategy in Russia and Europe, possibilities of application of marketing mix approach. Though the level of social activity has increased in Russia especially in recent years, PSA market is only in the process of formation – there are huge potentials for investigations, initiatives and improvements. We could conclude that modern PSA legal base of Russian Federation restrains the development of PSA in our country and puts obstacles in the way of PSA participants: government, non-commercial organizations and businesses. In comparison with EU our country fails behind European countries both in the level of legislative regulation and practical experience. The most important difference between PSA practice in Russia and in Europe is that in Europe there is clear

  7. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito [Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Lee, Hong-Jen; Lee, Heng-Huan [Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States); Hung, Mien-Chie, E-mail: mhung@mdanderson.org [Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States); Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung 404, Taiwan (China); Asia University, Taichung 413, Taiwan (China)

    2010-09-03

    Research highlights: {yields} ARF1 activation is involved in the EGFR transport to the ER and the nucleus. {yields} Assembly of {gamma}-COP coatomer mediates EGFR transport to the ER and the nucleus. {yields} Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH{sub 2}-terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with {gamma}-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

  8. A study on environmental regulation and public inquiry system of nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hun [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Kang, Chang Sun; Son, Ki Yon; Cho, Young Ho; Yang, Ji Won; Lee, Young Wook; Ko, Hyun Suk [Seoul National Univ., Seoul (Korea, Republic of)

    2000-03-15

    Public hearing system for domestic and foreign nuclear facilities are investigated and analyzed. As a result, Korean public hearing system are developed. Atomic Energy Act, Environmental Impact Assessment Act and Administrative Procedure Act of Korea are reviewed and appropriate acts, regulations, procedures and mandates of foreign countries including U.S.A are reviewed and analyzed. On the basis of these results the role of device to collect public opinion is identified for nuclear facility of Korea and the elementary principle of the system and recommendations are developed.

  9. The nuclear IκB family of proteins controls gene regulation and immune homeostasis.

    Science.gov (United States)

    MaruYama, Takashi

    2015-10-01

    The inhibitory IκB family of proteins is subdivided into two groups based on protein localization in the cytoplasm or in the nucleus. These proteins interact with NF-κB, a major transcription factor regulating the expression of many inflammatory cytokines, by modulating its transcriptional activity. However, nuclear IκB family proteins not only interact with NF-κB to change its transcriptional activity, but they also bind to chromatin and control gene expression. This review provides an overview of nuclear IκB family proteins and their role in immune homeostasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

    Science.gov (United States)

    Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

    2017-10-19

    Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Tracking of Airborne Radionuclides from the Damaged Fukushima Dai-Ichi Nuclear Reactors by European Networks

    DEFF Research Database (Denmark)

    Masson, O.; Baeza, A.; Bieringer, J.

    2011-01-01

    Radioactive emissions into the atmosphere from the damaged reactors of the Fukushima Dai-ichi nuclear power plant (NPP) started on March 12th, 2011. Among the various radionuclides released, iodine-131 (131I) and cesium isotopes (137Cs and 134Cs) were transported across the Pacific toward the North...

  12. The protection of the European trademark in the light of the EU Regulation 2015/2424 of the European Parliament and of the Council

    Directory of Open Access Journals (Sweden)

    I.C. MURZEA

    2017-07-01

    Full Text Available The present paper aims to analyze the novelty aspects brought about by the EU Regulation 2015/2424 of the European Parliament and of the Council which came into force March 23rd, 2016, regarding the trademark, especially aspects regarding its protection and the rights it provides, as opposed to national law and the old community law. We will consider both theoretical aspects, as well as jurisprudence issues in this domain.

  13. Towards reasonable European shale gas regulation - The European commission's 2014 recommendation and communication on shale gas extraction

    NARCIS (Netherlands)

    Fleming, Ruven

    2015-01-01

    Following years of deliberation, the European Union released a Recommendation on unconventional hydrocarbons and a related Communication in 2014. Although these documents are not legally binding on member states, they are nevertheless of great significance as they indicate, for the first time, the

  14. Radioactivity monitoring and import regulation of the contaminated foodstuffs in Japan following the Chernobyl nuclear power plant accident

    Energy Technology Data Exchange (ETDEWEB)

    Izumo, Yoshiro [Institute of Public Health, Tokyo (Japan)

    1997-03-01

    Radioactivity monitoring and import regulation of the contaminated foodstuffs executed by Minstry of Health and Welfare following the Chernobyl nuclear plant accident were reviewed as follows; (1) background of socio-psychological effects and environmental radioactivity leading to the regulation (to may 3, 1986); (2) intial intervention for imported foodstuffs in Japan (may 8, `86), and (3) in european countries (to may 31, `86), immediately after the Accident, respectively; (4) determination of the interim driven intervention level for radionuclides in imported foodstuffs (({sup 134}Cs + {sup 137}Cs): 370 Bq/Kg) and activation of the monitoring, (5) outline of the monitoring with elapsed time, number of foodstuffs monitored, number of foodstuffs exceeded radioactivity of the intervention level and re-exported; (6) guideline in international trade of radioactive contaminated foodstuffs adopted by CODEX Alimentarius Commission (FAO/WHO) and the intervention level recommended by ICRP following the Accident; (7) discussion for problems and scopes in future based on the results of monitoring. As the results, a number of imported foodstuffs (about 75,000 samples at present) has been monitored, 55 samples exceeding the interim intervention level were re-exported to each export`s country, and socio-psychological doubts for radioactive contamination of imported foodstuffs have been dispersed. In addition, problems for several factors based on calculation of the interim intervention level, radioactivity level of foodstuffs exceeding about 50 Bq/Kg as radiocesiums and necessity of monitoring for the other radionuclides in foods except radiocesiums were also discussed. (author)

  15. Identification of a classic nuclear localization signal at the N terminus that regulates the subcellular localization of Rbfox2 isoforms during differentiation of NMuMG and P19 cells.

    Science.gov (United States)

    Wenzel, Manuel; Schüle, Martin; Casanovas, Sonia; Strand, Dennis; Strand, Susanne; Winter, Jennifer

    2016-12-01

    Nuclear localization of the alternative splicing factor Rbfox2 is achieved by a C-terminal nuclear localization signal (NLS) which can be excluded from some Rbfox2 isoforms by alternative splicing. While this predicts nuclear and cytoplasmic localization, Rbfox2 is exclusively nuclear in some cell types. Here, we identify a second NLS in the N terminus of Rbfox2 isoform 1A that is not included in Rbfox2 isoform 1F. Rbfox2 1A isoforms lacking the C-terminal NLS are nuclear, whereas equivalent 1F isoforms are cytoplasmic. A shift in Rbfox2 expression toward cytoplasmic 1F isoforms occurs during epithelial to mesenchymal transition (EMT) and could be important in regulating the activity and function of Rbfox2. © 2016 Federation of European Biochemical Societies.

  16. Identification of a chemical inhibitor for nuclear speckle formation: Implications for the function of nuclear speckles in regulation of alternative pre-mRNA splicing

    Energy Technology Data Exchange (ETDEWEB)

    Kurogi, Yutaro; Matsuo, Yota; Mihara, Yuki; Yagi, Hiroaki; Shigaki-Miyamoto, Kaya; Toyota, Syukichi; Azuma, Yuko [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Chuo-ku, Kumamoto 860-8555 (Japan); Igarashi, Masayuki [Laboratory of Disease Biology, Institute of Microbial Chemistry, Shinagawa-ku, Tokyo 141-0021 (Japan); Tani, Tokio, E-mail: ttani@sci.kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Chuo-ku, Kumamoto 860-8555 (Japan)

    2014-03-28

    Highlights: • We identified tubercidin as a compound inducing aberrant formation of the speckles. • Tubercidin causes delocalization of poly (A){sup +}RNAs from nuclear speckles. • Tubercidin induces dispersion of splicing factors from nuclear speckles. • Tubercidin affects alternative pre-mRNA splicing. • Nuclear speckles play a role in regulation of alternative pre-mRNA splicing. - Abstract: Nuclear speckles are subnuclear structures enriched with RNA processing factors and poly (A){sup +} RNAs comprising mRNAs and poly (A){sup +} non-coding RNAs (ncRNAs). Nuclear speckles are thought to be involved in post-transcriptional regulation of gene expression, such as pre-mRNA splicing. By screening 3585 culture extracts of actinomycetes with in situ hybridization using an oligo dT probe, we identified tubercidin, an analogue of adenosine, as an inhibitor of speckle formation, which induces the delocalization of poly (A){sup +} RNA and dispersion of splicing factor SRSF1/SF2 from nuclear speckles in HeLa cells. Treatment with tubercidin also decreased steady-state MALAT1 long ncRNA, thought to be involved in the retention of SRSF1/SF2 in nuclear speckles. In addition, we found that tubercidin treatment promoted exon skipping in the alternative splicing of Clk1 pre-mRNA. These results suggest that nuclear speckles play a role in modulating the concentration of splicing factors in the nucleoplasm to regulate alternative pre-mRNA splicing.

  17. AKT and 14-3-3 Regulate Notch4 Nuclear Localization

    Science.gov (United States)

    Ramakrishnan, Gopalakrishnan; Davaakhuu, Gantulga; Chung, Wen Cheng; Zhu, He; Rana, Ajay; Filipovic, Aleksandra; Green, Andrew R.; Atfi, Azeddine; Pannuti, Antonio; Miele, Lucio; Tzivion, Guri

    2015-01-01

    Members of the Notch family of transmembrane receptors, Notch1-4 in mammals, are involved in the regulation of cell fate decisions and cell proliferation in various organisms. The Notch4 isoform, which is specific to mammals, was originally identified as a viral oncogene in mice, Int3, able to initiate mammary tumors. In humans, Notch4 expression appears to be associated with breast cancer stem cells and endocrine resistance. Following ligand binding, the Notch4 receptor undergoes cleavage at the membrane and the Notch4-intracellular domain (ICD), translocates to the nucleus and regulates gene transcription. Little is known on the mechanisms regulating Notch4-ICD and its nuclear localization. Here, we describe the identification of four distinct AKT phosphorylation sites in human Notch4-ICD and demonstrate that AKT binds Notch4-ICD and phosphorylates all four sites in vitro and in vivo. The phosphorylation in cells is regulated by growth factors and is sensitive to phosphatidyl inositol-3 kinase (PI3K) inhibitors. This phosphorylation generates binding sites to the 14-3-3 regulatory proteins, which are involved in the regulation of nucleocytoplasmic shuttling of target proteins, restricting phosphorylated Notch4-ICD to the cytoplasm. Our findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. PMID:25740432

  18. Dual Targeting and Retrograde Translocation: Regulators of Plant Nuclear Gene Expression Can Be Sequestered by Plastids

    Directory of Open Access Journals (Sweden)

    Karin Krupinska

    2012-09-01

    Full Text Available Changes in the developmental or metabolic state of plastids can trigger profound changes in the transcript profiles of nuclear genes. Many nuclear transcription factors were shown to be controlled by signals generated in the organelles. In addition to the many different compounds for which an involvement in retrograde signaling is discussed, accumulating evidence suggests a role for proteins in plastid-to-nucleus communication. These proteins might be sequestered in the plastids before they act as transcriptional regulators in the nucleus. Indeed, several proteins exhibiting a dual localization in the plastids and the nucleus are promising candidates for such a direct signal transduction involving regulatory protein storage in the plastids. Among such proteins, the nuclear transcription factor WHIRLY1 stands out as being the only protein for which an export from plastids and translocation to the nucleus has been experimentally demonstrated. Other proteins, however, strongly support the notion that this pathway might be more common than currently believed.

  19. Implementation of manufacturing data management application in the scientific research project. Case: CERN, the European Organization for Nuclear Research

    CERN Document Server

    Saifoulina, Margarita

    2010-01-01

    This Bachelor’s thesis examined the implementation process of an MTF (Manufacturing and Test Folder) application in the CLIC (Compact Linear Collider) Radio Frequency Structure Development project for manufacturing data management purposes. The primary goal of the study was to investigate how MTF implementation and its integration with CERN EDMS (Engineering and Equipment Data Management System) system could facilitate product life cycle through the supply chain, and could affect on manufacturing operations performance in internaland external levels. The aim of the study was also to find out implementation differences within CERN (European Organization for Nuclear Research) projects. The study is divided into two parts: a qualitative theory section and an empirical section. In the theory section differences of features between PDM (Product Data Management), EDM (Engineering Data Management) and PLM (Product Life Cycle Management) systems were studied. The thesis examined the benefits and managerial challeng...

  20. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis

    Science.gov (United States)

    Bhat, Ramray; Belardi, Brian; Mori, Hidetoshi; Kuo, Peiwen; Tam, Andrew; Hines, William C.; Le, Quynh-Thu; Bertozzi, Carolyn R.; Bissell, Mina J.

    2016-01-01

    Branching morphogenesis in the mammary gland is achieved by the migration of epithelial cells through a microenvironment consisting of stromal cells and extracellular matrix (ECM). Here we show that galectin-1 (Gal-1), an endogenous lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes, induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D organotypic cultures. Surprisingly, Gal-1’s effects on mammary patterning were independent of its glycan-binding ability and instead required localization within the nuclei of mammary epithelia. Nuclear translocation of Gal-1, in turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end buds. Specifically, α2,6–sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Conversely, unsialylated LacNAc glycans, enriched in the epithelial ducts, sequestered Gal-1 in the extracellular environment, ultimately attenuating invasive potential. We also found that malignant breast cells possess higher levels of nuclear Gal-1 and α2,6–SA and lower levels of LacNAc than nonmalignant cells in culture and in vivo and that nuclear localization of Gal-1 promotes a transformed phenotype. Our findings suggest that differential glycosylation at the level of tissue microanatomy regulates the nuclear function of Gal-1 in the context of mammary gland morphogenesis and in cancer progression. PMID:27496330

  1. Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity.

    Directory of Open Access Journals (Sweden)

    Nadja Knoll

    Full Text Available There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1 16 nuclear regulators of mitochondrial genes, (2 91 genes for oxidative phosphorylation and (3 966 nuclear-encoded mitochondrial genes. Gene set enrichment analysis (GSEA showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents and a population-based GWAS sample (KORA F4, n = 1,743. A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th and 95(th percentile of the set of all gene-wise corrected p-values as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50 = 0.0103. This finding was not confirmed in the trios (p(GSEA,50 = 0.5991, but in KORA (p(GSEA,50 = 0.0398. The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50 = 0.1052, p(MAGENTA,75 = 0.0251. The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes.

  2. EuGH: Innocuousness of the nuclear fuel tax according to the European community law; EuGH: Europarechtliche Unbedenklichkeit der Kernbrennstoffsteuer

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2015-08-14

    The tax levied on nuclear fuel in Germany does not contravene European law. This was the conclusion of the European Court of Justice (ECJ) on 4 June. The ECJ has now, for the first time, made a clear decision on the admissibility of preliminary ruling proceedings referred to the ECJ and to the domestic constitutional court in parallel: Article 267 TFEU not only entitles the domestic court but even obliges it to submit issues that are decisive for the dispute to the European Court of Justice for interpretation or a decision on the applicability of European law. Such an obligation and the issue of incompatibility with European law did not depend on whether the same provision had been submitted to the domestic court for review or not. After all, even if a provision has been declared unconstitutional under domestic law it will still remain applicable for a certain period of time.

  3. European attitudes on the regulation of modern biotechnology and their consequences.

    Science.gov (United States)

    Cantley, Mark

    2012-01-01

    Modern biotechnology has gradually attracted ever greater interest over the past four decades, from ever-widening communities across the world--from academic scientists, of course, and then from industrialists, journalists, medical specialists, agricultural practitioners, environmental "experts," economists, trading companies--and, so far as it concerns regulation, above all from political interests whose product is indeed legislation. As the interests widened, conflicts developed: between departments, between sectors, between countries and between international agencies. The European Community made choices, bitterly contested; the battles on conducting and regulating the field release of GMOs (genetically modified organisms) were usually won--at least in Europe--by the environment ministries, often in conflict with agriculture and/or the research and science ministries. The result has been the construction over the past 30 y of an ever heavier regulatory burden on those who seek to develop and launch products based on the use of modern biotechnology. The pretense is labeled "the precautionary principle." No lives have been saved, but many jobs have been created in bureaucracies large and small around the world. So far as academia was concerned, their experiments and field trials were repeatedly wrecked by NGOs (non-governmental organizations) claiming thus to have saved mankind and the environment. This is a story of grave political failure in Europe with globally adverse consequences.

  4. Acetylation of the SUN protein Mps3 by Eco1 regulates its function in nuclear organization

    Science.gov (United States)

    Ghosh, Suman; Gardner, Jennifer M.; Smoyer, Christine J.; Friederichs, Jennifer M.; Unruh, Jay R.; Slaughter, Brian D.; Alexander, Richard; Chisholm, Robert D.; Lee, Kenneth K.; Workman, Jerry L.; Jaspersen, Sue L.

    2012-01-01

    The Saccharomyces cerevisiae SUN-domain protein Mps3 is required for duplication of the yeast centrosome-equivalent organelle, the spindle pole body (SPB), and it is involved in multiple aspects of nuclear organization, including telomere tethering and gene silencing at the nuclear membrane, establishment of sister chromatid cohesion, and repair of certain types of persistent DNA double-stranded breaks. How these diverse SUN protein functions are regulated is unknown. Here we show that the Mps3 N-terminus is a substrate for the acetyltransferase Eco1/Ctf7 in vitro and in vivo and map the sites of acetylation to three lysine residues adjacent to the Mps3 transmembrane domain. Mutation of these residues shows that acetylation is not essential for growth, SPB duplication, or distribution in the nuclear membrane. However, analysis of nonacetylatable mps3 mutants shows that this modification is required for accurate sister chromatid cohesion and for chromosome recruitment to the nuclear membrane. Acetylation of Mps3 by Eco1 is one of the few regulatory mechanisms known to control nuclear organization. PMID:22593213

  5. Controlling the atom. The beginnings of nuclear regulation 1946--1962

    Energy Technology Data Exchange (ETDEWEB)

    Mazuzan, G.T.; Walker, J.S.

    1997-08-01

    This book traces the early history of nuclear power regulation in the US. It focuses on the Atomic Energy Commission (AEC), the federal agency that until 1975 was primarily responsible for planning and carrying out programs to protect public health and safety from the hazards of the civilian use of nuclear energy. It also describes the role of other groups that figured significantly in the development of regulatory policies, including the congressional Joint Committee on Atomic Energy, federal agencies other than the AEC, state governments, the nuclear industry, and scientific organizations. And it considers changes in public perceptions of and attitudes toward atomic energy and the dangers of radiation exposure. The context in which regulatory programs evolved is a rich and complex mixture of political, legislative, legal, technological, scientific, and administrative history. The basic purpose of this book is to provide the Nuclear Regulatory Commission (NRC), which inherited responsibility for nuclear safety after Congress disbanded the AEC, and the general public with information on the historical antecedents and background of regulatory issues.

  6. The Drosophila NR4A nuclear receptor DHR38 regulates carbohydrate metabolism and glycogen storage.

    Science.gov (United States)

    Ruaud, Anne-Françoise; Lam, Geanette; Thummel, Carl S

    2011-01-01

    Animals balance nutrient storage and mobilization to maintain metabolic homeostasis, a process that is disrupted in metabolic diseases like obesity and diabetes. Here, we show that DHR38, the single fly ortholog of the mammalian nuclear receptor 4A family of nuclear receptors, regulates glycogen storage during the larval stages of Drosophila melanogaster. DHR38 is expressed and active in the gut and body wall of larvae, and its expression levels change in response to nutritional status. DHR38 null mutants have normal levels of glucose, trehalose (the major circulating form of sugar), and triacylglycerol but display reduced levels of glycogen in the body wall muscles, which constitute the primary storage site for carbohydrates. Microarray analysis reveals that many metabolic genes are mis-regulated in DHR38 mutants. These include phosphoglucomutase, which is required for glycogen synthesis, and the two genes that encode the digestive enzyme amylase, accounting for the reduced amylase enzyme activity seen in DHR38 mutant larvae. These studies demonstrate that a critical role of nuclear receptor 4A receptors in carbohydrate metabolism has been conserved through evolution and that nutritional regulation of DHR38 expression maintains the proper uptake and storage of glycogen during the growing larval stage of development.

  7. MASS MEDIA COMMUNICATION OF EMERGENCY ISSUES AND COUNTERMEASURES IN A NUCLEAR ACCIDENT: FUKUSHIMA REPORTING IN EUROPEAN NEWSPAPERS.

    Science.gov (United States)

    Gallego, Eduardo; Cantone, Marie Claire; Oughton, Deborah H; Perko, Tanja; Prezelj, Iztok; Tomkiv, Yevgeniya

    2017-04-01

    This paper presents the results of a large study of 1340 articles published by two major newspapers in six European countries (Belgium, Italy, Norway, Slovenia, Spain and Russia) in the first 2 months after the Fukushima Daiichi nuclear disaster. The focus of the analysis is on the application and overall impact of protective actions, both during the emergency phase and later, how the newspapers describe those actions, which differences were apparent between countries and what recommendations can be extracted in order to improve general communication about these issues. A clear lesson is that, even under uncertainty and recognising limitations, responsible authorities need to provide transparent, clear and understandable information to the public and the mass media right from the beginning of the early phase of any nuclear emergency. Clear, concise messages should be given. Mass media could play a key role in reassuring the public if the countermeasures are clearly explained. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Development and characterization of 79 nuclear markers amplifying in viviparous and oviparous clades of the European common lizard.

    Science.gov (United States)

    Horreo, J L; Peláez, M L; Suárez, T; Fitze, P S

    2018-02-01

    The European common lizard (Zootoca vivipara) is a widely distributed species across Europe and Asia exhibiting two reproductive modes (oviparity/viviparity), six major lineages and several sublineages. It has been used to tackle a large variety of research questions, nevertheless, few nuclear DNA sequence markers have been developed for this species. Here we developed 79 new nuclear DNA sequence markers using a clonation protocol. These markers were amplified in several oviparous and viviparous specimens including samples of all extant clades, to test the amplification success and their diversity. 49.4% of the markers were polymorphic and of those, 51.3% amplified in all and 94.9% amplified in 5-7 of the extant Z. vivipara clades. These new markers will be very useful for the study of the population structure, population dynamics, and micro/macro evolution of Z. vivipara. Cross-species amplification in four lizard species (Psammodromus edwardsianus, Podarcis muralis, Lacerta bilineata, and Takydromus sexlineatus) was positive in several of the markers, and six makers amplified in all five species. The large genetic distance between P. edwardsianus and Z. vivipara further suggests that these markers may as well be employed in many other species.

  9. The new European regulation on personal data protection: significant aspects for data processing for scientific research purposes

    Directory of Open Access Journals (Sweden)

    Francesca Preite

    2017-06-01

    Full Text Available On 27 April 2016, after a troubled gestation,, Regulation 2016/6791 of the European Parliament and of the Council on the protection of natural persons with regard to the processing of personal data and on the free movement of such data was finally published. The Regulation is to have a two-year transitional period, meaning it will actually enter into force in the first half of 2018.

  10. The changes in hazard classification and product notification procedures of the new European CLP and Cosmetics Regulations.

    Science.gov (United States)

    de Groot, Ronald; Brekelmans, Pieter; Herremans, Joke; Meulenbelt, Jan

    2010-01-01

    The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN-GHS) is developed to harmonize the criteria for hazard communication worldwide. The European Regulation on classification, labeling, and packaging of substances and mixtures [CLP Regulation (European Commission, EC) No 1272/2008] will align the existing European Union (EU) legislation to the UN-GHS. This CLP Regulation entered into force on January 20, 2009, and will, after a transitional period, replace the current rules on classification, labeling, and packaging for supply and use in Europe. Both old and new classifications will exist simultaneously until 2010 for substances and until 2015 for mixtures. The new hazard classification will introduce new health hazard classes and categories, with associated new hazard pictograms, signal words, Hazard (H)-statements, and Precautionary (P)-statements as labeling elements. Furthermore, the CLP Regulation will affect the notification of product information on hazardous products to poisons information centers (PICs). At this moment product notification widely varies in procedures and requirements across EU Member States. Article 45 of the CLP Regulation contains a provision stating that the EC will (by January 20, 2012) review the possibility of harmonizing product notification. The European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) is recognized as an important stakeholder. For cosmetic products, the new Cosmetics Regulation will directly implement a new procedure for electronic cosmetic product notification in all EU Member States. Both the CLP Regulation and the Cosmetics Regulation will develop their own product notification procedure within different time frames. Harmonization of notification procedures for both product groups, especially a common electronic format, would be most effective from a cost-benefit viewpoint and would be welcomed by PICs.

  11. Carbon capture and storage: a novel technique for reducing greenhouse gas emissions regulated by the European Union

    Directory of Open Access Journals (Sweden)

    Íñigo Sanz Rubiles

    2013-12-01

    Full Text Available This article deals with main aspects of a novel technique for carbon dioxide capture and storage released by large combustion plants. Since this novel technique has become essential for reducing greenhouse gas emissions, it has been regulated by the European Union through the Directive number 2009/31. Therefore, acknowledging relevant legal aspects for regulation, suchas: mandatory, exploration permits, storage among others, the focus has been pointed out on responsibilities and guarantees regime.

  12. Mitochondrial and nuclear DNA analysis of genetic heterogeneity among recruitment cohorts of the European flat oyster Ostrea edulis.

    Science.gov (United States)

    Taris, Nicolas; Boudry, Pierre; Bonhomme, François; Camara, Mark D; Lapègue, Sylvie

    2009-12-01

    Marine species with high fecundity and high early mortality may also have high variance in reproductive success among individuals due to stochastic factors, making successful reproduction a "sweepstakes." In some cases, the impact is sufficient to reduce the effective number of breeders in wild populations. We tested two predictions of the sweepstakes reproductive success hypothesis in a French Atlantic population of the European flat oyster, Ostrea edulis, by evaluating (1) whether individuals belonging to temporally discrete recruitment cohorts within a single reproductive season displayed reduced genetic variation relative to the entire adult population, and (2) whether these temporal cohorts of recruits were genetically differentiated from each other. We assayed genetic variation at four nuclear microsatellites and a 12S mitochondrial fragment in four recruitment cohorts. Nuclear markers provided no evidence for differentiation between recruitment cohorts and adults or between temporal cohorts. However, mitochondrial data indicate that the first temporal cohort showed significant differentiation with the last (Fst = 0.052, P < 0.05) and with the adult sample (Fst = 0.058, P < 0.05). These differences are most likely due to the smaller effective size of the mitochondrial genome-and hence its increased sensitivity to drift compared to the nuclear genome. This slight mitochondrial signal indicates a certain limitation in the number of contributing female parents in this species. The "sweepstakes" phenomenon was therefore limited in our case. Hypothetically, this phenomenon may occur or not, with a high variance as a result of the interaction between the oyster reproductive biology and different environmental conditions.

  13. THE PROFIT AND LOSS ACCOUNT THROUGH THE ROMANIAN ACCOUNTING REGULATIONS. FROM EUROPEAN TO INTERNATIONAL

    Directory of Open Access Journals (Sweden)

    MARIANA MAN

    2011-01-01

    Full Text Available The paper analyses the profit and loss account from the Romanian accounting regulations’ perspective in terms of format, structure, content, which is subject to the approval of OMPF no.3055/2009 harmonized with the European accounting directives. Even if from the name it appears the compliance with the European accounting directives, the Romanian profit and loss account brings elements from the international standard IAS1. Moreover, if we compare the structure of profit and loss account chosen by the Romanian policy makers with the structure proposed by the IV Directive, the list model, with the classification of operating expenses by nature, we conclude that they are similar, with small features found in the present order, an order which was also analyzed in the paper. We tried to explain and argue the preference of Romanian policy makers for the list model of profit and loss account, with the classification of expenses by nature, but also the necessity to present, in the explicative notes, the classification of expenses by purpose, which is actually a combination of regulations between the IV Directive and the IAS1 standard. In the second part of the paper we considered interesting to analyze the content of certain elements related to the profit and loss account, namely: the extraordinary elements, the cost of sold goods and services of the Analysis of operating result to capture both Romanian specific features, as well as the elements of IAS1 standard, the net turnover indicator, the items of gain and loss, the stocks variation element and the element Result on action.

  14. [Influence of European regulations on quality, safety and availability of cell and tissue allografts in Germany].

    Science.gov (United States)

    Pruss, A; von Versen, R

    2007-04-01

    The transplantation of allogenic tissue (bone, cartilage, tendon, skin, amnion and special preparations such as demineralised bone matrix and acellular dermis) is an important component of the treatment of bone and soft tissue defects, particularly in traumatology and orthopaedic, reconstructive and plastic surgery. In Germany, the requirement for such tissue transplants is met by supply from local tissue banks (in particular bone banks) and a small number of regional and national tissue banks. These banks operate on the basis of the "Guidelines for Bone Banks" laid down by the German Chamber of Physicians, and of the German Drug Law (AMG). The 2004/23/EG guidelines issued by the European Parliament and ratified on 31/3/2004 define the quality and safety standards for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. These guidelines will have a major impact on all aspects of tissue banking and transplantation. In particular, the new guidelines will remove the possibility for local tissue banks to operate outside of national drug laws ( section sign 4 a [4]). The currently in draft law on "Quality and Safety of Human Tissues and Cells" ("Tissue Law") of the Federal Health Ministry seems to be heading in this direction, but it also includes possibilities for the continuation of local banks. An additional European guideline draft "Proposal for the regulation of advanced therapeutic medical products" is currently under discussion. This paper assesses the impact of these new pieces of legislation on the quality, safety and availability of human cell and tissue transplants in terms of the current situation and future prospects in Germany.

  15. Comparison of regulations amongst various European countries; Comparaison des reglementations dans les differents pays d`europe

    Energy Technology Data Exchange (ETDEWEB)

    Cottard, E. [Cogen Europe (Country unknown/Code not available)

    1997-12-31

    The pollutant emission standards (mainly NOx and CO) at national and european levels for large combustion plants, turbines and engines, are reviewed and compared: Germany, Denmark, Holland, Italy and United Kingdom. Their impact and implementation methodology are discussed. The growing influence of regional and even local regulations such as the implementation of special protection zones, is shown

  16. The European Union's REACH regulation: a review of its history and requirements.

    Science.gov (United States)

    Williams, E Spencer; Panko, Julie; Paustenbach, Dennis J

    2009-01-01

    In 2006, the European Union (EU) promulgated a monumental regulatory initiative for the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH). To date, several thousand pages of text have been needed to describe the expectations of this regulation. There were numerous reasons for the promulgation of REACH, but, by and large, it is an extension of the global desire to produce fewer industrial chemicals, to understand the possible human and ecological hazards of those that are produced, and to insure that any major threat is anticipated, as well as prevented. Most industry-related groups consider it the most wide-ranging and costly regulatory initiatives related to health risk assessment ever to be promulgated. This review presents a description of REACH that should inform scientists, managers, and others about its objectives and the means to satisfy them. Registration is required for all chemicals manufactured or imported into the EU, unless specifically exempted. Registration is expected to be a collaborative process among companies, which will generate a dossier containing data on physicochemical characteristics, as well as toxicological and ecotoxicological properties. Though the magnitude of the gaps in the data required for registration is uncertain at this point, it is clear that basic toxicology testing will have to be conducted for many chemical substances that have not undergone formal review up to this point. For many chemicals, an examination of hazards and risks arising from the use of these substances will also be required in the form of a chemical safety report (CSR). Beginning with the dual processes of dossier and substance evaluation, the European Chemicals Agency (ECHA), the Member States of the EU, and the European Commission will identify chemicals that may pose unacceptable hazards to human health and/or the environment, and will curtail or restrict their usage. The implementation of REACH will expand and deepen the

  17. Impact of the changing European Union regulations on Estonian accounting policies. Euroopa finantsaruandluse muudatuste sobivus Eestis

    Directory of Open Access Journals (Sweden)

    Maret Güldenkoh

    2014-12-01

    Full Text Available Financial reporting and audit activities are the areas to ensure the legitimacy of the everyday economic activities of the accounting entities. Financial reporting provides information on the past periods of the accounting entities; the audit activity is used to verify the accuracy of the recorded information and an assessment is given to the financial position of the audited entities. Auditing of financial statements prepared on the basis of historical financial information, results in increased reliability of the economic environment and stability of the financial environment of the state. The objective of this research was to assess the suitability of the European Union reporting principles for the auditing activity in Estonia. This objective was achieved with the following research tasks: 1 to provide an overview of the legal framework of the EU financial reporting and auditing activities; 2 to assess the problems related to the transposition of the legal framework in Estonia. The article consists of two parts, the first part provides an overview of the regulation of financial reporting and auditing activities in the European Union. The second part assess the impact of the European Union legislation on financial reporting and audit activities for the activities of the corresponding areas in Estonia. The research method used was a combined method, in the course of which legal acts were collected and analyzed, analysis of the data obtained from the commercial register was carried out and the impact of the Directive 2013/34 / EC to the accounting area of Estonia was assessed. Upon application of the Directive 2013/34/EU to the Estonia's legal framework, one cannot be sure that the desired administrative burden is reduced, rather it could bring along growth of the administrative burden for the accounting entities, which comprises the obligation of submission of additional reporting to various authorities. The reporting process could become more

  18. Prospects for public participation on nuclear risks and policy options: innovations in governance practices for sustainable development in the European Union.

    Science.gov (United States)

    O'Connor, M; van den Hove, S

    2001-09-14

    We outline the potential participative governance and risk management in application to technological choices in the nuclear sector within the European Union (EU). Well-conducted public participation, stakeholder consultation and deliberation procedures can enhance the policy process and improve the robustness of strategies dealing with high-stakes investment and risk management challenges. Key nuclear issues now confronting EU member states are: public concern with large-scale environmental and health issues; the Chernobyl accident (and others less catastrophic) whose effect has been to erode public confidence and trust in the nuclear sector; the maturity of the nuclear plant, hence the emerging prominence of waste transportation, reprocessing and disposal issues as part of historical liability within the EU; the nuclear energy heritage of central and eastern European candidate countries to EU accession. The obligatory management of inherited technological risks and uncertainties on large temporal and geographical scales, is a novel feature of technology assessment and governance. Progress in the nuclear sector will aid the development of methodologies for technological foresight and risk governance in fields other than the nuclear alone.

  19. Identification of nuclear protein targets for six leukemogenic tyrosine kinases governed by post-translational regulation.

    Directory of Open Access Journals (Sweden)

    Andrew Pierce

    Full Text Available Mutated tyrosine kinases are associated with a number of different haematological malignancies including myeloproliferative disorders, lymphoma and acute myeloid leukaemia. The potential commonalities in the action of six of these leukemogenic proteins on nuclear proteins were investigated using systematic proteomic analysis. The effects on over 3600 nuclear proteins and 1500 phosphopeptide sites were relatively quantified in seven isogenic cell lines. The effects of the kinases were diverse although some commonalities were found. Comparison of the nuclear proteomic data with transcriptome data and cytoplasmic proteomic data indicated that the major changes are due to post-translational mechanisms rather than changes in mRNA or protein distribution. Analysis of the promoter regions of genes whose protein levels changed in response to the kinases showed the most common binding site found was that for NFκB whilst other sites such as those for the glucocorticoid receptor were also found. Glucocorticoid receptor levels and phosphorylation were decreased by all 6 PTKs. Whilst Glucocorticoid receptor action can potentiate NFκB action those proteins where genes have NFκB binding sites were in often regulated post-translationally. However all 6 PTKs showed evidence of NFkB pathway modulation via activation via altered IkB and NFKB levels. Validation of a common change was also undertaken with PMS2, a DNA mismatch repair protein. PMS2 nuclear levels were decreased in response to the expression of all 6 kinases, with no concomitant change in mRNA level or cytosolic protein level. Response to thioguanine, that requires the mismatch repair pathway, was modulated by all 6 oncogenic kinases. In summary common targets for 6 oncogenic PTKs have been found that are regulated by post-translational mechanisms. They represent potential new avenues for therapies but also demonstrate the post-translational regulation is a key target of leukaemogenic kinases.

  20. Nuclear receptor 4a3 (nr4a3 regulates murine mast cell responses and granule content.

    Directory of Open Access Journals (Sweden)

    Gianni Garcia-Faroldi

    Full Text Available Nuclear receptor 4a3 (Nr4a3 is a transcription factor implicated in various settings such as vascular biology and inflammation. We have recently shown that mast cells dramatically upregulate Nuclear receptor 4a3 upon activation, and here we investigated the functional impact of Nuclear receptor 4a3 on mast cell responses. We show that Nuclear receptor 4a3 is involved in the regulation of cytokine/chemokine secretion in mast cells following activation via the high affinity IgE receptor. Moreover, Nuclear receptor 4a3 negatively affects the transcript and protein levels of mast cell tryptase as well as the mast cell's responsiveness to allergen. Together, these findings identify Nuclear receptor 4a3 as a novel regulator of mast cell function.

  1. Peroxiredoxin 2 nuclear levels are regulated by circadian clock synchronization in human keratinocytes.

    Science.gov (United States)

    Avitabile, Daniele; Ranieri, Danilo; Nicolussi, Arianna; D'Inzeo, Sonia; Capriotti, Anna Laura; Genovese, Licia; Proietti, Sara; Cucina, Alessandra; Coppa, Anna; Samperi, Roberto; Bizzarri, Mariano; Laganà, Aldo; Torrisi, Maria Rosaria

    2014-08-01

    Circadian rhythms are highly conserved time tracking systems regulating important biological processes at both systemic and cellular levels. The present study was aimed to identify proteins and biological functions circadian regulated in human keratinocytes. HaCaT keratinocytes were entrained by temperature cycles, and a proteomic study was performed on cell fractions isolated under free running conditions at constant temperature. Bioinformatics analysis revealed that molecular clock entrainment was associated with changes in molecular components regulating cell proliferation, energy metabolism, transcription, translation and redox balance. Nuclear levels of the antioxidant enzyme Peroxiredoxin 2 (PRDX2) were found to oscillate rhythmically over two entire 24h long cycles. Donwregulation of PRDX2 resulted in upregulation of the mitochondrion-specific Peroxiredoxin 3 (PRDX3), all other members of the Peroxiredoxin family remained unaltered. Furthermore, PRDX2 knockdown increased intracellular levels of reactive oxygen species (ROS) and impaired cell cycle progression and proliferation. HaCaT cells transduced with a scramble shRNA were used as control. Our work is the first to show that nuclear levels of PRDX2 display circadian oscillation participating in the regulation of human keratinocytes redox balance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Prostaglandins regulate nuclear localization of Fascin and its function in nucleolar architecture.

    Science.gov (United States)

    Groen, Christopher M; Jayo, Asier; Parsons, Maddy; Tootle, Tina L

    2015-05-15

    Fascin, a highly conserved actin-bundling protein, localizes and functions at new cellular sites in both Drosophila and multiple mammalian cell types. During Drosophila follicle development, in addition to being cytoplasmic, Fascin is in the nuclei of the germline-derived nurse cells during stages 10B-12 (S10B-12) and at the nuclear periphery during stage 13 (S13). This localization is specific to Fascin, as other actin-binding proteins, Villin and Profilin, do not exhibit the same subcellular distribution. In addition, localization of fascin1 to the nucleus and nuclear periphery is observed in multiple mammalian cell types. Thus the regulation and function of Fascin at these new cellular locations is likely to be highly conserved. In Drosophila, loss of prostaglandin signaling causes a global reduction in nuclear Fascin and a failure to relocalize to the nuclear periphery. Alterations in nuclear Fascin levels result in defects in nucleolar morphology in both Drosophila follicles and cultured mammalian cells, suggesting that nuclear Fascin plays an important role in nucleolar architecture. Given the numerous roles of Fascin in development and disease, including cancer, our novel finding that Fascin has functions within the nucleus sheds new light on the potential roles of Fascin in these contexts. © 2015 Groen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression

    OpenAIRE

    Grund, S.E.; Fischer, Tomás; Cabal, G.G.; Antúnez Temporal, Oreto; Pérez Ortín, José Enrique; Hurt, E.

    2008-01-01

    Inner nuclear membrane proteins containing a LEM (LAP2, emerin, and MAN1) domain participate in different processes, including chromatin organization, gene expression, and nuclear envelope biogenesis. In this study, we identify a robust genetic interaction between transcription export (TREX) factors and yeast Src1, an integral inner nuclear membrane protein that is homologous to vertebrate LEM2. DNA macroarray analysis revealed that the expression of the phosphate-regulated genes PHO11 ,PHO12...

  4. Regulator of calcineurin 1 gene transcription is regulated by nuclear factor-kappaB.

    Science.gov (United States)

    Zheng, Lanlan; Liu, Heng; Wang, Pin; Song, Weihong; Sun, Xiulian

    2014-02-01

    Regulator of calcineurin 1 (RCAN1) has been implicated in pathogenesis of neurodegeneration and various cancers. Recently, we showed that RCAN1 expression was elevated in Down Syndrome and Alzheimer's disease and its expression transpose over induced neuronal apoptosis. As NF-κB is an important transcription factor involved in cell survival and RCAN1 played vital roles in cell viability, we examined whether NF-κB regulates RCAN1 gene expression. Our results here showed that the RCAN1 isoform 4 gene transcription can be activated by NF-κB signaling. NF-κB activated RCAN1 isoform 4 gene promoter. Luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation identified a NF-κB responsive element in the region of -576-554bp of the RCAN1 isoform 4 promoter. Activation of RCAN1 gene expression by NF-κB is independent from the calcineurin-NFAT signaling since the NF-κB responsive element was distinct from the NFAT binding sites that was previously identified in the region of -350-166bp. Indeed, activation of calcineurin-NFAT signaling decreased NF-κB transcriptional activity, while activation of NF-κB elevated NFAT transcriptional activity. RCAN1 isoform 4 gene transcription was repressed by its own protein expression in a negative feedback loop. Our findings about RCAN1 gene transcription regulated by NF-κB further supported the vital roles of RCAN1 in cellular functions and its involvement in AD pathogenesis.

  5. Transcriptional Regulation by Nuclear Corepressors and PGC-1α: Implications for Mitochondrial Quality Control and Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Zhengtang Qi

    2012-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs and estrogen-related receptor (ERRα are ligand-activated nuclear receptors that coordinately regulate gene expression. Recent evidence suggests that nuclear corepressors, NCoR, RIP140, and SMRT, repress nuclear receptors-mediated transcriptional activity on specific promoters, and thus regulate insulin sensitivity, adipogenesis, mitochondrial number, and activity in vivo. Moreover, the coactivator PGC-1α that increases mitochondrial biogenesis during exercise and calorie restriction directly regulates autophagy in skeletal muscle and mitophagy in the pathogenesis of Parkinson's disease. In this paper, we discuss the PGC-1α’s novel role in mitochondrial quality control and the role of nuclear corepressors in regulating insulin sensitivity and interacting with PGC-1α.

  6. Accumulation of nuclear ADAR2 regulates adenosine-to-inosine RNA editing during neuronal development.

    Science.gov (United States)

    Behm, Mikaela; Wahlstedt, Helene; Widmark, Albin; Eriksson, Maria; Öhman, Marie

    2017-02-15

    Adenosine to inosine (A-to-I) RNA editing is important for a functional brain, and most known sites that are subject to selective RNA editing have been found to result in diversified protein isoforms that are involved in neurotransmission. In the absence of the active editing enzymes ADAR1 or ADAR2 (also known as ADAR and ADARB1, respectively), mice fail to survive until adulthood. Nuclear A-to-I editing of neuronal transcripts is regulated during brain development, with low levels of editing in the embryo and a dramatic increase after birth. Yet, little is known about the mechanisms that regulate editing during development. Here, we demonstrate lower levels of ADAR2 in the nucleus of immature neurons than in mature neurons. We show that importin-α4 (encoded by Kpna3), which increases during neuronal maturation, interacts with ADAR2 and contributes to the editing efficiency by bringing it into the nucleus. Moreover, we detect an increased number of interactions between ADAR2 and the nuclear isomerase Pin1 as neurons mature, which contribute to ADAR2 protein stability. Together, these findings explain how the nuclear editing of substrates that are important for neuronal function can increase as the brain develops. © 2017. Published by The Company of Biologists Ltd.

  7. Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.

    Science.gov (United States)

    Raices, Marcela; Bukata, Lucas; Sakuma, Stephen; Borlido, Joana; Hernandez, Leanora S; Hart, Daniel O; D'Angelo, Maximiliano A

    2017-06-05

    Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. [Good for your health? An analysis of the requirements for scientific substantiation in European health claims regulation].

    Science.gov (United States)

    Todt, Oliver; Luján, José Luis

    2016-06-01

    To identify the various types of evidence, as well as their relative importance in European health claims regulation, in order to analyze the consequences for consumer protection of the requirements for scientific substantiation in this regulation. Qualitative analysis of various documents relevant to the regulatory process, particularly as to the implications of the standards of proof for the functional food market, as well as consumer behavior. European regulation defines a hierarchy of evidence that turns randomized controlled trials into a necessary and sufficient condition for health claim authorizations. Consumer protection can be interpreted in different manners. High standards of proof protect consumers from false information about the health outcomes of functional foods, while lower standards lead to more, albeit less accurate information about such outcomes being available to consumers.

  9. Good for your health? An analysis of the requirements for scientific substantiation in European health claims regulation

    Directory of Open Access Journals (Sweden)

    Oliver Todt

    2016-05-01

    Full Text Available Objective. To identify the various types of evidence, as well as their relative importance in European health claims regulation, in order to analyze the consequences for consumer protection of the requirements for scientific substantiation in this regulation. Materials and methods. Qualitative analysis of various documents relevant to the regulatory process, particularly as to the implications of the standards of proof for the functional food market, as well as consumer behavior. Results. European regulation defines a hierarchy of evidence that turns randomized controlled trials into a necessary and sufficient condition for health claim autho- rizations. Conclusions. Consumer protection can be interpreted in different manners. High standards of proof protect consumers from false information about the health outcomes of functional foods, while lower standards lead to more, albeit less accurate information about such outcomes being available to consumers.

  10. Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity

    Science.gov (United States)

    Shimamoto, Yuta; Tamura, Sachiko; Masumoto, Hiroshi; Maeshima, Kazuhiro

    2017-01-01

    Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. PMID:28428255

  11. Nuclear-cytoplasmic trafficking of NTF2, the nuclear import receptor for the RanGTPase, is subjected to regulation

    National Research Council Canada - National Science Library

    Chafe, Shawn C; Pierce, Jacqueline B; Mangroo, Dev

    2012-01-01

    .... Treatment of mammalian cells with polysorbitan monolaurate was found to inhibit nuclear export of tRNA and proteins, which are processes dependent on RanGTP in the nucleus, but not nuclear import...

  12. THE IMPACT OF NEW REGULATION ON FOUR EUROPEAN BANKING SYSTEMS. A BASEL III APPROACH

    Directory of Open Access Journals (Sweden)

    Anamaria AVADANEI

    2013-12-01

    Full Text Available One of the solutions designed to rebuild the banking system is the reconfiguration of the regulatory framework. Still active, the episodes of liquidity shortage and bank failure ask for solid measures in order to increase the solidity of individual institutions, to protect the financial stability of the banking systems and to maintain confidence on the markets. The aim of this paper is to analyze the situation of four European banking systems (Czech Republic, Poland, Romania and Croatia in terms of Basel III standards. Structured on three parts, the study points out the real concerns regarding Basel III effectiveness; analyzes the evolutions of capital, leverage and liquidity indicators and highlights the future possible scenarios/actions for aligning to the new regulation. To conclude, we determine the white and the black spots of the selected banking systems related to Basel III implementation. The results show good levels of capital in Poland, Czech Republic, Croatia and Romania, and some liquidity issues in Poland. The Czech and the Croatian banking systems are the best prepared for shocks.

  13. HIV-1 uncoating: connection to nuclear entry and regulation by host proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ambrose, Zandrea, E-mail: zaa4@pitt.edu [Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261 (United States); Aiken, Christopher [Department of Pathology, Microbiology and Immunology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

    2014-04-15

    The RNA genome of human immunodeficiency virus type 1 (HIV-1) is enclosed by a capsid shell that dissociates within the cell in a multistep process known as uncoating, which influences completion of reverse transcription of the viral genome. Double-stranded viral DNA is imported into the nucleus for integration into the host genome, a hallmark of retroviral infection. Reverse transcription, nuclear entry, and integration are coordinated by a capsid uncoating process that is regulated by cellular proteins. Although uncoating is not well understood, recent studies have revealed insights into the process, particularly with respect to nuclear import pathways and protection of the viral genome from DNA sensors. Understanding uncoating will be valuable toward developing novel antiretroviral therapies for HIV-infected individuals.

  14. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

    Directory of Open Access Journals (Sweden)

    Xiao-Su Zhao

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  15. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

    Science.gov (United States)

    Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  16. Nuclear receptor unfulfilled regulates axonal guidance and cell identity of Drosophila mushroom body neurons.

    Directory of Open Access Journals (Sweden)

    Suewei Lin

    Full Text Available Nuclear receptors (NRs comprise a family of ligand-regulated transcription factors that control diverse critical biological processes including various aspects of brain development. Eighteen NR genes exist in the Drosophila genome. To explore their roles in brain development, we knocked down individual NRs through the development of the mushroom bodies (MBs by targeted RNAi. Besides recapitulating the known MB phenotypes for three NRs, we found that unfulfilled (unf, an ortholog of human photoreceptor specific nuclear receptor (PNR, regulates axonal morphogenesis and neuronal subtype identity. The adult MBs develop through remodeling of gamma neurons plus de-novo elaboration of both alpha'/beta' and alpha/beta neurons. Notably, unf is largely dispensable for the initial elaboration of gamma neurons, but plays an essential role in their re-extension of axons after pruning during early metamorphosis. The subsequently derived MB neuron types also require unf for extension of axons beyond the terminus of the pruned bundle. Tracing single axons revealed misrouting rather than simple truncation. Further, silencing unf in single-cell clones elicited misguidance of axons in otherwise unperturbed MBs. Such axon guidance defects may occur as MB neurons partially lose their subtype identity, as evidenced by suppression of various MB subtype markers in unf knockdown MBs. In sum, unf governs axonal morphogenesis of multiple MB neuron types, possibly through regulating neuronal subtype identity.

  17. Nuclear Forensics International Technical Working Group (ITWG): a collaboration of scientists, law enforcement officials, and regulators working to combat nuclear terrorism and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Schwantes, Jon M.

    2013-10-25

    Founded in 1996 upon the initiative of the “Group of 8” governments (G8), the Nuclear Forensics International Technical Working Group (ITWG) is an ad hoc organization of official Nuclear Forensics practitioners (scientists, law enforcement, and regulators) that can be called upon to provide technical assistance to the global community in the event of a seizure of nuclear or radiological materials. The ITWG is supported by and is affiliated with nearly 40 countries and international partner organizations including the International Atomic Energy Agency (IAEA), EURATOM, INTERPOL, EUROPOL, and the United Nations Interregional Crime and Justice Research Institute (UNICRI) (Figure 1). Besides providing a network of nuclear forensics laboratories that are able to assist the global community during a nuclear smuggling event, the ITWG is also committed to the advancement of the science of nuclear forensic analysis, largely through participation in periodic table top and Collaborative Materials Exercises (CMXs). Exercise scenarios use “real world” samples with realistic forensics investigation time constraints and reporting requirements. These exercises are designed to promote best practices in the field and test, evaluate, and improve new technical capabilities, methods and techniques in order to advance the science of nuclear forensics. Past efforts to advance nuclear forensic science have also included scenarios that asked laboratories to adapt conventional forensics methods (e.g. DNA, fingerprints, tool marks, and document comparisons) for collecting and preserving evidence comingled with radioactive materials.

  18. Nuclear safeguards in the European Union carried out by the European Commission or: the EURATOM treaty. The unknown nature; Kernmaterialueberwachung in der Europaeischen Kommission oder: der EURATOM-Vertrag. Das unbekannte Wesen

    Energy Technology Data Exchange (ETDEWEB)

    Kilb, Wolfgang [European Commission, Luxembourg (Luxembourg). Generaldirektion Energie - EURATOM Kernmaterialueberwachung

    2016-03-15

    Nuclear safeguards in the 28 Member States of the European Union are based on a complex structure of national, supranational and international legal acts: A first approach are the three ''S'' to be met: security, safety, safeguards. The EURATOM safeguards are based on two pillars: the control of nuclear material itself, as well as different types of international agreements: the first refers to ''agreements with a third State'', the second on ''agreement with an international organization''.

  19. Stress-induced nuclear RNA degradation pathways regulate yeast bromodomain factor 2 to promote cell survival.

    Directory of Open Access Journals (Sweden)

    Kevin Roy

    2014-09-01

    Full Text Available Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2 is limited by spliceosome-mediated decay (SMD. Here we show that BDF2 is subject to an additional layer of post-transcriptional control through RNase III-mediated decay (RMD. We found that the yeast RNase III Rnt1p cleaves a stem-loop structure within the BDF2 mRNA to down-regulate its expression. However, these two nuclear RNA degradation pathways play distinct roles in the regulation of BDF2 expression, as we show that the RMD and SMD pathways of the BDF2 mRNA are differentially activated or repressed in specific environmental conditions. RMD is hyper-activated by salt stress and repressed by hydroxyurea-induced DNA damage while SMD is inactivated by salt stress and predominates during DNA damage. Mutations of cis-acting signals that control SMD and RMD rescue numerous growth defects of cells lacking Bdf1p, and show that SMD plays an important role in the DNA damage response. These results demonstrate that specific environmental conditions modulate nuclear RNA degradation pathways to control BDF2 expression and Bdf2p-mediated gene regulation. Moreover, these results show that precise dosage of Bromodomain factors is essential for cell survival in specific environmental conditions, emphasizing their importance for controlling chromatin structure and gene expression in response to environmental stress.

  20. Stress-Induced Nuclear RNA Degradation Pathways Regulate Yeast Bromodomain Factor 2 to Promote Cell Survival

    Science.gov (United States)

    Roy, Kevin; Chanfreau, Guillaume

    2014-01-01

    Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2) is limited by spliceosome-mediated decay (SMD). Here we show that BDF2 is subject to an additional layer of post-transcriptional control through RNase III-mediated decay (RMD). We found that the yeast RNase III Rnt1p cleaves a stem-loop structure within the BDF2 mRNA to down-regulate its expression. However, these two nuclear RNA degradation pathways play distinct roles in the regulation of BDF2 expression, as we show that the RMD and SMD pathways of the BDF2 mRNA are differentially activated or repressed in specific environmental conditions. RMD is hyper-activated by salt stress and repressed by hydroxyurea-induced DNA damage while SMD is inactivated by salt stress and predominates during DNA damage. Mutations of cis-acting signals that control SMD and RMD rescue numerous growth defects of cells lacking Bdf1p, and show that SMD plays an important role in the DNA damage response. These results demonstrate that specific environmental conditions modulate nuclear RNA degradation pathways to control BDF2 expression and Bdf2p-mediated gene regulation. Moreover, these results show that precise dosage of Bromodomain factors is essential for cell survival in specific environmental conditions, emphasizing their importance for controlling chromatin structure and gene expression in response to environmental stress. PMID:25232960

  1. Assisted suicide: Models of legal regulation in selected European countries and the case law of the European Court of Human Rights.

    Science.gov (United States)

    Grosse, Claudia; Grosse, Alexandra

    2015-10-01

    This paper presents three different models of the legal regulation of assisted suicide in European countries. First, the current legal regime governing assisted suicide in the Netherlands is described where both euthanasia and assisted suicide have been legalised. This section also includes some empirical data on euthanasia and assisted-suicide practices in the Netherlands, as well as a comparison with the current legal legislation in Belgium and Luxembourg. Next, Switzerland is presented as a country where euthanasia is punishable by law but assisted suicide is legally allowed, provided it is not carried out with selfish motives. This section also focuses on the assisted-suicide-related case law of the Swiss Federal Supreme Court and the European Court of Human Rights. Last, the current legal situation regarding assisted suicide in Austria and Germany is described. While the Austrian Penal Code explicitly prohibits assisted suicide, assistance with suicide is not specifically regulated by the German Penal Code. However, medical doctors are not allowed to assist suicides according to the professional codes of conduct drawn up by the German medical associations under the supervision of the health authorities. © The Author(s) 2014.

  2. Safety regulations of food and water implemented in the first year following the Fukushima nuclear accident

    Science.gov (United States)

    Hamada, Nobuyuki; Ogino, Haruyuki; Fujimichi, Yuki

    2012-01-01

    An earthquake and tsunami of historic proportions caused massive damage across the northeastern coast of Japan on the afternoon of 11 March 2011, and the release of radionuclides from the stricken reactors of the Fukushima nuclear power plant 1 was detected early on the next morning. High levels of radioiodines and radiocesiums were detected in the topsoil and plants on 15 March 2011, so sampling of food and water for monitoring surveys began on 16 March 2011. On 17 March 2011, provisional regulation values for radioiodine, radiocesiums, uranium, plutonium and other transuranic α emitters were set to regulate the safety of radioactively contaminated food and water. On 21 March 2011, the first restrictions on distribution and consumption of contaminated items were ordered. So far, tap water, raw milk, vegetables, mushrooms, fruit, nut, seaweeds, marine invertebrates, coastal fish, freshwater fish, beef, wild animal meat, brown rice, wheat, tea leaves and other foodstuffs had been contaminated above the provisional regulation values. The provisional regulation values for radioiodine were exceeded in samples taken from 16 March 2011 to 21 May 2011, and those for radiocesiums from 18 March 2011 to date. All restrictions were imposed within 318 days after the provisional regulation values were first exceeded for each item. This paper summarizes the policy for the execution of monitoring surveys and restrictions, and the outlines of the monitoring results of 220 411 samples and the enforced restrictions predicated on the information available as of 31 March 2012. PMID:22843368

  3. Nuclear Power Plants in central-eastern european countries; Gli impianti nucleari nei paesi dell'Europa centro-orientale

    Energy Technology Data Exchange (ETDEWEB)

    Righetti, Benito [Ambasciata d' Italia a Budapest, Budapest (Uruguay); Grimaldi, Alessandro [Universita' di Macerata, Macerata (Italy)

    2006-06-15

    The nuclear energy sources in Central-Eastern European Countries consist of 26 nuclear power plants that can give a large contribution to the EU energy provisioning security, supplying a reliable electricity network distribution at competitive generation cost. However, most of these power plants belong to old generation plants and are obsolescent. More generally nuclear safety, back-end of the fuel cycle and decommissioning are object of a wide-ranging negotiation. [Italian] Nei paesi dell'Europa Centro-Orientale sono presenti 26 reattori nucleari che possono dare un ampio contributo alla sicurezza energetica della UE, fornendo una rete di distribuzione di energia elettrica affidabile e a costi competitivi. Tuttavia, la maggior parte di questi impianti e' di vecchia generazione ed ormai obsoleta. Piu' in generale la sicurezza nucleare, la destinazione finale del combustibile esausto e la dismissione degli impianti sono oggetto di complessa negoziazione.

  4. Nuclear Energy in Western Europe: At the End of its Business Cycle? A review of policies in selected West European countries and Russia

    Energy Technology Data Exchange (ETDEWEB)

    Tangen, Kristian

    1997-12-31

    A series of seminars were held in Norway in 1995-97 focusing on nuclear energy policies, mainly in Europe. The key questions were: (1) What are the major driving forces behind the development of the nuclear industry?, and (2) Are we seeing the end of the nuclear energy era, or will we actually discover that the nuclear energy is moving towards its second blossom? This report summarizes the discussions at the seminars and discusses the above questions. The nature of the driving forces depends on the country in question. In France and Russia the nuclear sectors are large and prestigious and the course is difficult to change. In Germany and Sweden, political parties have adopted an anti-nuclear attitude and the issue is controversial, involving arguments both pro and con. The British nuclear sector has come to the end of the road. The main driving force has been the deregulation of the electricity market. In all countries, climate issues, independence from energy import, prestige and low costs have been arguments against close-downs. Massive expansion of nuclear power in Europe is unlikely. However, new plants might appear in Finland, Turkey or France. It is likely that technological development of the nuclear power sector, if any, will come in Asia. It is unclear whether this sector will benefit from climate issues. Renewable energy could become an important competitor if enough electricity could be produced. A state has been reached in which nuclear energy is both difficult to expand and to phase out. The nuclear energy issues are unlikely to affect the European gas market significantly. 53 refs., 10 refs., 13 tabs.

  5. Scientific Method and the Regulation of Health and Nutritional Claims by the European Food Safety Authority

    Science.gov (United States)

    Hoad, Darren

    2011-01-01

    The protection of European consumers from the false or misleading scientific and nutritional claims of food manufacturers took a step forward with the recent opinions of the European Food Safety Authority (EFSA). As a risk assessment agency, the EFSA recently assessed and rejected a vast number of food claim forcing the withdrawal of many claims…

  6. Regulating sustainable construction in Europe: An inquiry into the European Commission's harmonization attempts

    NARCIS (Netherlands)

    van der Heijden, J.; van Bueren, E.

    2013-01-01

    Purpose - The purpose of this paper is first, to gain insight into how the European member states have addressed the concept of sustainability in their building regulatory frameworks; and second, to gain insight in the effects of harmonization attempts of these frameworks by the European Commission

  7. Fostering Self-Regulated Learning through the European Language Portfolio: An Embedded Mixed Methods Study

    Science.gov (United States)

    Ziegler, Nicholas Allan

    2014-01-01

    The European Language Portfolio (ELP) is an alternative assessment used in foreign language classes throughout Europe to support and record language learning. Directly linked to the Common European Framework of Reference for Languages (Council of Europe, 2001) proficiency guidelines, it is designed to achieve an ambitious dual goal: document…

  8. Application of fault detection and identification (FDI) techniques in power regulating systems of nuclear reactors

    Science.gov (United States)

    Roy, K.; Banavar, R. N.; Thangasamy, S.

    1998-12-01

    Application of failure detection and identification (FDI) algorithms have essentially been limited to identification of a global fault in the system, and no further attempts have been made to locate subcomponent faults for root cause analysis. This paper presents Kalman filter-based methods for FDI in power regulating systems of nuclear reactors. The attempt here is to explain how the behavior of the states, residues, and covariances can be interpreted to identify subcomponent faults. An alternative to the Kalman filter-the risk-sensitive filter-is also introduced. Comparison of its performance with the Kalman filter-based FDI algorithms is studied. All simulation studies have been carried out on postulated faults in the power regulating system of heavy water moderated, low pressure vertical tank-type research reactors.

  9. Regulation of HIV-1 latency by chromatin structure and nuclear architecture.

    Science.gov (United States)

    Lusic, Marina; Giacca, Mauro

    2015-02-13

    Current antiretroviral therapies fail to cure HIV-1 (human immunodeficiency virus type 1) infection because HIV-1 persists as a transcriptionally inactive provirus in resting memory CD4(+) T cells. Multiple molecular events are known to regulate HIV-1 gene expression, yet the mechanisms governing the establishment and maintenance of latency remain incompletely understood. Here we summarize different molecular aspects of viral latency, from its establishment in resting CD4(+) T cells to the mechanisms involved in the reactivation of latent viral reservoirs. We focus on the relevance of chromatin structure and nuclear architecture in determining the transcriptional fate of integrated HIV-1 genomes, in light of recent findings indicating that proximity to specific subnuclear neighborhoods regulates HIV-1 gene expression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Radiological Impacts and Regulation of Rare Earth Elements in Non-Nuclear Energy Production

    Directory of Open Access Journals (Sweden)

    Timothy Ault

    2015-03-01

    Full Text Available Energy industries account for a significant portion of total rare earth usage, both in the US and worldwide. Rare earth minerals are frequently collocated with naturally occurring radioactive material, imparting an occupational radiological dose during recovery. This paper explores the extent to which rare earths are used by various non-nuclear energy industries and estimates the radiological dose which can be attributed to these industries on absolute and normalized scales. It was determined that typical rare earth mining results in an occupational collective dose of approximately 0.0061 person-mSv/t rare earth elements, amounting to a total of 330 person-mSv/year across all non-nuclear energy industries (about 60% of the annual collective dose from one pressurized water reactor operated in the US, although for rare earth mining the impact is spread out over many more workers. About half of the collective dose from non-nuclear energy production results from use of fuel cracking catalysts for oil refining, although given the extent of the oil industry, it is a small dose when normalized to the energy equivalent of the oil that is used annually. Another factor in energy industries’ reliance on rare earths is the complicated state of the regulation of naturally occurring radiological materials; correspondingly, this paper also explores regulatory and management implications.

  11. Control of metabolism by nutrient-regulated nuclear receptors acting in the brain.

    Science.gov (United States)

    Bantubungi, Kadiombo; Prawitt, Janne; Staels, Bart

    2012-07-01

    Today, we are witnessing a rising incidence of obesity worldwide. This increase is due to a sedentary life style, an increased caloric intake and a decrease in physical activity. Obesity contributes to the appearance of type 2 diabetes, dyslipidemia and cardiovascular complications due to atherosclerosis, and nephropathy. Therefore, the development of new therapeutic strategies may become a necessity. Given the metabolism controlling properties of nuclear receptors in peripheral organs (such as liver, adipose tissues, pancreas) and their implication in various processes underlying metabolic diseases, they constitute interesting therapeutic targets for obesity, dyslipidemia, cardiovascular disease and type 2 diabetes. The recent identification of the central nervous system as a player in the control of peripheral metabolism opens new avenues to our understanding of the pathophysiology of obesity and type 2 diabetes and potential novel ways to treat these diseases. While the metabolic functions of nuclear receptors in peripheral organs have been extensively investigated, little is known about their functions in the brain, in particular with respect to brain control of energy homeostasis. This review provides an overview of the relationships between nuclear receptors in the brain, mainly at the hypothalamic level, and the central regulation of energy homeostasis. In this context, we will particularly focus on the role of PPARα, PPARγ, LXR and Rev-erbα. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. The Swedish radiation protection institute's regulations and general advice on nuclear medicine; issued on April 28, 2000

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-04-01

    These regulations and general advice are applicable to nuclear medicine within human medical care. The regulations are also applicable to activities where radioactive substances are administered to individuals in connection to medical or biomedical research and medical examinations for insurance or legal purposes.

  13. 7SK small nuclear RNA transcription level down-regulates in human tumors and stem cells.

    Science.gov (United States)

    Abasi, Mozhgan; Bazi, Zahra; Mohammadi-Yeganeh, Samira; Soleimani, Masoud; Haghpanah, Vahid; Zargami, Nosratollah; Ghanbarian, Hossein

    2016-11-01

    The small nuclear noncoding RNA (snRNA) 7SK is a highly conserved noncoding RNA of 331 nucleotides in animals, which is present in a nuclear ribonucleoprotein complex with proteins such as methylphosphate capping enzyme (MePCE), hexamethylene bisacetamide-inducible proteins 1 and 2 (HEXIM1 and HEXIM2) and La-related protein 7 (Larp7). Regulating the activity of the positive transcription elongation factor b (P-TEFb) is the key function of 7SK noncoding RNA. Recently, we have shown that 7SK snRNA over-expression reduces human embryonic kidney 293T cell line viability. Here, we attempt to monitor the expression level of 7SK snRNA in different human cell lines and cancer tissues. Examination of 7SK transcription either in cell lines or in different malignant tissues including blood (CML), breast and colon showed that 7SK expression significantly down-regulated in cancer. Similar to human cancer tissues and cell lines, 7SK transcriptional level decreased in stem cells in comparison with differentiated cell types. In this regard, over-expression of 7SK snRNA might be a powerful tool for blocking cancer progression by controlling the activity of P-TEFb.

  14. Lipopolysaccharide triggers nuclear import of Lpcat1 to regulate inducible gene expression in lung epithelia.

    Science.gov (United States)

    Ellis, Bryon; Kaercher, Leah; Snavely, Courtney; Zhao, Yutong; Zou, Chunbin

    2012-07-26

    To report that Lpcat1 plays an important role in regulating lipopolysaccharide (LPS) inducible gene transcription. Gene expression in Murine Lung Epithelial MLE-12 cells with LPS treatment or Haemophilus influenza and Escherichia coli infection was analyzed by employing quantitative Reverse Transcription Polymerase Chain Reaction techniques. Nucleofection was used to deliver Lenti-viral system to express or knock down Lpcat1 in MLE cells. Subcellular protein fractionation and Western blotting were utilized to study Lpcat1 nuclear relocation. Lpcat1 translocates into the nucleus from the cytoplasm in murine lung epithelia (MLE) after LPS treatment. Haemophilus influenza and Escherichia coli, two LPS-containing pathogens that cause pneumonia, triggered Lpcat1 nuclear translocation from the cytoplasm. The LPS inducible gene expression profile was determined by quantitative reverse transcription polymerase chain reaction after silencing Lpcat1 or overexpression of the enzyme in MLE cells. We detected that 17 out of a total 38 screened genes were upregulated, 14 genes were suppressed, and 7 genes remained unchanged in LPS treated cells in comparison to controls. Knockdown of Lpcat1 by shRNA dramatically changed the spectrum of the LPS inducible gene transcription, as 18 genes out of 38 genes were upregulated, of which 20 genes were suppressed or unchanged. Notably, in Lpcat1 overexpressed cells, 25 genes out of 38 genes were reduced in the setting of LPS treatment. These observations suggest that Lpcat1 relocates into the nucleus in response to bacterial infection to differentially regulate gene transcriptional repression.

  15. Herbs and dietary supplements in the European Union: a review of the regulations with special focus on Germany and Poland.

    Science.gov (United States)

    Konik, Ewa A; Jungling, Roman C; Bauer, Brent A

    2011-03-01

    In the European Union, the manufacturing of and the trade in herbs and dietary supplements are regulated by pharmaceutical and food laws. While dietary supplements are subject to food laws, provisions dealing with herbs are primarily to be found in pharmaceutical regulations. Having a basic understanding of the complexities of this regulatory environment can help clinicians and their patients understand the unique challenges and opportunities presented by EU herbs and supplements and may help inform regulatory practices in other countries struggling to ensure quality and safety of such products.

  16. Investigating microRNA-mediated regulation of the nascent nuclear transcripts in plants: a bioinformatics workflow.

    Science.gov (United States)

    Yu, Dongliang; Tang, Zhonghai; Shao, Chaogang; Ma, Xiaoxia; Xiang, Taihe; Fan, Zhihong; Wang, Huizhong; Meng, Yijun

    2017-06-14

    Most of the microRNAs (miRNAs) play their regulatory roles through posttranscriptional target decay or translational inhibition. For both plants and animals, these regulatory events were previously considered to take place in cytoplasm, as mature miRNAs were observed to be exported to the cytoplasm for Argonaute (AGO) loading and subsequent target binding. Recently, this notion was challenged by increasing pieces of evidence in the animal cells that uncovered the nuclear importation and action of the AGO-associated miRNAs. The nuclear-localized regulatory mode was also reported for the plant miRNAs. However, evidence is still lacking to show the universality and conservation of the miRNA-mediated regulation in the plant nuclei. Here, we introduced a bioinformatics workflow for genome-wide investigation of miRNA-guided, cleavage-based regulation of the nascent nuclear transcripts. Facilitated by the tool package PmiRNTSA (Plant microRNA-mediated nascent transcript slicing analyzer), plant biologists could perform a comprehensive search for the miRNA slicing sites located within the introns or the exon-intron/intron-exon junctions of the target transcripts, which are supported by degradome sequencing data. The results enable the researchers to examine the co-transcriptional regulatory model of the miRNAs for a specific plant species. Moreover, a case study was performed to search for the slicing sites located within the exon-intron/intron-exon junctions in two model plants. A case study was performed to show the feasibility and reliability of our workflow. Together, we hope that this work could inspire much more innovative research efforts to expand the current understanding of the miRNA action modes in plants. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Mutations Affecting Light Regulation of Nuclear Genes Encoding Chloroplast Glyceraldehyde-3-Phosphate Dehydrogenase in Arabidopsis1

    Science.gov (United States)

    Chan, Chui Sien; Peng, Hsiao-Ping; Shih, Ming-Che

    2002-01-01

    Expression of nuclear genes that encode the A and B subunits of chloroplast glyceraldehyde-3-phosphate dehydrogenase (GAPA and GAPB) of Arabidopsis is known to be regulated by light. We used a negative selection approach to isolate mutants that were defective in light-regulated expression of the GAPA gene. Two dominant mutants belonging to the same complementation group, uga1-1 and uga1-2, were then characterized. These two mutants showed a dramatic reduction in GAPA mRNA level in both mature plants and seedlings. Surprisingly, mutations in uga1-1 and uga1-2 had no effect on the expression of GAPB and several other light-regulated genes. In addition, we found that the chloroplast glyceraldehyde-3-phosphate dehydrogenase enzyme activity of the mutants was only slightly lower than that of the wild type. Western-blot analysis showed that the GAPA protein level was nearly indistinguishable between the wild-type and the uga mutants. These results suggested that posttranscriptional control was involved in the up-regulation of the GAPA protein in the mutants. The uga1-1 mutation was mapped to the bottom arm of chromosome V of the Arabidopsis genome. PMID:12428012

  18. Mutations affecting light regulation of nuclear genes encoding chloroplast glyceraldehyde-3-phosphate dehydrogenase in Arabidopsis.

    Science.gov (United States)

    Chan, Chui Sien; Peng, Hsiao-Ping; Shih, Ming-Che

    2002-11-01

    Expression of nuclear genes that encode the A and B subunits of chloroplast glyceraldehyde-3-phosphate dehydrogenase (GAPA and GAPB) of Arabidopsis is known to be regulated by light. We used a negative selection approach to isolate mutants that were defective in light-regulated expression of the GAPA gene. Two dominant mutants belonging to the same complementation group, uga1-1 and uga1-2, were then characterized. These two mutants showed a dramatic reduction in GAPA mRNA level in both mature plants and seedlings. Surprisingly, mutations in uga1-1 and uga1-2 had no effect on the expression of GAPB and several other light-regulated genes. In addition, we found that the chloroplast glyceraldehyde-3-phosphate dehydrogenase enzyme activity of the mutants was only slightly lower than that of the wild type. Western-blot analysis showed that the GAPA protein level was nearly indistinguishable between the wild-type and the uga mutants. These results suggested that posttranscriptional control was involved in the up-regulation of the GAPA protein in the mutants. The uga1-1 mutation was mapped to the bottom arm of chromosome V of the Arabidopsis genome.

  19. TBLR1 regulates the expression of nuclear hormone receptor co-repressors

    Directory of Open Access Journals (Sweden)

    Brown Stuart

    2006-08-01

    Full Text Available Abstract Background Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. Results TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of

  20. Is the European medical products authorization regulation equipped to cope with the challenges of nanomedicines?

    NARCIS (Netherlands)

    Dorbeck-Jung, Barbel R.; Chowdhury, Nupur; Chowdhury, Nupur

    2011-01-01

    This article analyses the emerging European regulatory activities in relation to nanopharmaceuticals. The central question is whether the regulatory responses are appropriate to cope with the regulatory problems nanomedicinal development is posing. The article explores whether the medical product

  1. Salicylideneamino-2-thiophenol modulates nuclear factor-κB through redox regulation during the aging process.

    Science.gov (United States)

    Sung, Bokyung; Park, Seongjoon; Ha, Young Mi; Kim, Dae Hyun; Park, Chan Hum; Jung, Kyung Jin; Kim, Min Sun; Kim, You Jung; Kim, Mi Kyung; Moon, Jeon-Ok; Yokozawa, Takako; Kim, Nam Deuk; Yu, Byung Pal; Chung, Hae Young

    2015-02-01

    Many intracellular components have been implicated in the regulation of redox homeostasis, but homeostasis can be unbalanced by reactive species (RS), which also probably contribute to underlying inflammatory processes. Nuclear factor-κB (NF-κB) is a well-known redox-sensitive transcription factor that controls the genes responsible for regulating inflammation. In the present study, the authors investigated the effect of short-term salicylideneamino-2-thiophenol (SAL-2) administration on the modulation of pro-inflammatory NF-κB through redox regulation in aged rats. In addition, we compared the effects of SAL-2 and caloric restriction (CR) on inflammation and redox balance. The subjects were 24-month-old (old) Fischer 344 rats administered SAL-2 (10 mg/kg/day) by dietary supplementation or placed on a 30% restricted diet for 10 days, and 6-month-old (young) rats fed ad libitum for 10 days. We found that NF-κB activation and the expressions of its related genes (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cyclooxygenase-2 and inducible nitric oxide synthase) were suppressed by SAL-2 supplementation in old CR rats to the levels observed in young rats. In addition, our molecular studies showed that the inhibitory effect of SAL-2 on the activation of NF-κB was mediated by the ability of SAL-2 to block the nuclear translocations of cytosolic thioredoxin and redox factor-1. These findings strongly indicate that SAL-2 stabilizes age-related redox imbalance and modulates the signal transduction pathway involved in the age-associated molecular inflammatory process. © 2014 Japan Geriatrics Society.

  2. Two E2F elements regulate the proliferating cell nuclear antigen promoter differently during leaf development.

    Science.gov (United States)

    Egelkrout, Erin M; Mariconti, Luisa; Settlage, Sharon B; Cella, Rino; Robertson, Dominique; Hanley-Bowdoin, Linda

    2002-12-01

    E2F transcription factors regulate genes expressed at the G1/S boundary of the cell division cycle in higher eukaryotes. Although animal E2F proteins and their target promoters have been studied extensively, little is known about how these factors regulate plant promoters. An earlier study identified two E2F consensus binding sites in the promoter of a Nicotiana benthamiana gene encoding proliferating cell nuclear antigen (PCNA) and showed that the proximal element (E2F2) is required for the full repression of PCNA expression in mature leaves. In this study, we examined the distal element (E2F1) and how it interacts with the E2F2 site to regulate the PCNA promoter. Gel shift assays using plant nuclear extracts or purified Arabidopsis E2F and DP proteins showed that different complexes bind to the two E2F sites. Mutation of the E2F1 site or both sites differentially altered PCNA promoter function in transgenic plants. As reported previously for the E2F2 mutation, the E2F1 and E2F1+2 mutations partially relieved the repression of the PCNA promoter in mature leaves. In young tissues, the E2F1 mutation resulted in a threefold reduction in PCNA promoter activity, whereas the E2F1+2 mutation had no detectable effect. The activity of E2F1+2 mutants was indistinguishable from that of E2F2 mutants. These results demonstrate that both E2F elements contribute to the repression of the PCNA promoter in mature leaves, whereas the E2F1 site counters the repression activity of the E2F2 element in young leaves.

  3. Improved nuclear power plant operations and safety through performance-based safety regulation.

    Science.gov (United States)

    Golay, M W

    2000-01-07

    This paper illustrates some of the promise and needed future work for risk-informed, performance-based regulation (RIPBR). RIPBR is an evolving alternative to the current prescriptive method of nuclear safety regulation. Prescriptive regulation effectively constitutes a long, fragmented checklist of requirements that safety-related systems in a plant must satisfy. RIPBR, instead, concentrates upon satisfying negotiated performance goals and incentives for judging and rewarding licensee behavior to improve safety and reduce costs. In a project reported here, a case study was conducted concerning a pressurized water reactor (PWR) emergency diesel generator (EDG). Overall, this work has shown that the methods of RIPBR are feasible to use, and capable of justifying simultaneous safety and economic nuclear power improvements. However, it also reveals several areas where the framework of RIPBR should be strengthened. First, researchers need better data and understanding regarding individual component-failure modes that may cause components to fail. Not only are more data needed on failure rates, but more data and understanding are needed to enable analysts to evaluate whether these failures become more likely as the interval between tests is increased. This is because the current state of failure data is not sufficiently finely detailed to define the failure rates of individual component failure modes; such knowledge is needed when changing component-specific regulatory requirements. Second, the role of component testing, given that a component has failed, needs to be strengthened within the context of RIPBR. This includes formulating requirements for updating the prior probability distribution of a component failure rate and conducting additional or more frequent testing. Finally, as a means of compensating for unavoidable uncertainty as an obstacle to regulatory decision-making, limits to knowledge must be treated explicitly and formally. This treatment includes the

  4. THE PROFIT AND LOSS ACCOUNT THROUGH THE ROMANIAN ACCOUNTING REGULATIONS. FROM EUROPEAN TO INTERNATIONAL

    OpenAIRE

    MARIANA MAN; LIANA GĂDĂU

    2011-01-01

    The paper analyses the profit and loss account from the Romanian accounting regulations’ perspective in terms of format, structure, content, which is subject to the approval of OMPF no.3055/2009 harmonized with the European accounting directives. Even if from the name it appears the compliance with the European accounting directives, the Romanian profit and loss account brings elements from the international standard IAS1. Moreover, if we compare the structure of profit and loss account chose...

  5. Phylogeny and species delineation in European species of the genus Steganacarus (Acari, Oribatida) using mitochondrial and nuclear markers.

    Science.gov (United States)

    Kreipe, Victoria; Corral-Hernández, Elena; Scheu, Stefan; Schaefer, Ina; Maraun, Mark

    2015-06-01

    Species of the genus Steganacarus are soil-living oribatid mites (Acari, Phthiracaridae) with a ptychoid body. The phylogeny and species status of the species of Steganacarus are not resolved, some authors group all ten German species of Steganacarus within the genus Steganacarus whereas others split them into three subgenera, Steganacarus, Tropacarus and Atropacarus. Additionally, two species, S. magnus and T. carinatus, comprise morphotypes of questionable species status. We investigated the phylogeny and species status of ten European Steganacarus species, i.e. S. applicatus, S. herculeanus, S. magnus forma magna, S. magnus forma anomala, S. spinosus, Tropacarus brevipilus, T. carinatus forma carinata, T. carinatus forma pulcherrima, Atropacarus striculus and Rhacaplacarus ortizi. We used two molecular markers, a 251 bp fragment of the nuclear gene 28S rDNA (D3) and a 477 bp fragment of the mitochondrial COI region. The phylogeny based on a combined analysis of D3 and COI separated four subgenera (Steganacarus, Tropacarus and Atropacarus, Rhacaplacarus) indicating that they form monophyletic groups. The COI region separated all ten species of the genus Steganacarus and showed variation within some species often correlating with the geographic origin of the species. Resolution of the more conserved D3 region was limited, indicating that radiation events are rather recent. Overall, our results indicate that both genes alone cannot be used for phylogeny and barcoding since variation is too low in D3 and too high in COI. However, when used in combination these genes provide reliable insight into the phylogeny, radiation and species status of taxa of the genus Steganacarus.

  6. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Bucerius, Jan [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); University Hospital RWTH Aachen, RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center (MUMC), Department of Nuclear Medicine and Cardiovascular Research Institute (CARIM), P. Debyelaan 25, HX, Maastricht (Netherlands); Hyafil, Fabien [Bichat University Hospital, Inserm 1148, DHU FIRE, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Verberne, Hein J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands); University of Twente, Department of Biomedical Photonic Imaging, Faculty of Science and Technology, Enschede (Netherlands); Lindner, Oliver [Heart and Diabetes Center NRW, Nuclear Medicine and Molecular Imaging, Institute of Radiology, Bad Oeynhausen (Germany); Sciagra, Roberto [University of Florence, Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, Florence (Italy); Agostini, Denis [Normandie Universite, Department of Nuclear Medicine, CHU Cote de Nacre, Caen (France); Uebleis, Christopher [Ludwig-Maximilians Universitaet Muenchen, Department of Clinical Radiology, Muenchen (Germany); Gimelli, Alessia [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Hacker, Marcus [Medical University Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided therapy, Vienna (Austria); Collaboration: on behalf of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM)

    2016-04-15

    Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as ''strict guidelines'' but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards &apos

  7. Stimulus-dependent regulation of nuclear Ca2+ signaling in cardiomyocytes: a role of neuronal calcium sensor-1.

    Science.gov (United States)

    Nakao, Shu; Wakabayashi, Shigeo; Nakamura, Tomoe Y

    2015-01-01

    In cardiomyocytes, intracellular calcium (Ca2+) transients are elicited by electrical and receptor stimulations, leading to muscle contraction and gene expression, respectively. Although such elevations of Ca2+levels ([Ca2+]) also occur in the nucleus, the precise mechanism of nuclear [Ca2+] regulation during different kinds of stimuli, and its relationship with cytoplasmic [Ca2+] regulation are not fully understood. To address these issues, we used a new region-specific fluorescent protein-based Ca2+ indicator, GECO, together with the conventional probe Fluo-4 AM. We confirmed that nuclear Ca2+ transients were elicited by both electrical and receptor stimulations in neonatal mouse ventricular myocytes. Kinetic analysis revealed that electrical stimulation-elicited nuclear Ca2+ transients are slower than cytoplasmic Ca2+ transients, and chelating cytoplasmic Ca2+ abolished nuclear Ca2+ transients, suggesting that nuclear Ca2+ are mainly derived from the cytoplasm during electrical stimulation. On the other hand, receptor stimulation such as with insulin-like growth factor-1 (IGF-1) preferentially increased nuclear [Ca2+] compared to cytoplasmic [Ca2+]. Experiments using inhibitors revealed that electrical and receptor stimulation-elicited Ca2+ transients were mainly mediated by ryanodine receptors and inositol 1,4,5-trisphosphate receptors (IP3Rs), respectively, suggesting different mechanisms for the two signals. Furthermore, IGF-1-elicited nuclear Ca2+ transient amplitude was significantly lower in myocytes lacking neuronal Ca2+ sensor-1 (NCS-1), a Ca2+ binding protein implicated in IP3R-mediated pathway in the heart. Moreover, IGF-1 strengthened the interaction between NCS-1 and IP3R. These results suggest a novel mechanism for receptor stimulation-induced nuclear [Ca2+] regulation mediated by IP3R and NCS-1 that may further fine-tune cardiac Ca2+ signal regulation.

  8. Orphan nuclear receptor ERRγ is a key regulator of human fibrinogen gene expression

    Science.gov (United States)

    Zhang, Yaochen; Kim, Don-Kyu; Lu, Yan; Jung, Yoon Seok; Lee, Ji-min; Kim, Young-Hoon; Lee, Yong Soo; Kim, Jina; Dewidar, Bedair; Jeong, Won-IL; Lee, In-Kyu; Cho, Sung Jin; Dooley, Steven; Lee, Chul-Ho; Li, Xiaoying

    2017-01-01

    Fibrinogen, 1 of 13 coagulation factors responsible for normal blood clotting, is synthesized by hepatocytes. Detailed roles of the orphan nuclear receptors regulating fibrinogen gene expression have not yet been fully elucidated. Here, we identified estrogen-related receptor gamma (ERRγ) as a novel transcriptional regulator of human fibrinogen gene expression. Overexpression of ERRγ specially increased fibrinogen expression in human hepatoma cell line. Cannabinoid receptor types 1(CB1R) agonist arachidonyl-2'-chloroethylamide (ACEA) up-regulated transcription of fibrinogen via induction of ERRγ, whereas knockdown of ERRγ attenuated fibrinogen expression. Deletion analyses of the fibrinogen γ (FGG) gene promoter and ChIP assays revealed binding sites of ERRγ on human fibrinogen γ gene promoter. Moreover, overexpression of ERRγ was sufficient to increase fibrinogen gene expression, whereas treatment with GSK5182, a selective inverse agonist of ERRγ led to its attenuation in cell culture. Finally, fibrinogen and ERRγ gene expression were elevated in liver tissue of obese patients suggesting a conservation of this mechanism. Overall, this study elucidates a molecular mechanism linking CB1R signaling, ERRγ expression and fibrinogen gene transcription. GSK5182 may have therapeutic potential to treat hyperfibrinogenemia. PMID:28750085

  9. Workshop on environmental assessment. [Regulation of applications of nuclear energy and related ancillary systems

    Energy Technology Data Exchange (ETDEWEB)

    Watson, E.C. (comp.)

    1982-07-01

    Objectives of the workshop were: to review and evaluate the state-of-the-art of environmental impact assessments as applied to the regulation of applications of nuclear energy and related ancillary systems; to identify areas where existing technology allows establishing acceptable methods or standard practices that will meet the requirements of the NRC regulations, standards and guides for both normal operations and off-standard conditions including accident considerations; to illuminate topics where existing models or analytical methods are deficient because of unverified assumptions, a paucity of empirical data, conflicting results reported in the literature or a need for observation of operation systems; to compile, analyze and synthesize a prioritized set of research needs to advance the state-of-the-art to the level which will meet all of the requirements of the Commission's regulations, standards and guides; and to develop bases for maintaining the core of regulatory guidance at the optimum level balancing technical capabilities with practical considerations of cost and value to the regulatory process. The discussion held in small group sessions on aquatic, atmospheric, and terrestrial pathways are presented. The following research needs were identified as common to all three groups: validation of models; characterization of source terms; development of screening techniques; basis for de minimis levels of contamination; and updating of objectives for environmental monitoring programs.

  10. Dynamic regulation of nuclear architecture and mechanics—a rheostatic role for the nucleus in tailoring cellular mechanosensitivity

    Science.gov (United States)

    Lee, David A.

    2017-01-01

    ABSTRACT Nuclear architecture, a function of both chromatin and nucleoskeleton structure, is known to change with stem cell differentiation and differs between various somatic cell types. These changes in nuclear architecture are associated with the regulation of gene expression and genome function in a cell-type specific manner. Biophysical stimuli are known effectors of differentiation and also elicit stimuli-specific changes in nuclear architecture. This occurs via the process of mechanotransduction whereby extracellular mechanical forces activate several well characterized signaling cascades of cytoplasmic origin, and potentially some recently elucidated signaling cascades originating in the nucleus. Recent work has demonstrated changes in nuclear mechanics both with pluripotency state in embryonic stem cells, and with differentiation progression in adult mesenchymal stem cells. This review explores the interplay between cytoplasmic and nuclear mechanosensitivity, highlighting a role for the nucleus as a rheostat in tuning the cellular mechano-response. PMID:28152338

  11. Co-operation agreement between the European Organization for Nuclear Research (CERN) and the Government of People's Republic of Bangladesh concerning Education, Scientific and Technical Co-operation in High-Energy Physics

    CERN Document Server

    2014-01-01

    Co-operation agreement between the European Organization for Nuclear Research (CERN) and the Government of People's Republic of Bangladesh concerning Education, Scientific and Technical Co-operation in High-Energy Physics

  12. Co-operation Agreement between the European Organization for Nuclear Research (CERN) and King Abdulaziz City for Science and Technology (KACST) on behalf of the Government of the Kingdom of Saudi Arab

    CERN Document Server

    2005-01-01

    Co-operation Agreement between the European Organization for Nuclear Research (CERN) and King Abdulaziz City for Science and Technology (KACST) on behalf of the Government of the Kingdom of Saudi Arab

  13. Cooperation Agreement between the European Organization for Nuclear Research (CERN) and The Qatar Foundation for Education, Science and Community Development concerning Scientific and Technical Co-operation in High Energy Physics

    CERN Document Server

    2016-01-01

    Cooperation Agreement between the European Organization for Nuclear Research (CERN) and The Qatar Foundation for Education, Science and Community Development concerning Scientific and Technical Co-operation in High Energy Physics

  14. Supplementary agreement prolonging the agreement constituting a council of representatives of European states for d planning an international laboratory and organizing other forms of co-operation in nuclear research; Paris, 30th June 1953

    CERN Document Server

    CERN. Geneva

    1953-01-01

    Supplementary agreement prolonging the agreement constituting a council of representatives of European states for d planning an international laboratory and organizing other forms of co-operation in nuclear research; Paris, 30th June 1953

  15. Speech to be delivered by Mr. François de Rose, president of Council of the european organization for nuclear research on the occasion of the inauguration of the CERN proton synchrotron on 5 february 1960

    CERN Multimedia

    CERN Press Office. Geneva

    1960-01-01

    Speech to be delivered by Mr. François de Rose, president of Council of the european organization for nuclear research on the occasion of the inauguration of the CERN proton synchrotron on 5 february 1960

  16. Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Erika Guimarães

    Full Text Available Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10. In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.

  17. Advancing the 3Rs in Regulatory Toxicology - Carcinogenicity Testing: Scope for Harmonisation and Advancing the 3Rs in Regulated Sectors of the European Union

    Science.gov (United States)

    Abstract Different government agencies operating in the European Union regulate different types of chemical products, but all require testing for carcinogenicity to support applications for product marketing and commercialisation. A conference was held in Brussels in 2013 where ...

  18. Capsaicinoids improve egg production by regulating ovary nuclear transcription factors against heat stress in quail.

    Science.gov (United States)

    Sahin, N; Orhan, C; Tuzcu, M; Juturu, V; Sahin, K

    2017-04-01

    1. To examine the molecular mechanism of capsaicinoid supplementation from capsicum extract, laying Japanese quail (n = 180, 5 weeks old) were reared either at 22°C for 24 h/d (thermoneutral, TN) or at 34°C for 8 h/d (heat stress, HS) and fed on one of three diets containing 0, 25 or 50 mg of capsaicinoids per kilogram for 12 weeks (2 × 3 factorial arrangement). 2. The results revealed that exposure to HS decreased feed consumption by 10.7% and egg production by 13.6%, increased serum and ovary malondialdehyde (MDA) levels by 66.9% and 88.1%, respectively, and reduced ovary superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities by 28.3%, 48.7% and 43.8%, respectively. 3. There were magnifications in the ovary nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) levels by 42.4% and suppressions in nuclear factor (erythroid-derived 2)-like 2 (Nrf2), protein kinase B (Akt) and haem-oxygenase 1 (HO-1) levels by 29.2%, 38.2% and 30.7%, respectively, in heat-stressed quail. 4. With increasing supplemental capsaicinoids, there were linear increases in egg production, antioxidant enzyme activity, linear decreases in ovary MDA and NF-κB levels and linear increases in ovary Nrf2, Akt and HO-1 levels at a greater extent in quail reared under TN condition than those reared under HS condition. Two-way treatment interactions showed that the degree of restorations in all response variables was more notable under the HS environment than under the TN environment as supplemental capsaicinoid level was increased. 5. In conclusion, capsaicinoid supplementation alleviates oxidative stress through regulating the ovary nuclear transcription factors in heat-stressed quail.

  19. Cross-regulation of protein stability by p53 and nuclear receptor SHP.

    Directory of Open Access Journals (Sweden)

    Zhihong Yang

    Full Text Available We report here a novel interplay between tumor suppressor p53 and nuclear receptor SHP that controls p53 and SHP stability. Overexpression of p53 causes rapid SHP protein degradation, which does not require the presence of Mdm2 and is mediated by the proteosome pathway. Overexpressing SHP alone does not affect p53 stability. However, SHP destabilizes p53 by augmentation of Mdm2 ubiquitin ligase activity toward p53. The single amino acid substitution in the SHP protein SHPK170R increases SHP binding to p53 relative to SHP wild-type, whereas SHPG171A variant shows a diminished p53 binding. As a result of the cross-regulation, the tumor suppressor function of p53 and SHP in inhibition of colon cancer growth is compromised. Our findings reveal a unique scenario for a cross-inhibition between two tumor suppressors to keep their expression and function in check.

  20. Global harmonization of food safety regulations: perspectives from Japan after the Fukushima nuclear accident.

    Science.gov (United States)

    Yoshida, Mitsuru

    2014-08-01

    Japanese food self-sufficiency was only 39% on the basis of kcal in 2012, so Japan relies heavily on imported food. Hence the necessity of having international rules on the regulation of food contaminants is important especially for countries like Japan that depend on food imports. A One-Stop-Testing system is desired, in which the test result obtained from a single testing laboratory is accepted as valid worldwide. To establish this system, laboratory accreditation under international standards is a necessary step. Furthermore, the importance of supply of reference materials for internal quality control and proficiency testing for external quality control of each laboratory's analytical system is reviewed in connection with the experience of radioactive nuclide contamination resulting from the Fukushima nuclear power plant accident in March 2011. © 2013 Society of Chemical Industry.

  1. Emerging roles of orphan nuclear receptors in regulation of innate immunity.

    Science.gov (United States)

    Jin, Hyo Sun; Kim, Tae Sung; Jo, Eun-Kyeong

    2016-11-01

    Innate immunity constitutes the first line of defense against pathogenic and dangerous insults. However, it is a double-edged sword, as it functions in both clearance of infection and inflammatory damage. It is therefore important that innate immune responses are tightly controlled to prevent harmful excessive inflammation. Nuclear receptors (NRs) are a family of transcription factors that play critical roles in various physiological responses. Orphan NRs are a subset of NRs for which the ligands and functions are unclear. Accumulating evidence has revealed that orphan NRs play essential roles in innate immune responses to prevent pathogenic inflammatory responses and to enhance antimicrobial host defenses. In this review, we describe current knowledge on the roles and mechanisms of orphan NRs in the regulation of innate immune responses. Discovery of new functions of orphan NRs would facilitate development of novel preventive and therapeutic strategies against human inflammatory diseases.

  2. Styles of nuclear regulation and their consequences; Stile der Aufsicht ueber die Kerntechnik und ihre Folgen

    Energy Technology Data Exchange (ETDEWEB)

    Wilpert, B. [Technische Univ. Berlin (DE). Forschungsstelle Systemsicherheit (FSS)

    2005-03-01

    This contribution is about the document published as 'Announcement of the Basic Principles of Safety Management Systems in Nuclear Power Plants' in the Federal Gazette (Bundesanzeiger) by the German Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU) on July 27, 2004. A kind of checklist contains requirements to be taken into account as 'boundary conditions' in the implementation of safety management systems. In fact, every sentence in the document begins with a 'must' provision. Remarkably enough, these 'Basic Principles' were promulgated by the Ministry without any consultation with advisory bodies, such as the Advisory Committee on Reactor Safeguards (RSK), or organizations of plant operators. The paper contains much that is worth considering, but also many truisms. This article was written because of the way in which the document had been prepared and publicized. An effort is made in this article to generate some understanding of the consequences, in terms of labor psychology and organizational psychology, of the different approaches pursued by regulatory authorities. A key point in this respect is the fundamental difference it makes whether regulations (reglementations) by supervisory authorities address the design of technical components or human behavior. In the former case, precise criteria without any constraints can serve the purpose. Behavioral rules, on the other hand, need a certain measure of flexibility, also in the way mistakes are handled, in order to avoid negative reactions on the part of those concerned. (orig.)

  3. Rhythmic expressed clock regulates the transcription of proliferating cellular nuclear antigen in teleost retina.

    Science.gov (United States)

    Song, Hang; Wang, Defeng; De Jesus Perez, Felipe; Xie, Rongrong; Liu, Zhipeng; Chen, Chun-Chun; Yu, Meijuan; Yuan, Liudi; Fernald, Russell D; Zhao, Sheng

    2017-07-01

    Teleost fish continues to grow their eyes throughout life with the body size. In Astatotilapia burtoni, the fish retina increases by adding new retinal cells at the ciliary marginal zone (CMZ) and in the outer nuclear layer (ONL). Cell proliferation at both sites exhibits a daily rhythm in number of dividing cells. To understand how this diurnal rhythm of new cell production is controlled in retinal progenitor cells, we studied the transcription pattern of clock genes in retina, including clock1a, clock1b, bmal1a (brain and muscle ARNT-Like), and per1b (period1b). We found that these genes have a strong diurnal rhythmic transcription during light-dark cycles but not in constant darkness. An oscillation in pcna transcription was also observed during light-dark cycles, but again not in constant darkness. Our results also indicate an association between Clock proteins and the upstream region of pcna (proliferating cellular nuclear antigen) gene. A luciferase reporter assay conducted in an inducible clock knockdown cell line further demonstrated that the mutation on predicted E-Boxes in pcna promoter region significantly attenuated the transcriptional activation induced by Clock protein. These results suggested that the diurnal rhythmic expression of clock genes in A. burtoni retina could be light dependent and might contribute to the daily regulation of the proliferation of the retina progenitors through key components of cell cycle machinery, for instance, pcna. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Cytoplasmic and Nuclear TAZ Exert Distinct Functions in Regulating Primed Pluripotency

    Directory of Open Access Journals (Sweden)

    Xingliang Zhou

    2017-09-01

    Full Text Available Mouse epiblast stem cells (mEpiSCs and human embryonic stem cells (hESCs are primed pluripotent stem cells whose self-renewal can be maintained through cytoplasmic stabilization and retention of β-catenin. The underlying mechanism, however, remains largely unknown. Here, we show that cytoplasmic β-catenin interacts with and retains TAZ, a Hippo pathway effector, in the cytoplasm. Cytoplasmic retention of TAZ promotes mEpiSC self-renewal in the absence of nuclear β-catenin, whereas nuclear translocation of TAZ induces mEpiSC differentiation. TAZ is dispensable for naive mouse embryonic stem cell (mESC self-renewal but required for the proper conversion of mESCs to mEpiSCs. The self-renewal of hESCs, like that of mEpiSCs, can also be maintained through the cytoplasmic retention of β-catenin and TAZ. Our study indicates that how TAZ regulates cell fate depends on not only the cell type but also its subcellular localization.

  5. Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation.

    Science.gov (United States)

    Kieffer-Kwon, Kyong-Rim; Nimura, Keisuke; Rao, Suhas S P; Xu, Jianliang; Jung, Seolkyoung; Pekowska, Aleksandra; Dose, Marei; Stevens, Evan; Mathe, Ewy; Dong, Peng; Huang, Su-Chen; Ricci, Maria Aurelia; Baranello, Laura; Zheng, Ying; Tomassoni Ardori, Francesco; Resch, Wolfgang; Stavreva, Diana; Nelson, Steevenson; McAndrew, Michael; Casellas, Adriel; Finn, Elizabeth; Gregory, Charles; St Hilaire, Brian Glenn; Johnson, Steven M; Dubois, Wendy; Cosma, Maria Pia; Batchelor, Eric; Levens, David; Phair, Robert D; Misteli, Tom; Tessarollo, Lino; Hager, Gordon; Lakadamyali, Melike; Liu, Zhe; Floer, Monique; Shroff, Hari; Aiden, Erez Lieberman; Casellas, Rafael

    2017-08-17

    50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input. Single-molecule imaging shows that this step lowers transcription factor residence time and non-specific collisions during sampling for DNA targets. Third, chromatin interactions shift from long range to predominantly short range, and CTCF-mediated loops and contact domains double in numbers. This architectural change facilitates cognate promoter-enhancer contacts and also requires Myc and continual ATP production. Our results thus define the nature and transcriptional impact of chromatin decondensation and reveal an unexpected role for Myc in the establishment of nuclear topology in mammalian cells. Published by Elsevier Inc.

  6. PRESENT AND FUTURE OF NATIONAL ACCOUNTING REGULATIONS COMPLIANT WITH EUROPEAN DIRECTIVES

    Directory of Open Access Journals (Sweden)

    Dorina, LUȚĂ

    2014-11-01

    Full Text Available Financial statements are the basic form to submit accounting information and they envisage the provision of information on an enterprise's financial status, performance and cash flow. The quality of financial reporting arises from accounting norms that impose a joint terminology ensuring accounting information's comparability, communication and understanding. In the European Union, the standards adopted by the Council of European Communities aim at harmonizing accounting systems, preparing and submitting annual financial statements. To apply them, member states must first incorporate them into their own legislations resorting over time to various implementation solutions, which involves certain difficulties due to economic, social and political peculiarities. In this respect, the European Parliament has adopted Directive 2013/34/EU regarding annual financial statements, consolidated financial statements and associated reports of various types of enterprises. The present paper envisages a comparative study of old directives (Fourth Directive and Seventh Directive and the new Directive.

  7. Sharing killed the AVMSD star: the impossibility of European audiovisual media regulation in the era of the sharing economy

    Directory of Open Access Journals (Sweden)

    Indrek Ibrus

    2016-06-01

    Full Text Available The paper focuses on the challenges that the ‘sharing economy’ presents to the updating of the European Union’s (EU Audiovisual Media Service Directive (AVMSD, part of the broader Digital Single Market (DSM strategy of the EU. It suggests that the convergence of media markets and the emergence of video-sharing platforms may make the existing regulative tradition obsolete. It demonstrates an emergent need for regulatory convergence – AVMSD to create equal terms for all technical forms of content distribution. It then shows how the operational logic of video-sharing platforms undermines the AVMSD logic aimed at creating demand for professionally produced European content – leading potentially to the liberalisation of the EU audiovisual services market. Lastly, it argues that the DSM strategy combined with sharing-related network effects may facilitate the evolution of the oligopolistic structure in the EU audiovisual market, potentially harmful for cultural diversity.

  8. Best practices in performing flow cytometry in a regulated environment: feedback from experience within the European Bioanalysis Forum.

    Science.gov (United States)

    der Strate, Barry van; Longdin, Robin; Geerlings, Marie; Bachmayer, Nora; Cavallin, Maria; Litwin, Virginia; Patel, Minesh; Passe-Coutrin, Wilfried; Schoelch, Corinna; Companjen, Arjen; Fjording, Marianne Scheel

    2017-08-01

    Flow cytometry is a powerful tool that can be used for the support of (pre)clinical studies. Although various white papers are available that describe the set-up and validation of the instrumentation (the flow cytometer) and validation of flow cytometry methods, to date no guidelines exist that address the requirements for performing flow cytometry in a regulated environment. In this manuscript, the European Bioanalysis Forum presents additional practice guidance on the use of flow cytometry in the support of drug development programs and addresses areas that are not covered in the previous publications. The concepts presented here are based on the consensus of discussions in the European Bioanalysis Forum Topic Team 32, in meetings in Barcelona, Limelette and multiple telephone conferences.

  9. Highlights Lecture of the European Association of Nuclear Medicine and the World Federation of Nuclear Medicine and Biology Congress, Berlin 1998. Where next and how?

    Energy Technology Data Exchange (ETDEWEB)

    Britton, K.E. [Department of Nuclear Medicine, St. Bartholomew`s Hospital, London (United Kingdom)

    1998-12-01

    Nuclear medicine benefits not only the people of developed countries but also those who are in developing or deteriorating countries. The combination of diagnostic imaging, tissue characterisation, function measurement and targeted therapy is powerful and cost-effective. This congress provides a sample of nuclear medicine`s contribution to the world. (orig.) With 12 figs., 13 tabs., 20 refs.

  10. Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation.

    Science.gov (United States)

    Strzalka, Wojciech; Ziemienowicz, Alicja

    2011-05-01

    PCNA (proliferating cell nuclear antigen) has been found in the nuclei of yeast, plant and animal cells that undergo cell division, suggesting a function in cell cycle regulation and/or DNA replication. It subsequently became clear that PCNA also played a role in other processes involving the cell genome. This review discusses eukaryotic PCNA, with an emphasis on plant PCNA, in terms of the protein structure and its biochemical properties as well as gene structure, organization, expression and function. PCNA exerts a tripartite function by operating as (1) a sliding clamp during DNA synthesis, (2) a polymerase switch factor and (3) a recruitment factor. Most of its functions are mediated by its interactions with various proteins involved in DNA synthesis, repair and recombination as well as in regulation of the cell cycle and chromatid cohesion. Moreover, post-translational modifications of PCNA play a key role in regulation of its functions. Finally, a phylogenetic comparison of PCNA genes suggests that the multi-functionality observed in most species is a product of evolution. Most plant PCNAs exhibit features similar to those found for PCNAs of other eukaryotes. Similarities include: (1) a trimeric ring structure of the PCNA sliding clamp, (2) the involvement of PCNA in DNA replication and repair, (3) the ability to stimulate the activity of DNA polymerase δ and (4) the ability to interact with p21, a regulator of the cell cycle. However, many plant genomes seem to contain the second, probably functional, copy of the PCNA gene, in contrast to PCNA pseudogenes that are found in mammalian genomes.

  11. How do we avoid disaster when exiting the European Medicines Agency? Making the most of Brexit in pharmaceutical regulation.

    Science.gov (United States)

    Hatswell, Anthony James

    2017-01-01

    As the UK prepares to leave the EU, it must decide what path it is to take with a large number of regulatory and technical agencies who provide collaboration at the European level. In the case of pharmaceuticals, the European Medicines Agency (EMA) provides pan-European licencing for novel pharmaceuticals. Should the UK depart from the EMA system, this article highlights the loss to patients immediately (slower access to novel treatments), and in the long term by having no access to some novel products as companies choose not to launch in the UK. The lack of access then may also preclude the access to these treatments as generic medicines, causing harm far into the future. The other costs considered are the cost for duplicating the functions of the EMA, or the alternative of using the decisions of other regulators without input to decisions made. An alternative is then set out, of how the UK can prosper under 'Brexit', by remaining a member of the EMA, but accepting the decisions without political oversight (as currently happens with the European Commission). Additional freedom could be given to a UK regulator to accept decisions (where appropriate) from other agencies such as the Food & Drug Administration-further speeding access and making the UK a more attractive market. Such an arrangement would put the UK in a better position than the good position it is in currently. This would give patients (both now and in the future) the best access to treatment possible, and promote/attract an industry which employs (directly and indirectly) 500,000 jobs.

  12. How do we avoid disaster when exiting the European Medicines Agency? Making the most of Brexit in pharmaceutical regulation

    Science.gov (United States)

    Hatswell, Anthony James

    2017-01-01

    As the UK prepares to leave the EU, it must decide what path it is to take with a large number of regulatory and technical agencies who provide collaboration at the European level. In the case of pharmaceuticals, the European Medicines Agency (EMA) provides pan-European licencing for novel pharmaceuticals. Should the UK depart from the EMA system, this article highlights the loss to patients immediately (slower access to novel treatments), and in the long term by having no access to some novel products as companies choose not to launch in the UK. The lack of access then may also preclude the access to these treatments as generic medicines, causing harm far into the future. The other costs considered are the cost for duplicating the functions of the EMA, or the alternative of using the decisions of other regulators without input to decisions made. An alternative is then set out, of how the UK can prosper under ‘Brexit’, by remaining a member of the EMA, but accepting the decisions without political oversight (as currently happens with the European Commission). Additional freedom could be given to a UK regulator to accept decisions (where appropriate) from other agencies such as the Food & Drug Administration—further speeding access and making the UK a more attractive market. Such an arrangement would put the UK in a better position than the good position it is in currently. This would give patients (both now and in the future) the best access to treatment possible, and promote/attract an industry which employs (directly and indirectly) 500,000 jobs. PMID:28717397

  13. Experiences in certification of packages for transportation of fresh nuclear fuel in the context of new safety requirements established by IAEA regulations (IAEA-96 regulations, ST-1) for air transportation of nuclear materials (requirements to C-type packages)

    Energy Technology Data Exchange (ETDEWEB)

    Dudai, V.I.; Kovtun, A.D.; Matveev, V.Z.; Morenko, A.I.; Nilulin, V.M.; Shapovalov, V.I.; Yakushev, V.A.; Bobrovsky, V.S.; Rozhkov, V.V.; Agapov, A.M.; Kolesnikov, A.S. [Russian Federal Nuclear Centre - All-Russian Research Inst. of Experimental Physics, Sarov (Russian Federation)]|[JSC ' ' MSZ' ' , Electrostal (Russian Federation)]|[JSC ' ' NPCC' ' , Novosibirsk (Russian Federation)]|[Minatom of Russia, Moscow (Russian Federation)]|[Gosatomnadzor of Russia, Moscow (Russian Federation)

    2004-07-01

    Every year in Russia, a large amount of domestic and international transportation of fresh nuclear fuel (FNF) used in Russian and foreign energy and research atomic reactors and referred to fissile materials based on IAEA Regulations is performed. Here, bulk transportation is performed by air, and it concerns international transportation in particular. According to national ''Main Regulations for Safe Transport and physical Protection of Nuclear Materials (OPBZ- 83)'' and ''Regulations for the Safe Transport of Radioactive Materials'' of the International Atomic Energy Agency (IAEA Regulations), nuclear and radiation security under normal (accident free) and accident conditions of transport must be completely provided by the package design. In this context, high requirements to fissile packages exposed to heat and mechanical loads in transport accidents are imposed. A long-standing experience in accident free transportation of FM has shown that such approach to provide nuclear and radiation security pays for itself completely. Nevertheless, once in 10 years the International Atomic Energy Agency on every revision of the ''Regulations for the Safe Transport of Radioactive Materials'' places more stringent requirements upon the FM and transportation thereof, resulting from the objectively increasing risk associated with constant rise in volume and density of transportation, and also strained social and economical situation in a number of regions in the world. In the new edition of the IAEA Regulations (ST-1), published in 1996 and brought into force in 2001 (IAEA-96 Regulations), the requirements to FM packages conveyed by aircraft were radically changed. These requirements are completely presented in new Russian ''Regulations for the Safe Transport of Radioactive Materials'' (PBTRM- 2004) which will be brought into force in the time ahead.

  14. Calcium-calmodulin kinase I cooperatively regulates nucleocytoplasmic shuttling of CCTα by accessing a nuclear export signal.

    Science.gov (United States)

    Agassandian, Marianna; Chen, Bill B; Pulijala, Roopa; Kaercher, Leah; Glasser, Jennifer R; Mallampalli, Rama K

    2012-07-01

    We identified a new calmodulin kinase I (CaMKI) substrate, cytidyltransferase (CCTα), a crucial enzyme required for maintenance of cell membranes. CCTα becomes activated with translocation from the cytoplasm to the nuclear membrane, resulting in increased membrane phospholipids. Calcium-activated CCTα nuclear import is mediated by binding of its C-terminus to 14-3-3 ζ, a regulator of nuclear trafficking. Here CaMK1 phosphorylates residues within this C-terminus that signals association of CCTα with 14-3-3 ζ to initiate calcium-induced nuclear entry. CaMKI docks within the CCTα membrane-binding domain (residues 290-299), a sequence that displays similarities to a canonical nuclear export signal (NES) that also binds CRM1/exportin 1. Expression of a CFP-CCTα mutant lacking residues 290-299 in cells results in cytosolically retained enzyme. CRM1/exportin 1 was required for CCTα nuclear export, and its overexpression in cells was partially sufficient to trigger CCTα nuclear export despite calcium stimulation. An isolated CFP-290-299 peptide remained in the nucleus in the presence of leptomycin B but was able to target to the cytoplasm with farnesol. Thus CaMKI vies with CRM1/exportin 1 for access to a NES, and assembly of a CaMKI-14-3-3 ζ-CCTα complex is a key effector mechanism that drives nuclear CCTα translocation.

  15. Zinc fingers 1, 2, 5 and 6 of transcriptional regulator, PRDM4, are required for its nuclear localisation

    Energy Technology Data Exchange (ETDEWEB)

    Tunbak, Hale, E-mail: h.tunbak@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Georgiou, Christiana, E-mail: christiana.georgiou.10@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Guan, Cui, E-mail: c.guan@qmul.ac.uk [School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Richardson, William David, E-mail: w.richardson@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Chittka, Alexandra, E-mail: a.chittka@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-05-27

    PRDM4 is a member of the PRDM family of transcriptional regulators which control various aspects of cellular differentiation and proliferation. PRDM proteins exert their biological functions both in the cytosol and the nucleus of cells. All PRDM proteins are characterised by the presence of two distinct structural motifs, the PR/SET domain and the zinc finger (ZF) motifs. We previously observed that deletion of all six zinc fingers found in PRDM4 leads to its accumulation in the cytosol, whereas overexpressed full length PRDM4 is found predominantly in the nucleus. Here, we investigated the requirements for single zinc fingers in the nuclear localisation of PRDM4. We demonstrate that ZF's 1, 2, 5 and 6 contribute to the accumulation of PRDM4 in the nucleus. Their effect is additive as deleting either ZF1-2 or ZF 5–6 redistributes PRDM4 protein from being almost exclusively nuclear to cytosolic and nuclear. We investigated the potential mechanism of nuclear shuttling of PRDM4 via the importin α/β-mediated pathway and find that PRDM4 nuclear targeting is independent of α/β-mediated nuclear import. -- Highlights: •Zinc fingers 1, 2, 5, and 6 are necessary for efficient nuclear localisation of PRDM4. •Zinc fingers 3 and 4 are dispensable for nuclear localisation of PRDM4. •Zinc knuckle is dispensable for nuclear localisation of PRDM4. •PRDM4 nuclear transport is independent of importin α/β-mediated pathway of nuclear import.

  16. Regulation of medicinal plants for public health--European community monographs on herbal substances.

    Science.gov (United States)

    Knöss, Werner; Chinou, Ioanna

    2012-08-01

    The European legislation on medicinal products also addresses the medicinal use of products originating from plants. The objective of the legislation is to ensure the future existence of such products and to consider particular characteristics when assessing quality, efficacy, and safety. Two categories are defined: i) herbal medicinal products can be granted a marketing authorisation; and ii) traditional herbal medicinal products can be granted a registration based on their longstanding use if they are complying with a set of provisions ensuring their safe use. The Committee on Herbal Medicinal Products (HMPC) was established at the European Medicines Agency (EMA) to provide monographs and list entries on herbal substances and preparations thereof. Meanwhile, approx. 100 monographs have been published, which define a current scientific and regulatory standard for efficacy and safety of herbal substances and herbal preparations used in medicinal products. This harmonised European standard will facilitate the availability and adequate use of traditional herbal medicinal products and herbal medicinal products within the European Union. Consequent labelling shall also enable patients and health care professionals to differentiate medicinal products from other product categories like cosmetics, food supplements, and medical devices. Georg Thieme Verlag KG Stuttgart · New York.

  17. Fundamental rights and the European regulation of iConsumer contracts

    NARCIS (Netherlands)

    Mak, C.

    2008-01-01

    This paper addresses the question of how fundamental rights affect European legislation and adjudication on contracts regarding digital information services (iConsumer contracts). Fundamental rights may be seen as representing political choices for the protection of certain values in society, but at

  18. Media literacy: no longer the shrinking violet of European audiovisual media regulation?

    NARCIS (Netherlands)

    McGonagle, T.; Nikoltchev, S.

    2011-01-01

    The lead article in this IRIS plus provides a critical analysis of how the European audiovisual regulatory and policy framework seeks to promote media literacy. It examines pertinent definitional issues and explores the main rationales for the promotion of media literacy as a regulatory and policy

  19. Varieties of European Economic Law and Regulation : Liber Amicorum for Hans Micklitz

    NARCIS (Netherlands)

    Purnhagen, K.; Rott, P.

    2014-01-01

    This is the first book to comprehensively analyze the work of Hans Micklitz, one of the leading scholars in the field of EU economic law. It brings together analysts, academic friends and critics of Hans Micklitz and results in a unique collection of essays that evaluate his work on European

  20. Nickel allergy following European Union regulation in Denmark, Germany, Italy and the U.K

    DEFF Research Database (Denmark)

    Garg, S; Thyssen, J P; Uter, W

    2013-01-01

    Nickel allergy is common worldwide. It is associated with hand dermatitis, and sensitization is often induced by nickel-releasing jewellery. The European Union (EU) introduced legislation to control nickel content and release from jewellery and other consumer items through the EU Nickel Directive...

  1. A review of the organization, regulation, and financing practices of postgraduate education in clinical nursing in 12 European countries.

    Science.gov (United States)

    Rautiainen, Elina; Vallimies-Patomäki, Marjukka

    2016-01-01

    The aim of this study was to generate information of postgraduate education in clinical nursing in the EU member states. Data were collected via a structured electronic questionnaire and the questionnaire was sent to the government chief nurses in 26 EU countries in May 2013. Response rate was 46% (n=12). In total, 42 domains of specialization were identified. The most common domains were intensive care, mental health, operating room, emergency care, and pediatrics. Specialization programs were organized by university in two of the respondent countries, as residency program in one country, and as a mix of them in four countries. Regulation practices varied remarkably between the countries: scope of practice, subjects, entry requirements, length of education, description of the minimum competence requirements, and education standards related to the specialization programs were most often regulated by act, decree or other regulation. In some of the countries, no registration was required beyond the initial registration, whereas in some others, registration practices varied depending on the specialization program. New information was gathered on the regulation practices of postgraduate education in clinical nursing in the European Region concerning title provision, entry requirements, and financing practices. The awarded title on specialization programs depended on the level of postgraduate education, and the title might vary between the domains. General clinical experience was included in the entry requirements in seven countries. The government was mainly responsible for financing the postgraduate education in four countries, employer in three countries, and in the rest of the countries, there was a combination of different financiers. The importance of knowledge exchange on postgraduate education across the European countries needs to be acknowledged. Information provided by this study on international regulation practices provides useful information for the policy

  2. The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans.

    Science.gov (United States)

    Liang, Bin; Ferguson, Kim; Kadyk, Lisa; Watts, Jennifer L

    2010-03-25

    Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and sterol regulatory element binding protein (SREBP) sbp-1 mutants. Furthermore, inactivation of nhr-64 improves the growth rate of the fat-6;fat-7and sbp-1 strains. While nhr-64RNAi subtly affects fatty acid composition and fat storage in wild-type C. elegans, its effects on lipid metabolism are most apparent in the background of stearoyl-CoA desaturase or SREBP deficiency. NHR-64 displays transcriptional activating activity when expressed in yeast, and inactivation of nhr-64 affects the expression of at least 14 metabolic genes. Wild-type worms treated with nhr-64 RNAi display increased expression of acetyl-CoA carboxylase as well as increased abundance of de novo synthesized monomethyl branched chain fatty acids, suggesting an increase in fat synthesis. However, reduced expression of the acetyl-CoA synthetase gene acs-2 and an acyl-CoA oxidase gene indicates that a key role of NHR-64 may be to promote fatty acid oxidation in mitochondria and peroxisomes. These studies reveal that NHR-64 is an important regulator of fat storage in C. elegans.

  3. Nuclear receptors and epigenetic signaling: novel regulators of glycogen metabolism in skeletal muscle.

    Science.gov (United States)

    Wang, Shu-Ching Mary; Muscat, George E O

    2013-08-01

    Glycogen is an energy storage depot for the mammalian species. This review focuses on recent developments that have identified the role of nuclear hormone receptor (NR) signaling and epigenomic control in the regulation of important genes that modulate glycogen metabolism. Specifically, new studies have revealed that the NR4A subgroup (of the NR superfamily) are strikingly sensitive to beta-adrenergic stimulation in skeletal muscle, and transgenic studies in mice have revealed the expression of these NRs affects endurance and glycogen levels in muscle. Furthermore, other studies have demonstrated that one of the NR coregulator class of enzymes that mediate chromatin remodeling, the histone methyltransferases (for example, protein arginine methyltransferase 4) regulates the expression of several genes involved in glycogen metabolism and glycogen storage diseases in skeletal muscle. Importantly, NRs and histone methyltransferases, have the potential to be pharmacologically exploited and may provide novel targets in the quest to treat disorders of glycogen storage. © 2013 International Union of Biochemistry and Molecular Biology.

  4. The Substitution Principle within the REACH Regulation: Nuclear Receptor-Bound Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Stefano Lorenzetti

    2017-09-01

    Full Text Available Within the REACH Regulation (EC/1907/2006, the substitution principle for chemicals classified as Substances of Very High Concern (SVHC for either human health or environmental risks has been implemented in order to support their replacement by suitable alternatives. Considering the thousands of chemicals to be tested within the frame of REACH, animal testing by internationally-accepted guidelines sounds unreasonable in terms of the required time, costs as well ethical issues. Hence, REACH recommended also the use of alternative methods to animal experimentation although no validated in silico or in vitro tools were available when regulation entried into force. To search for suitable alternatives to SVHC having an Endocrine Disruptor (ED-like Mode-of-Action (MoA by means of an integrated, tiered in silico-in vitro approach, the EU-granted project LIFE-EDESIA (contract no. LIFE12 ENV/IT/000633 is combining computational-based tools and cell-based bioassays, in order to develop a no-animal testing procedure to screen for chemicals having less or no toxicity in terms of endocrine disruption-like activities. A general view of the no-animal testing approach implementing REACH and the substitution principle will be given, emphasising ligand-nuclear receptor (NR assessment by molecular docking (one of the LIFE-EDESIA in silico approaches and the use of clinical biomarkers in in vitro toxicology to detect ED-like adverse effects in cell-based bioassays.

  5. Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells.

    Science.gov (United States)

    Shaheen, Fozia; Grammatopoulos, Dimitris K; Müller, Jürgen; Zammit, Victor A; Lehnert, Hendrik

    2014-09-01

    Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex. By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan. Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration. Accelerated telomere shortening in both human and animal models has been documented in conditions associated with insulin resistance, including T2DM. We investigated the role of TERT, in regulating cellular glucose utilisation by using the myoblastoma cell line C2C12, as well as primary mouse and human skeletal muscle cells. Inhibition of TERT expression or activity by using siRNA (100nM) or specific inhibitors (100nM) reduced basal 2-deoxyglucose uptake by ~50%, in all cell types, without altering insulin responsiveness. In contrast, TERT over-expression increased glucose uptake by 3.25-fold. In C2C12 cells TERT protein was mostly localised intracellularly and stimulation of cells with insulin induced translocation to the plasma membrane. Furthermore, co-immunoprecipitation experiments in C2C12 cells showed that TERT was constitutively associated with glucose transporters (GLUTs) 1, 4 and 12 via an insulin insensitive interaction that also did not require intact PI3-K and mTOR pathways. Collectively, these findings identified a novel extra-nuclear function of TERT that regulates an insulin-insensitive pathway involved in glucose uptake in human and mouse skeletal muscle cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression.

    Science.gov (United States)

    Grund, Stefanie E; Fischer, Tamás; Cabal, Ghislain G; Antúnez, Oreto; Pérez-Ortín, José E; Hurt, Ed

    2008-09-08

    Inner nuclear membrane proteins containing a LEM (LAP2, emerin, and MAN1) domain participate in different processes, including chromatin organization, gene expression, and nuclear envelope biogenesis. In this study, we identify a robust genetic interaction between transcription export (TREX) factors and yeast Src1, an integral inner nuclear membrane protein that is homologous to vertebrate LEM2. DNA macroarray analysis revealed that the expression of the phosphate-regulated genes PHO11, PHO12, and PHO84 is up-regulated in src1Delta cells. Notably, these PHO genes are located in subtelomeric regions of chromatin and exhibit a perinuclear location in vivo. Src1 spans the nuclear membrane twice and exposes its N and C domains with putative DNA-binding motifs to the nucleoplasm. Genome-wide chromatin immunoprecipitation-on-chip analyses indicated that Src1 is highly enriched at telomeres and subtelomeric regions of the yeast chromosomes. Our data show that the inner nuclear membrane protein Src1 functions at the interface between subtelomeric gene expression and TREX-dependent messenger RNA export through the nuclear pore complexes.

  7. A mechanism for negative gene regulation in Autographa californica multinucleocapsid nuclear polyhedrosis virus

    Science.gov (United States)

    Leisy, D.J.; Rasmussen, C.; Owusu, E.O.; Rohrmann, G.F.

    1997-01-01

    The Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) ie-1 gene product (IE-1) is thought to play a central role in stimulating early viral transcription. IE-1 has been demonstrated to activate several early viral gene promoters and to negatively regulate the promoters of two other AcMNPV regulatory genes, ie-0 and ie-2. Our results indicate that IE-1 negatively regulates the expression of certain genes by binding directly, or as part of a complex, to promoter regions containing a specific IE-1-binding motif (5'-ACBYGTAA-3') near their mRNA start sites. The IE-1 binding motif was also found within the palindromic sequences of AcMNPV homologous repeat (hr) regions that have been shown to bind IE-1. The role of this IE-1 binding motif in the regulation of the ie-2 and pe-38 promoters was examined by introducing mutations in these promoters in which the central 6 bp were replaced with Bg/II sites. GUS reporter constructs containing ie-2 and pe-38 promoter fragments with and without these specific mutations were cotransfected into Sf9 cells with various amounts of an ie-1-containing plasmid (ple-1). Comparisons of GUS expression produced by the mutant and wild-type constructs demonstrated that the IE-1 binding motif mediated a significant decrease in expression from the ie-2 and pe-38 promoters in response to increasing pIe-1 concentrations. Electrophoretic mobility shift assays with pIe-1-transfected cell extracts and supershift assays with IE-1- specific antiserum demonstrated that IE-1 binds to promoter fragments containing the IE-1 binding motif but does not bind to promoter fragments lacking this motif.

  8. U.S. Nuclear Regulatory Commission seismic regulations, research, and emerging trends

    Energy Technology Data Exchange (ETDEWEB)

    Chokshi, N.C.; Shao, L.C. [Nuclear Regulatory Commission, Washington, DC (United States). Office of Nuclear Regulatory Research; Apostolakis, G.

    1997-03-01

    Historically in the United States, seismic issues have played an important role in determining site suitability and, in some cases, have determined the ultimate fate of power plants. During the late 1960s and early 1970s, a seismic design philosophy evolved as the licensing of the earlier plants was in progress. Concepts such as the Safe Shutdown Earthquake (SSE) and the Operating Basis Earthquake (OBE) emerged and were codified into the federal regulations with the publication in December 1973 of Appendix A, `Seismic and Geologic Siting Criteria for Nuclear Power Plants,` to 10 CFR Part 100, `Reactor Site Criteria.` Seismic considerations are also important in siting and design of other fuel cycle and waste facilities. In this paper, a brief overview of the current seismic siting and design regulations are described along with some recent and planned changes based on the past experience, advancement in the state-of-the-art, and research results. In particular, the recently revised siting rule and use of the probabilistic seismic hazard analysis in implementation of the rule will be described in more detail. The paper includes discussion of some recent seismic issues and research activities, including issues related to aging. Some emerging trends are highlighted. In particular, the paper focuses on use of `expert opinion` in the probabilistic analysis and risk informed regulations and their implications to the seismic design. An additional focus is on international cooperative programs and how to initiate such programs such that better use can be made of limited resources to resolve issues of common interest. (author)

  9. French Jardé's law and European regulation on drug trials: Harmonization and implementation of new rules.

    Science.gov (United States)

    Deplanque, Dominique; Sénéchal-Cohen, Sophie; Lemaire, François

    2017-02-01

    Jardé's law, concerning research studies in humans, was enacted in March 2012 but did not come into force until November 2016. This delay is largely explained by the adoption of a European regulation on clinical trials on medicinal products that will probably not be applicable until October 2018. In addition to covering the respective areas of the French and European legislation, the round table provided an opportunity to discuss the principal measures that will apply to future research, particularly those concerning the operational procedures of the ethics committees and the national committee for research in humans, as well as measures relating to the management of serious adverse effects, more specifically in phase I studies in subjects not presenting with any disorder. This round table also enabled the formulation of recommendations to better anticipate the practical difficulties that the regulatory changes might engender. Finally, we highlight the numerous challenges in terms of training that these important regulatory changes impose and the absolute necessity to best adapt the restrictions to those that are planned in numerous other European countries so that France remains competitive in terms of clinical research and so that French patients may continue to benefit rapidly from the most innovative treatments. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. Legal analysis of systemic investment protection regulation in the European Union’s financial sector

    Directory of Open Access Journals (Sweden)

    Bocs L.

    2018-01-01

    Full Text Available After the Treaty of Lisbon the European Union has an exclusive and uniform competence regarding investment agreements within its common commercial policy. Yet the political events in 2016 showed that there are still many regional differences politically and economically, especially after the so-called Brexit and negotiations with the United States of America in relation to transatlantic trade and investment. Therefore, the aim of the research is to determine the legal framework and related problems for unified investment protection within the European Union. Using descriptive, logical and deductive methodology the paper establishes a juristic base consensus for trade and investment policies, concludes that so far those policies have been systemically neglected due to regional differences in economic development and accordingly suggests to unify and protect the common investment policies by using already existing regional judicial mechanisms of member states within a unified code of conduct.

  11. NEW PROPOSAL FOR EUROPEAN UNION REGULATIONS ON MEDICAL DEVICES AND IN VITRO DIAGNOSTIC MEDICAL DEVICES

    OpenAIRE

    Mariela Yaneva-Deliverska

    2012-01-01

    Appropriate legislation is fundamental to ensuring the highest level of health protection and effective innovation. Until the 1990s, each European Union country had its own approach to device evaluation but governments needed to put in place policies that will address all elements related to medical devices, ranging from access to high quality, affordable products, through to their safe and appropriate use and disposal. In order to ensure that patients, consumers and healthcare professionals ...

  12. Phenobarbital Regulates Nuclear Expression of HNF-4α in Mouse and Rat Hepatocytes Independent of CAR and PXR

    Science.gov (United States)

    Bell, Aaron W.; Michalopoulos, George K.

    2007-01-01

    Phenobarbital is a lipophilic molecule used as a sedative and antiepileptic drug that elicits a multitude of effects in the liver, including gross liver enlargement, hepatocyte hypertrophy, and induced expression of drug-metabolizing enzymes and other liver-specific genes. The constitutive androstane receptor (CAR; NR1I3) and to a lesser extent the pregnane X receptor (PXR; NR1I2) are responsible for mediating induction of many phenobarbital-responsive genes. However, CAR-mediated transcriptional control of some genes is critically dependent on hepatocyte nuclear factor 4 alpha (HNF-4α; NR2A1), which itself regulates multiple liver-specific genes involved in hepatic growth, metabolism, and differentiation. We studied the effects of phenobarbital on HNF-4α expression in hepatocytes and provide evidence that HNF-4α nuclear expression is regulated in response to phenobarbital. Real-time polymerase chain reaction analyses revealed that HNF-4α mRNA is modestly up-regulated by phenobarbital. In addition, nuclear expression of HNF-4α protein is significantly elevated 3 hours after the administration of phenobarbital in wild-type, CAR−/−, and CAR−/−/PXR−/− mice. In vitro analysis revealed that phenobarbital-induced HNF-4α expression is both time- and dose dependent. In addition, the phosphatase inhibitor okadaic acid and the Ca2−/calmodulin-dependent protein kinase II inhibitor KN62 block nuclear induction of HNF-4α by phenobarbital. Furthermore, HNF-4α nuclear expression is enhanced by inhibition of cyclic AMP– dependent protein kinase A. In conclusion, induced nuclear expression of HNF-4α and CAR is an integral part of the phenobarbital response, aimed at coordinated regulation of genes involved in drug metabolism and detoxification as well as maintenance of liver function. PMID:16799975

  13. Financial Regulations and the Diversification of Funding Sources in Higher Education Institutions: Selected European Experiences

    Science.gov (United States)

    Stachowiak-Kudla, Monika; Kudla, Janusz

    2017-01-01

    The paper addresses the problem of the financial regulations' impact on the share of private financing in higher education institutions (HEIs). The authors postulate the trade-off between the size and stability of public financing and the regulations fostering stability of HEIs' funds. If the public sources are insufficient then the regulations…

  14. Corporate coalitions and policy making in the European Union: how and why British American Tobacco promoted "Better Regulation".

    Science.gov (United States)

    Smith, Katherine Elizabeth; Fooks, Gary; Gilmore, Anna B; Collin, Jeff; Weishaar, Heide

    2015-04-01

    Over the past fifteen years, an interconnected set of regulatory reforms, known as Better Regulation, has been adopted across Europe, marking a significant shift in the way that European Union policies are developed. There has been little exploration of the origins of these reforms, which include mandatory ex ante impact assessment. Drawing on documentary and interview data, this article discusses how and why large corporations, notably British American Tobacco (BAT), worked to influence and promote these reforms. Our analysis highlights (1) how policy entrepreneurs with sufficient resources (such as large corporations) can shape the membership and direction of advocacy coalitions; (2) the extent to which "think tanks" may be prepared to lobby on behalf of commercial clients; and (3) why regulated industries (including tobacco) may favor the use of "evidence tools," such as impact assessments, in policy making. We argue that a key aspect of BAT's ability to shape regulatory reform involved the deliberate construction of a vaguely defined idea that could be strategically adapted to appeal to diverse constituencies. We discuss the theoretical implications of this finding for the Advocacy Coalition Framework, as well as the practical implications of the findings for efforts to promote transparency and public health in the European Union. Copyright © 2015 by Duke University Press.

  15. Food safety regulations: what we learned from the Fukushima nuclear accident.

    Science.gov (United States)

    Hamada, Nobuyuki; Ogino, Haruyuki

    2012-09-01

    On 11 March 2011, the magnitude-9.0 earthquake and a substantial tsunami struck off the northeast coast of Japan. The Fukushima nuclear power plants were inundated and stricken, followed by radionuclide releases outside the crippled reactors. Provisional regulation values for radioactivity in food and drink were set on 17 March and were adopted from the preset index values, except that for radioiodines in water and milk ingested by infants. For radiocesiums, uranium, plutonium and transuranic α emitters, index values were defined in all food and drink not to exceed a committed effective dose of 5 mSv/year. Index values for radioiodines were defined not to exceed a committed equivalent dose to the thyroid of 50 mSv/year, and set in water, milk and some vegetables, but not in other foodstuffs. Index values were calculated as radioactive concentrations of indicator radionuclides ((131)I for radioiodines, (134)Cs and (137)Cs for radiocesiums) by postulating the relative radioactive concentration of coexisting radionuclides (e.g., (132)I, (133)I, (134)I, (135)I and (132)Te for (131)I). Surveys were thence conducted to monitor levels of (131)I, (134)Cs and (137)Cs. Provisional regulation values were exceeded in tap water, raw milk and some vegetables, and restrictions on distribution and consumption began on 21 March. Fish contaminated with radioiodines at levels of concern were then detected, so that the provisional regulation value for radioiodines in seafood adopted from that in vegetables were additionally set on 5 April. Overall, restrictions started within 25 days after the first excess in each food or drink item, and maximum levels were detected in leafy vegetables (54,100 Bq/kg for (131)I, and a total of 82,000 Bq/kg for (134)Cs and (137)Cs). This paper focuses on the logic behind such food safety regulations, and discusses its underlying issues. The outlines of the food monitoring results for 24,685 samples and the enforced restrictions will also be described

  16. Is there health inequity in Europe today? The ‘strange case’ of the application of an European regulation to cartilage repair

    Directory of Open Access Journals (Sweden)

    Roberto Beretta

    2016-03-01

    Full Text Available An important regulation, issued by the European Community in 2008, regulates the authorisation and supervision of advanced therapy medicinal products (ATMP and subsequent follow up in Europe. This law contains a Hospital Exemption clause, under which some hospitals in some countries can be exempted from the regulations governing ATMPs. The application of this regulation in Europe has resulted in differences in the costs of cell therapy for cartilage injuries in Germany compared with the costs in other European countries and in the U.S. The present paper argues on the real impact of political decisions on the health of citizens, on economy of healthcare systems, and highlights a possible case of inequality among European citizens with respect to cartilage repair procedures.

  17. Association between stricter alcohol advertising regulations and lower hazardous drinking across European countries.

    Science.gov (United States)

    Bosque-Prous, Marina; Espelt, Albert; Guitart, Anna M; Bartroli, Montserrat; Villalbí, Joan R; Brugal, M Teresa

    2014-10-01

    To analyse the association between alcohol advertising restrictions and the prevalence of hazardous drinking among people aged 50-64 years in 16 European countries, taking into account both individual and contextual-level factors (alcohol taxation, availability, etc.). Cross-sectional study based on SHARE project surveys. A total of 27 773 subjects, aged 50-64 years, from 16 European countries who participated in wave 4 of the SHARE (Survey of Health, Ageing and Retirement in Europe) project. We estimated the prevalence of hazardous drinking (through adaptation of the SHARE questions to the scheme used by the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) for each country. To determine whether the degree of advertising restrictions was associated with prevalence of hazardous drinking, we fitted robust variance multi-level Poisson models, adjusting for various individual and contextual variables. Prevalence ratios (PR) and their 95% confidence intervals (95% CI) were obtained. The observed prevalence of hazardous drinking was 24.1%, varying by sex and country. Countries with greater advertising restrictions had lower prevalence of hazardous drinking: 30.6% (95% CI = 29.3-31.8) in countries with no restrictions, 20.3% (95% CI = 19.3-21.2) in countries with some restrictions and 14.4% (95% CI = 11.9-16.8) in those with greatest restrictions. The PR found (with respect to countries with greatest restrictions) were 1.36 (95% CI = 0.90-2.06) for countries with some restrictions and 1.95 (95% CI = 1.31-2.91) for those with no advertising restrictions. The extent of advertising restrictions in European countries is associated inversely with prevalence of hazardous drinking in people aged 50-64 years. © 2014 Society for the Study of Addiction.

  18. Regulating mobile advertising in the European Union and the United States

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2008-01-01

    Mobile advertising is a gradually developing component of the marketing mix that includes advertisements directed to or accessed on consumers' mobile devices. Growing concerns about the protection of the consumers' personal data are being raised since mobile advertising may become an extremely...... intrusive practice in an intimate personal space. Approaches of protecting the consumers' personal information differ greatly throughout the world. This article contrasts the regulatory environment in the European Union and in the United States applicable to the consumer's privacy and personal data used...... for mobile advertising purposes while also examining the effectiveness of each of these approaches....

  19. Nuclear factor E2-related factor-2 (Nrf2) expression and regulation in male reproductive tract.

    Science.gov (United States)

    Wajda, Anna; Łapczuk, Joanna; Grabowska, Marta; Słojewski, Marcin; Laszczyńska, Maria; Urasińska, Elżbieta; Droździk, Marek

    2016-02-01

    Nuclear factor E2-related factor-2 (Nrf2, Nfe2l2) plays an important, protective role in many tissues. However, information on molecular mechanisms of detoxification and drug metabolism regulated by Nrf2/NRF2 in testis and epididymis is scarce, but it may help to better characterize the function of blood-testis and epididymis barriers. Constitutive gene expression was analyzed by real time PCR with TaqMan Assay using ΔCT-method. Additionally, gene expression after treatment with oltipraz- specific Nrf2 inducer was evaluated using ΔΔCT-method. Cellular localization of the Nrf2 was visualized by immunohistochemical reaction. The study showed that Nrf2 mRNA level in rat epididymis was higher than in testis. In human tissues, both testis and epididymis demonstrated similar expression levels of NRF2. Immunohistochemical analysis revealed NRF2/Nrf2 protein expression in testis and epididymis, which in the case of testis was dependant on spermatogenesis stage. Both in human and rat tissues constitutive expression of NQO1/Nqo1 was slightly higher in epididymis than in testis. Other Nrf2 regulated genes: GCLC/Gclc and UGT1A6/Ugt1a6 showed different ratios of testis/epididymis/liver expression levels. Treatment with oltipraz (Nrf2 inducer) resulted in significant induction of Nrf2 expression solely in corpus of epididymis. Components of the Nrf2/NRF2 system along with coordinated genes are expressed in testis and epididymis. Moreover, some interspecies differences between rat and human were observed, which may impact extrapolation of experimental data into clinical findings. Studies on animal model showed that corpus of epididymis is the most responsive part of the male reproductive tract to oltipraz exposure at the gene expression level. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Managing scientific, technical and regulatory innovation in regulated bioanalysis: a discussion paper from the European Bioanalysis Forum.

    Science.gov (United States)

    Timmerman, Philip; Henderson, Neil; Smeraglia, John; Mulder, Hans; Ingelse, Benno; Brudny-Kloeppel, Margarete; Companjen, Arjen

    2013-01-01

    On 12-13 June 2012, the European Bioanalysis Forum hosted its third Focus Meeting in Brussels (Belgium). At the meeting, a panel discussion was held on the hurdles that the bioanalytical community encounters when adopting new technologies or managing regulated bioanalysis expectations around emerging technologies. Over the last few years, the industry has seen many new technologies maturing. As they became available, the bioanalytical scientist has observed that implementing these technologies in the regulated environment has become increasingly challenging. For one, scientific developments and regulatory expectations may not go hand in hand. At the same time, the pharmaceutical industry has become increasingly risk averse in their response to these real or perceived higher expectations in regulated bioanalysis. As a downstream consequence, the potential result of overinterpretation of guidance or occasional widespread and premature implementation of responses to health authority inspections, industry may be contributing significantly to raising the bar on some processes related to day-to-day practices in the bioanalytical laboratory. Last but not least, with the community being satisfied with the performance of the current tools, potential complacency can be observed in the regulated bioanalytical community because existing technologies, such as LC-MS/MS and ligand-binding assays, have served and still are serving them extremely well. Hence, the question 'what's next after LC-MS/MS or ELISA?' is not resonating with many scientists as pertinently compared with 'What's next after RIA, GC or LC-UV?', which was the key question in the 1990s, certainly in the context of an increasing effort needed to validate these new tools. With this article, the European Bioanalysis Forum aims to stimulate an open dialogue between all stakeholders in regulated bioanalysis to positively influence how we balance science, process and regulations in day-to-day work. This discussion

  1. Sigma-1 Receptors Regulate Bcl-2 Expression by Reactive Oxygen Species-Dependent Transcriptional Regulation of Nuclear Factor κB

    Science.gov (United States)

    Meunier, Johann

    2010-01-01

    The expression of Bcl-2, the major antiapoptotic member of the Bcl-2 family, is under complex controls of several factors, including reactive oxygen species (ROS). The σ-1 receptor (Sig-1R), which was recently identified as a novel molecular chaperone at the mitochondria-associated endoplasmic reticulum membrane (MAM), has been shown to exert robust cellular protective actions. However, mechanisms underlying the antiapoptotic action of the Sig-1R remain to be clarified. Here, we found that the Sig-1R promotes cellular survival by regulating the Bcl-2 expression in Chinese hamster ovary cells. Although both Sig-1Rs and Bcl-2 are highly enriched at the MAM, Sig-1Rs neither associate physically with Bcl-2 nor regulate stability of Bcl-2 proteins. However, Sig-1Rs tonically regulate the expression of Bcl-2 proteins. Knockdown of Sig-1Rs down-regulates whereas overexpression of Sig-1Rs up-regulates bcl-2 mRNA, indicating that the Sig-1R transcriptionally regulates the expression of Bcl-2. The effect of Sig-1R small interfering RNA down-regulating Bcl-2 was blocked by ROS scavengers and by the inhibitor of the ROS-inducible transcription factor nuclear factor κB (NF-κB). Knockdown of Sig-1Rs up-regulates p105, the precursor of NF-κB, while concomitantly decreasing inhibitor of nuclear factor-κBα. Sig-1R knockdown also accelerates the conversion of p105 to the active form p50. Lastly, we showed that knockdown of Sig-1Rs potentiates H2O2-induced apoptosis; the action is blocked by either the NF-κB inhibitor oridonin or overexpression of Bcl-2. Thus, these findings suggest that Sig-1Rs promote cell survival, at least in part, by transcriptionally regulating Bcl-2 expression via the ROS/NF-κB pathway. PMID:19855099

  2. Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon.

    Science.gov (United States)

    Vielhaber, E; Eide, E; Rivers, A; Gao, Z H; Virshup, D M

    2000-07-01

    The molecular oscillator that keeps circadian time is generated by a negative feedback loop. Nuclear entry of circadian regulatory proteins that inhibit transcription from E-box-containing promoters appears to be a critical component of this loop in both Drosophila and mammals. The Drosophila double-time gene product, a casein kinase I epsilon (CKIepsilon) homolog, has been reported to interact with dPER and regulate circadian cycle length. We find that mammalian CKIepsilon binds to and phosphorylates the murine circadian regulator mPER1. Unlike both dPER and mPER2, mPER1 expressed alone in HEK 293 cells is predominantly a nuclear protein. Two distinct mechanisms appear to retard mPER1 nuclear entry. First, coexpression of mPER2 leads to mPER1-mPER2 heterodimer formation and cytoplasmic colocalization. Second, coexpression of CKIepsilon leads to masking of the mPER1 nuclear localization signal and phosphorylation-dependent cytoplasmic retention of both proteins. CKIepsilon may regulate mammalian circadian rhythm by controlling the rate at which mPER1 enters the nucleus.

  3. Nuclear receptors as regulators of stem cell and cancer stem cell metabolism.

    Science.gov (United States)

    Simandi, Zoltan; Cuaranta-Monroy, Ixchelt; Nagy, Laszlo

    2013-12-01

    Cellular metabolism is underpinning physiological processes in all cells. These include housekeeping functions as well as specific activities unique to a particular cell type. A growing number of studies in various experimental models indicate that metabolism is tightly connected to embryonic development as well. It is also emerging that metabolic processes have regulatory roles and by changing metabolism, cellular processes and even fates can be influenced. Nuclear receptors (NRs) are transcription factors, responding to changes in metabolites and are implicated in diverse biological processes such as embryonic development, differentiation, metabolism and cancer. Therefore, NRs are key links between metabolism and cell fate decisions. In this review, we introduce ESRRβ, DAX-1 and LRH-1 as putative regulators of metabolism in pluripotent embryonic stem cells. We also discuss the role of TR4, NGF1β, LXRβ and RARs in stemness. In addition, we summarize our current understanding of the potential roles of NRs in cancer stem cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Metrology for decommissioning nuclear facilities: Partial outcomes of joint research project within the European Metrology Research Program.

    Science.gov (United States)

    Suran, Jiri; Kovar, Petr; Smoldasova, Jana; Solc, Jaroslav; Van Ammel, Raf; Garcia Miranda, Maria; Russell, Ben; Arnold, Dirk; Zapata-García, Daniel; Boden, Sven; Rogiers, Bart; Sand, Johan; Peräjärvi, Kari; Holm, Philip; Hay, Bruno; Failleau, Guillaume; Plumeri, Stephane; Laurent Beck, Yves; Grisa, Tomas

    2017-09-01

    Decommissioning of nuclear facilities incurs high costs regarding the accurate characterisation and correct disposal of the decommissioned materials. Therefore, there is a need for the implementation of new and traceable measurement technologies to select the appropriate release or disposal route of radioactive wastes. This paper addresses some of the innovative outcomes of the project "Metrology for Decommissioning Nuclear Facilities" related to mapping of contamination inside nuclear facilities, waste clearance measurement, Raman distributed temperature sensing for long term repository integrity monitoring and validation of radiochemical procedures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. HuR-Regulated mRNAs Associated with Nuclear hnRNP A1-RNP Complexes

    Directory of Open Access Journals (Sweden)

    Apostolia Guialis

    2013-10-01

    Full Text Available Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of immunoselected hnRNP complexes and having a major nuclear localization. Specifically, we present here the application of the RNA-immunoprecipitation (RIP-Chip technology to identify a population of nuclear transcripts associated with hnRNP A1-RNPs as isolated from the nuclear extract of either HuR WT or HuR-depleted (KO mouse embryonic fibroblast (MEF cells. The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced with the nuclear hnRNP A1-RNP complexes. Real time PCR analysis was applied to validate a selected number of nuclear mRNA transcripts, as well as to identify pre-spliced transcripts (in addition to their mature mRNA counterpart within the isolated nuclear hnRNP A1-RNPs. The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle indicating their concerted function in mRNA metabolism.

  6. Impact of European pharmaceutical price regulation on generic price competition: a review.

    Science.gov (United States)

    Puig-Junoy, Jaume

    2010-01-01

    Although economic theory indicates that it should not be necessary to intervene in the generic drug market through price regulation, most EU countries intervene in this market, both by regulating the maximum sale price of generics (price cap) and by setting the maximum reimbursement rate, especially by means of reference pricing systems. We analyse current knowledge of the impact of direct price-cap regulation of generic drugs and the implementation of systems regulating the reimbursement rate, particularly through reference pricing and similar tools, on dynamic price competition between generic competitors in Europe. A literature search was carried out in the EconLit and PubMed databases, and on Google Scholar. The search included papers published in English or Spanish between January 2000 and July 2009. Inclusion criteria included that studies had to present empirical results of a quantitative nature for EU countries of the impact of price capping and/or regulation of the reimbursement rate (reference pricing or similar systems) on price dynamics, corresponding to pharmacy sales, in the generic drug market. The available evidence indicates that price-cap regulation leads to a levelling off of generic prices at a higher level than would occur in the absence of this regulation. Reference pricing systems cause an obvious and almost compulsory reduction in the consumer price of all pharmaceuticals subject to this system, to a varying degree in different countries and periods, the reduction being greater for originator-branded drugs than for generics. In several countries with a reference pricing system, it was observed that generics with a consumer price lower than the reference price do not undergo price reductions until the reference price is reduced, even when there are other lower-priced generics on the market (absence of price competition below the reference price). Beyond the price reduction forced by the price-cap and/or reference pricing regulation itself

  7. Speaker-Oriented Classroom Acoustics Design Guidelines in the Context of Current Regulations in European Countries

    DEFF Research Database (Denmark)

    Pelegrin Garcia, David; Brunskog, Jonas; Rasmussen, Birgit

    2014-01-01

    experienced at work. With the aim of improving working conditions for teachers, this article presents guidelines for classroom acoustics design that meet simultaneously criteria of vocal comfort and speech intelligibility, which may be of use in future discussions for updating regulatory requirements......Most European countries have regulatory requirements or guidelines for reverberation time in classrooms which have the goal of enhancing speech intelligibility and reducing noise levels in schools. At the same time, school teachers suffer frequently from voice problems due to high vocal load...... in classroom acoustics. Two room acoustic parameters are shown relevant for a speaker: the voice support, linked to vocal effort, and the decay time derived from an oral-binaural impulse response, linked to vocal comfort. Theoretical prediction models for room-averaged values of these parameters are combined...

  8. Nuclear reaction

    CERN Multimedia

    Penwarden, C

    2001-01-01

    At the European Research Organization for Nuclear Research, Nobel laureates delve into the mysteries of particle physics. But when they invited artists from across the continent to visit their site in Geneva, they wanted a new kind of experiment.

  9. How does medical device regulation perform in the United States and the European union? A systematic review.

    Science.gov (United States)

    Kramer, Daniel B; Xu, Shuai; Kesselheim, Aaron S

    2012-01-01

    Policymakers and regulators in the United States (US) and the European Union (EU) are weighing reforms to their medical device approval and post-market surveillance systems. Data may be available that identify strengths and weakness of the approaches to medical device regulation in these settings. We performed a systematic review to find empirical studies evaluating medical device regulation in the US or EU. We searched Medline using two nested categories that included medical devices and glossary terms attributable to the US Food and Drug Administration and the EU, following PRISMA guidelines for systematic reviews. We supplemented this search with a review of the US Government Accountability Office online database for reports on US Food and Drug Administration device regulation, consultations with local experts in the field, manual reference mining of selected articles, and Google searches using the same key terms used in the Medline search. We found studies of premarket evaluation and timing (n = 9), studies of device recalls (n = 8), and surveys of device manufacturers (n = 3). These studies provide evidence of quality problems in pre-market submissions in the US, provide conflicting views of device safety based largely on recall data, and relay perceptions of some industry leaders from self-surveys. Few studies have quantitatively assessed medical device regulation in either the US or EU. Existing studies of US and EU device approval and post-market evaluation performance suggest that policy reforms are necessary for both systems, including improving classification of devices in the US and promoting transparency and post-market oversight in the EU. Assessment of regulatory performance in both settings is limited by lack of data on post-approval safety outcomes. Changes to these device approval and post-marketing systems must be accompanied by ongoing research to ensure that there is better assessment of what works in either setting.

  10. How does medical device regulation perform in the United States and the European union? A systematic review.

    Directory of Open Access Journals (Sweden)

    Daniel B Kramer

    Full Text Available Policymakers and regulators in the United States (US and the European Union (EU are weighing reforms to their medical device approval and post-market surveillance systems. Data may be available that identify strengths and weakness of the approaches to medical device regulation in these settings.We performed a systematic review to find empirical studies evaluating medical device regulation in the US or EU. We searched Medline using two nested categories that included medical devices and glossary terms attributable to the US Food and Drug Administration and the EU, following PRISMA guidelines for systematic reviews. We supplemented this search with a review of the US Government Accountability Office online database for reports on US Food and Drug Administration device regulation, consultations with local experts in the field, manual reference mining of selected articles, and Google searches using the same key terms used in the Medline search. We found studies of premarket evaluation and timing (n = 9, studies of device recalls (n = 8, and surveys of device manufacturers (n = 3. These studies provide evidence of quality problems in pre-market submissions in the US, provide conflicting views of device safety based largely on recall data, and relay perceptions of some industry leaders from self-surveys.Few studies have quantitatively assessed medical device regulation in either the US or EU. Existing studies of US and EU device approval and post-market evaluation performance suggest that policy reforms are necessary for both systems, including improving classification of devices in the US and promoting transparency and post-market oversight in the EU. Assessment of regulatory performance in both settings is limited by lack of data on post-approval safety outcomes. Changes to these device approval and post-marketing systems must be accompanied by ongoing research to ensure that there is better assessment of what works in either setting.

  11. Regulations, policies and practices concerning work stress in five European countries

    NARCIS (Netherlands)

    Kompier, M.; Gier, E. de; Smulders, P.; Draaisma, D.

    1994-01-01

    A comparative inventory of regulations, policies and practices in The Netherlands, Sweden, UK, Germany and France with regard to the prevention of work stress was carried out. In each country data were collected by means of interviews with key informants and through exploring relevant documents and

  12. Different approaches of European regulations for fire design of steel structural elements

    DEFF Research Database (Denmark)

    Giuliani, Luisa; Budny, Iwona

    2010-01-01

    regulation in Europe, but it’s not easy to a-priori evaluate which is the safest or the most economical design due to the counterpoising effect of different requirements and assumption in the design procedures. A punctual analysis of the different aspects and a comparison of the resulting design is therefore...

  13. Regulating water pollution in China and the European Union in terms of agricultural pollution

    NARCIS (Netherlands)

    Dai, Liping|info:eu-repo/dai/nl/355129876

    2015-01-01

    Regulatory instruments, are the most commonly used policy instruments in both China and the EU. This article explores how China and the EU establish their water quality objectives by regulation and how they design implementation strategies, with a particular focus of agricultural water pollution

  14. The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H; de Vries, Peter J; Dep Farmaceutische wetenschappen; Sub Pharmacotherapy, Theoretical

    2014-01-01

    BACKGROUND: Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment

  15. Reconsidering the relevance of social license pressure and government regulation for environmental performance of European SMEs

    NARCIS (Netherlands)

    Graafland, Johan; Smid, Hugo

    Whereas social license pressure is held as a strong motive for the corporate social performance (CSP) of large enterprises, it is argued in literature that it will not sufficiently motivate small and medium-sized enterprises (SMEs). In this view, government regulation is the most effective way to

  16. sel-7, a positive regulator of lin-12 activity, encodes a novel nuclear protein in Caenorhabditis elegans.

    Science.gov (United States)

    Chen, Jiabin; Li, Xiajun; Greenwald, Iva

    2004-01-01

    Suppressor genetics in C. elegans has identified key components of the LIN-12/Notch signaling pathway. Here, we describe a genetic and molecular characterization of the suppressor gene sel-7. We show that reducing or eliminating sel-7 activity suppresses the effects of constitutive lin-12 activity, enhances the effects of partially reduced lin-12 activity, and causes a synthetic Lin-12(0) phenotype when combined with a null mutation in the sel-12 presenilin gene. These observations suggest that sel-7 is a positive regulator of lin-12 activity. We also show that SEL-7 encodes a novel nuclear protein. Through yeast two-hybrid screening, we identified an apparent interaction partner, K08E3.8, that also interacts with SEL-8, a known component of the nuclear complex that forms upon LIN-12 activation. Our data suggest potential roles for SEL-7 in the assembly or function of this nuclear complex.

  17. Barriers to access to opioid medicines: a review of national legislation and regulations of 11 central and eastern European countries.

    Science.gov (United States)

    Vranken, Marjolein J M; Lisman, John A; Mantel-Teeuwisse, Aukje K; Jünger, Saskia; Scholten, Willem; Radbruch, Lukas; Payne, Sheila; Schutjens, Marie-Hélène D B

    2016-01-01

    Control measures designed to prevent the misuse of opioid medicines can often unintentionally restrict legitimate medical use, leaving patients with cancer in pain. This study aimed to develop and validate an assessment instrument based on WHO policy guidelines to systematically identify legal and regulatory barriers to opioid access in 11 European countries (Bulgaria, Cyprus, Estonia, Greece, Hungary, Latvia, Lithuania, Serbia, Slovakia, Slovenia, and Turkey) as part of the Access to Opioid Medication in Europe project. Relevant legislation and regulations were independently assessed by three reviewers and potential barriers were identified within nine categories including prescribing, penalties, and others. Potential barriers were identified in all countries, ranging from 22 potential barriers (Cyprus) to 128 potential barriers (Lithuania). The total number of barriers in a single category varied from one (Slovenia, usage category) to 49 (Greece, prescribing category). Differences, such as prescription validity, varied within one category, ranging from 5 days (Hungary) to 13 weeks (Cyprus). The results of this Review should give rise to a national review and revision of provisions that impede access to opioids, disproportionate to their (intended) benefit in preventing misuse, in these 11 European countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. BIOCOMPATIBILITY OF MEDICAL DEVICES – LEGAL REGULATIONS IN THE EUROPEAN UNION.

    Directory of Open Access Journals (Sweden)

    Mariela Yaneva-Deliverska

    2015-02-01

    Full Text Available A multiplicity of laws, standards, and recommendations regulate the marketing of medical devices. Therefore, legal regulations do not release the specialists in the fields of medicine and dentistry from the responsibility to gather as much information as possible about the products used or to request this information from the manufacturer. Safety data sheets for medical devices can be downloaded from the Internet. They are an important source of information about the biocompatibility of dental materials as they were investigated by the manufacturers. Appropriate safety labels on the wrappings should be considered. The manufacturer/importer is responsible for its products and is potentially liable for damages. The medical doctors and dentists should use only those medical devices for which appropriate information is available.

  19. Molecular species identification of Central European ground beetles (Coleoptera: Carabidae using nuclear rDNA expansion segments and DNA barcodes

    Directory of Open Access Journals (Sweden)

    Raupach Michael J

    2010-09-01

    Full Text Available Abstract Background The identification of vast numbers of unknown organisms using DNA sequences becomes more and more important in ecological and biodiversity studies. In this context, a fragment of the mitochondrial cytochrome c oxidase I (COI gene has been proposed as standard DNA barcoding marker for the identification of organisms. Limitations of the COI barcoding approach can arise from its single-locus identification system, the effect of introgression events, incomplete lineage sorting, numts, heteroplasmy and maternal inheritance of intracellular endosymbionts. Consequently, the analysis of a supplementary nuclear marker system could be advantageous. Results We tested the effectiveness of the COI barcoding region and of three nuclear ribosomal expansion segments in discriminating ground beetles of Central Europe, a diverse and well-studied invertebrate taxon. As nuclear markers we determined the 18S rDNA: V4, 18S rDNA: V7 and 28S rDNA: D3 expansion segments for 344 specimens of 75 species. Seventy-three species (97% of the analysed species could be accurately identified using COI, while the combined approach of all three nuclear markers provided resolution among 71 (95% of the studied Carabidae. Conclusion Our results confirm that the analysed nuclear ribosomal expansion segments in combination constitute a valuable and efficient supplement for classical DNA barcoding to avoid potential pitfalls when only mitochondrial data are being used. We also demonstrate the high potential of COI barcodes for the identification of even closely related carabid species.

  20. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.

    Directory of Open Access Journals (Sweden)

    Daniël Splinter

    Full Text Available BICD2 is one of the two mammalian homologues of the Drosophila Bicaudal D, an evolutionarily conserved adaptor between microtubule motors and their cargo that was previously shown to link vesicles and mRNP complexes to the dynein motor. Here, we identified a G2-specific role for BICD2 in the relative positioning of the nucleus and centrosomes in dividing cells. By combining mass spectrometry, biochemical and cell biological approaches, we show that the nuclear pore complex (NPC component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle. BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry. When dynein function is suppressed by RNA interference-mediated depletion or antibody microinjection, centrosomes and nuclei are actively pushed apart in late G2 and we show that this is due to the action of kinesin-1. Surprisingly, depletion of BICD2 inhibits both dynein and kinesin-1-dependent movements of the nucleus and cytoplasmic NPCs, demonstrating that BICD2 is needed not only for the dynein function at the nuclear pores but also for the antagonistic activity of kinesin-1. Our study demonstrates that the nucleus is subject to opposing activities of dynein and kinesin-1 motors and that BICD2 contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1.

  1. Comparative Analysis of the Employee Protection Regulations for Transfer in the European and Romanian Legislation

    Directory of Open Access Journals (Sweden)

    Simona Petrina GAVRILA

    2011-11-01

    Full Text Available On the basis of mutual consent, regulating the legal employment relationships, the amendment of the individual employment contract is usually made by agreement of the parties. However, there are situations where the amendment concerning one of the parties of the employment relationship, such as the transfer of the company or part of the company, cause changes on this relationship, without the parties expressing their will in this way.

  2. Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals system-wide phosphorylation of transcriptional regulators

    DEFF Research Database (Denmark)

    Rabiee, Atefeh; Schwämmle, Veit; Sidoli, Simone

    2017-01-01

    . New insights into phosphorylation-dependent signaling networks that impact on nuclear proteins and controls adipocyte differentiation and cell fate. Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency...... are associated with adverse metabolic function. Adipogenesis is the process whereby preadipocyte precursor cells differentiate into lipid laden mature adipocytes. This process is driven by a network of transcriptional regulators (TRs). We hypothesized that protein post-translational modifications (PTMs...... levels of proteins involved in gene expression, cell organization, and oxidation-reduction pathways. Furthermore, proteins acting as negative modulators involved in negative regulation of gene expression, insulin stimulated glucose uptake, and cytoskeletal organization showed a decrease in their nuclear...

  3. Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Beildeck, Marcy E. [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States); Gelmann, Edward P. [Columbia University, Department of Medicine, New York, NY (United States); Byers, Stephen W., E-mail: byerss@georgetown.edu [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States)

    2010-07-01

    Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

  4. The Nuclear Matrix Protein Megator Regulates Stem Cell Asymmetric Division through the Mitotic Checkpoint Complex in Drosophila Testes.

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2015-12-01

    Full Text Available In adult Drosophila testis, asymmetric division of germline stem cells (GSCs is specified by an oriented spindle and cortically localized adenomatous coli tumor suppressor homolog 2 (Apc2. However, the molecular mechanism underlying these events remains unclear. Here we identified Megator (Mtor, a nuclear matrix protein, which regulates GSC maintenance and asymmetric division through the spindle assembly checkpoint (SAC complex. Loss of Mtor function results in Apc2 mis-localization, incorrect centrosome orientation, defective mitotic spindle formation, and abnormal chromosome segregation that lead to the eventual GSC loss. Expression of mitotic arrest-deficient-2 (Mad2 and monopolar spindle 1 (Mps1 of the SAC complex effectively rescued the GSC loss phenotype associated with loss of Mtor function. Collectively our results define a new role of the nuclear matrix-SAC axis in regulating stem cell maintenance and asymmetric division.

  5. Epigenetic Regulation of αA-crystallin in High Myopia-Induced Dark Nuclear Cataract

    Science.gov (United States)

    Zhang, Ke-Ke; Yang, Jin; Luo, Yi; Lu, Yi

    2013-01-01

    Purpose To assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA). Methods We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2–3; High-Myopic Cataract (HMC) NC2–3; ARC NC5–6; HMC NC5–6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry. Results The odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98–6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in the HMC NC5–6 Group exhibited the highest methylation of all the groups, but no statistically significant differences were evident between the HMC NC2–3 and ARC NC2–3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5–6 Group were significantly lower than the ARC NC5–6 Group and high-myopic controls. Conclusions High myopia is a risk factor for dark nucleus. Downregulation of CRYAA via the hypermethylation of CpG islands in its promoter could underlie the earlier onset of dark nucleus in high-myopic patients. PMID:24312600

  6. Regulation of viral and cellular gene expression by Kaposi's sarcoma-associated herpesvirus polyadenylated nuclear RNA.

    Science.gov (United States)

    Rossetto, Cyprian C; Tarrant-Elorza, Margaret; Verma, Subhash; Purushothaman, Pravinkumar; Pari, Gregory S

    2013-05-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma and body cavity lymphoma. In cell culture, KSHV results in a latent infection, and lytic reactivation is usually induced with the expression of K-Rta or by treatment with phorbol 12-myristate 13-acetate (TPA) and/or n-butyrate. Lytic infection is marked by the activation of the entire viral genomic transcription cascade and the production of infectious virus. KSHV-infected cells express a highly abundant, long, noncoding transcript referred to as polyadenylated nuclear RNA (PAN RNA). PAN RNA interacts with specific demethylases and physically binds to the KSHV genome to mediate activation of viral gene expression. A recombinant BACmid lacking the PAN RNA locus fails to express K-Rta and does not produce virus. We now show that the lack of PAN RNA expression results in the failure of the initiation of the entire KSHV transcription program. In addition to previous findings of an interaction with demethylases, we show that PAN RNA binds to protein components of Polycomb repression complex 2 (PRC2). RNA-Seq analysis using cell lines that express PAN RNA shows that transcription involving the expression of proteins involved in cell cycle, immune response, and inflammation is dysregulated. Expression of PAN RNA in various cell types results in an enhanced growth phenotype, higher cell densities, and increased survival compared to control cells. Also, PAN RNA expression mediates a decrease in the production of inflammatory cytokines. These data support a role for PAN RNA as a major global regulator of viral and cellular gene expression.

  7. Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury

    Directory of Open Access Journals (Sweden)

    Madiai Francesca

    2006-01-01

    Full Text Available Abstract Background NF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB. Results Immunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side. Conclusion ZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of

  8. Regulation of Nuclear Receptor Nur77 by miR-124.

    Directory of Open Access Journals (Sweden)

    Alexa Tenga

    Full Text Available The nuclear receptor Nur77 is commonly upregulated in adult cancers and has oncogenic functions. Nur77 is an immediate-early response gene that acts as a transcription factor to promote proliferation and protect cells from apoptosis. Conversely, Nur77 can translocate to the mitochondria and induce apoptosis upon treatment with various cytotoxic agents. Because Nur77 is upregulated in cancer and may have a role in cancer progression, it is of interest to understand the mechanism controlling its expression. MicroRNAs (miRNAs are responsible for inhibiting translation of their target genes by binding to the 3'UTR and either degrading the mRNA or preventing it from being translated into protein, thereby making these non-coding endogenous RNAs vital regulators of every cellular process. Several miRNAs have been predicted to target Nur77; however, strong evidence showing the regulation of Nur77 by any miRNA is lacking. In this study, we used a luciferase reporter assay containing the 3'UTR of Nur77 to screen 296 miRNAs and found that miR-124, which is the most abundant miRNA in the brain and has a role in promoting neuronal differentiation, caused the greatest reduction in luciferase activity. Interestingly, we discovered an inverse relationship in Daoy medulloblastoma cells and undifferentiated granule neuron precursors in which Nur77 is upregulated and miR-124 is downregulated. Exogenous expression to further elevate Nur77 levels in Daoy cells increased proliferation and viability, but knocking down Nur77 via siRNA resulted in the opposite phenotype. Importantly, exogenous expression of miR-124 reduced Nur77 expression, cell viability, proliferation, and tumor spheroid size in 3D culture. In all, we have discovered miR-124 to be downregulated in instances of medulloblastoma in which Nur77 is upregulated, resulting in a proliferative state that abets cancer progression. This study provides evidence for increasing miR-124 expression as a potential

  9. Synthetic biology regulation and governance: Lessons from TAPIC for the United States, European Union, and Singapore.

    Science.gov (United States)

    Trump, Benjamin D

    2017-11-01

    Synthetic biology is an emerging technology with potential benefits to various fields, yet also contains potential risks to human and environmental health. The field remains in an emerging state with limited quantitative guidance and a small but growing population of international researchers that conduct work within this field. Given the uncertain nature of this technology, an adaptive and anticipatory governance framework may be necessary to balance the potential benefits that may accrue from the technology's continued research alongside a desire to reduce or eliminate potential risks that may arise. However, such developments must account for the unique political and institutional factors that form a government's risk culture - something that can facilitate or impede the development of adaptive synthetic biology governance moving forward. The TAPIC framework helps illustrate those factors that are essential to develop good governance for emerging technologies like synthetic biology. Specifically, an application of TAPIC to synthetic biology governance indicates that the factors of accountability, participation, and integrity must be bolstered to improve technology governance in governments like with the United States, European Union, and Singapore. Copyright © 2017. Published by Elsevier B.V.

  10. Sixth Warren K. Sinclair keynote address: The role of a strong regulator in safe and secure nuclear energy.

    Science.gov (United States)

    Lyons, Peter B

    2011-01-01

    The history of nuclear regulation is briefly reviewed to underscore the early recognition that independence of the regulator was essential in achieving and maintaining public credibility. The current licensing process is reviewed along with the status of applications. Challenges faced by both the NRC and the industry are reviewed, such as new construction techniques involving modular construction, digital controls replacing analog circuitry, globalization of the entire supply chain, and increased security requirements. The vital area of safety culture is discussed in some detail, and its importance is emphasized. Copyright © 2010 Health Physics Society

  11. FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres - potential relevance to Alzheimer's disease.

    Science.gov (United States)

    Schrötter, Andreas; Mastalski, Thomas; Nensa, Fabian M; Neumann, Martin; Loosse, Christina; Pfeiffer, Kathy; Magraoui, Fouzi El; Platta, Harald W; Erdmann, Ralf; Theiss, Carsten; Uszkoreit, Julian; Eisenacher, Martin; Meyer, Helmut E; Marcus, Katrin; Müller, Thorsten

    2013-06-01

    The intracellular domain of the amyloid precursor protein (AICD) is generated following cleavage of the precursor by the γ-secretase complex and is involved in membrane to nucleus signaling, for which the binding of AICD to the adapter protein FE65 is essential. Here we show that FE65 knockdown causes a downregulation of the protein Bloom syndrome protein (BLM) and the minichromosome maintenance (MCM) protein family and that elevated nuclear levels of FE65 result in stabilization of the BLM protein in nuclear mobile spheres. These spheres are able to grow and fuse, and potentially correspond to the nuclear domain 10. BLM plays a role in DNA replication and repair mechanisms and FE65 was also shown to play a role in DNA damage response in the cell. A set of proliferation assays in our work revealed that FE65 knockdown in HEK293T cells reduced cell replication. On the basis of these results, we hypothesize that nuclear FE65 levels (nuclear FE65/BLM containing spheres) may regulate cell cycle re-entry in neurons as a result of increased interaction of FE65 with BLM and/or an increase in MCM protein levels. Thus, FE65 interactions with BLM and MCM proteins may contribute to the neuronal cell cycle re-entry observed in brains affected by Alzheimer's disease.

  12. Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells

    Directory of Open Access Journals (Sweden)

    Nikolai V. Kuznetsov

    2017-10-01

    Full Text Available Abstract Background The Wiskott–Aldrich syndrome protein (WASp family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq in thymocytes and spleen CD4+ T cells. Results WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. Conclusions These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.

  13. Regulation and binding of pregnane X receptor by nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT).

    Science.gov (United States)

    Johnson, David R; Li, Chia-Wei; Chen, Liuh-Yow; Ghosh, Jagadish C; Chen, J Don

    2006-01-01

    The pregnane X receptor (PXR) is an orphan nuclear receptor predominantly expressed in liver and intestine. PXR coordinates hepatic responses to prevent liver injury induced by environmental toxins. PXR activates cytochrome P450 3A4 gene expression upon binding to rifampicin (Rif) and clotrimazole (CTZ) by recruiting transcriptional coactivators. It remains unclear whether and how PXR regulates gene expression in the absence of ligand. In this study, we analyzed interactions between PXR and the silencing mediator of retinoid and thyroid hormone receptors (SMRT) and determined the role of SMRT in regulating PXR activity. We show that SMRT interacts with PXR in glutathione S-transferase pull-down, yeast two-hybrid, and mammalian two-hybrid assays. The interaction is mediated through the ligand-binding domain of PXR and the SMRTs' nuclear receptor-interacting domain 2. The PXR-SMRT interaction is sensitive to species-specific ligands, and Rif causes an exchange of the corepressor SMRT with the p160 coactivator known as receptor-associated coactivator 3 (RAC3). Deletion of the PXR's activation function 2 helix enhances SMRT binding and abolishes ligand-dependent dissociation of SMRT. Coexpression of PXR with SMRT results in colocalization at discrete nuclear foci. Finally, transient transfection assays show that overexpression of SMRT inhibits PXR's transactivation of the Cyp3A4 promoter, whereas silencing of SMRT enhances the reporter expression. Taken together, our results suggest that the corepressor SMRT may bind to and regulate the transcriptional activity of PXR.

  14. AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.

    Science.gov (United States)

    Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

    2014-01-01

    Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

  15. Star-PAP Control of BIK Expression and Apoptosis Is Regulated by Nuclear PIPKIα and PKCδ Signaling

    Science.gov (United States)

    Li, Weimin; Laishram, Rakesh S.; Ji, Zhe; Barlow, Christy A.; Tian, Bin; Anderson, Richard A.

    2012-01-01

    SUMMARY BIK protein is an initiator of mitochondrial apoptosis and BIK expression is induced by pro-apoptotic signals including DNA damage. Here we demonstrate that 3′-end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex and PKCδ activity is directly stimulated by PI4,5P2. Features in the BIK 3′-UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P2 and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3′-end processing. PMID:22244330

  16. Historical review of European gasoline lead content regulations and their impact on German industrial markets

    Energy Technology Data Exchange (ETDEWEB)

    Hagner, C. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Hydrophysik

    1999-07-01

    Environmental protection policies in the automobile market were not implemented until the motorisation of the masses in the 1960s caused an increasing environmental burden. The rising air pollution was considered a latent danger for humans, animals and plants. In the years up to 1985 the EU passed several regulations to limit the mass pollutants CO, CxHy and NOx. Germany was the first EU-member nation to also be concerned with lead in gasoline, passing reduction regulations as early as in 1971. In 1986, several EU-member nations implemented the supply of unleaded gasoline. This decision was predominantly based on information about widespread forest damage. The reduction of lead emissions due to these regulations could be verified in different environmental systems. An example of this was the decline of atmospheric lead concentrations and human blood lead levels in Germany. The German mineral oil and automobile markets were also affected. The price trend of unleaded fuel was heavily influenced by tax incentives which benefited not only the gasoline traders but also the consumers. With regard to the distribution system, the market positions particularly of the medium-sized traders and the independent importers were weakened. In the automobile market, favourable terms of competition were experienced by producers who had already gained experience with catalyst systems in the U.S.-market. The gasoline lead content regulations had no effects on further economic indicators, except for competition. (orig.) [German] Infolge der Massenmotorisierung in den 60er Jahren stieg die Umweltbelastung durch den Automobilverkehr stark an. Luftverschmutzung durch Kraftfahrzeuge wurde erstmalig als latente Gefahr fuer die Gesundheit von Mensch, Tier und Pflanze wahrgenommen. Dies charakterisierte den Beginn der Umweltpolitik im Automobilsektor. Bis 1985 verabschiedete die Europaeische Union (EU) mehrere Rahmenrichtlinien zur Reduktion der Luftschadstoffe CO, CxHy und NOx. 1971 war

  17. National report 2012 to the Agency for the cooperation of energy regulators and to the European Commission. Finland

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-15

    This is a national report prepared by the Energy Market Authority to the Agency for the Co-operation of Energy Regulators and the European Commission on the state of the Finnish electricity and natural gas markets in 2011 as required by Article 37 (1)(e) in the Directive for the Internal Market in Natural Gas (2009/73/EC). Although this is the first national report after the entry into force of the above-mentioned directives, the report continues the series of annual national reports published since 2004. The document covers the steps the Energy Market Authority has taken and the results obtained as regards each of the tasks listed in the Article 37 of the Electricity Market Directive and the Article 41 of Natural Gas Market Directive. It contains a description of the power and tasks of the regulatory authority, an overview of the regulation and performance of electricity and natural gas sectors and an update of security of supply with regard to both gas and electricity.

  18. Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism, liver regeneration, and hepatocarcinogenesis.

    Science.gov (United States)

    Jia, Yuzhi; Viswakarma, Navin; Reddy, Janardan K

    2014-01-01

    Several nuclear receptors regulate diverse metabolic functions that impact on critical biological processes, such as development, differentiation, cellular regeneration, and neoplastic conversion. In the liver, some members of the nuclear receptor family, such as peroxisome proliferator-activated receptors (PPARs), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), liver X receptor (LXR), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others, regulate energy homeostasis, the formation and excretion of bile acids, and detoxification of xenobiotics. Excess energy burning resulting from increases in fatty acid oxidation systems in liver generates reactive oxygen species, and the resulting oxidative damage influences liver regeneration and liver tumor development. These nuclear receptors are important sensors of exogenous activators as well as receptor-specific endogenous ligands. In this regard, gene knockout mouse models revealed that some lipid-metabolizing enzymes generate PPARα-activating ligands, while others such as ACOX1 (fatty acyl-CoA oxidase1) inactivate these endogenous PPARα activators. In the absence of ACOX1, the unmetabolized ACOX1 substrates cause sustained activation of PPARα, and the resulting increase in energy burning leads to hepatocarcinogenesis. Ligand-activated nuclear receptors recruit the multisubunit Mediator complex for RNA polymerase II-dependent gene transcription. Evidence indicates that the Med1 subunit of the Mediator is essential for PPARα, PPARγ, CAR, and GR signaling in liver. Med1 null hepatocytes fail to respond to PPARα activators in that these cells do not show induction of peroxisome proliferation and increases in fatty acid oxidation enzymes. Med1-deficient hepatocytes show no increase in cell proliferation and do not give rise to liver tumors. Identification of nuclear receptor-specific coactivators and Mediator subunits should further our understanding of the complexities of metabolic

  19. The potential role of Life Cycle Assessment in regulation of chemicals in the European Union

    DEFF Research Database (Denmark)

    Christensen, Frans Møller; Olsen, Stig Irving

    2003-01-01

    uses of LCA could be in overall priority setting (including non-chemical products) of environmental product policy and in standardisation work related to products/processes releasing chemicals to the environment. A number of methodological interactions between regulatory risk assessment and LCA as well...... for data and assessment procedures on dangerous chemicals. One change is the inclusion of socio-economic assessments as decision support to regulation of substances, which are undesirable from a risk assessment point of view. Comparative LCA’s have similarities with and may serve as good input to socio......-economic analyses, because LCA’s attempt to: 1. cover all emissions (including intermediates), 2. assess all potential environmental impacts, 3. assess the average situation (including uncertainty analyses). Contrary, risk assessments are based on substance approaches and conservative assumptions. Other potential...

  20. Survey of Regulations Applicable to the Finned Containment in Korean Nuclear Power Plant for Light Water Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Hyung Gyun [Pohang University, Pohang (Korea, Republic of); Kang, Hie Chan [Kunsan University, Gunsan (Korea, Republic of)

    2016-05-15

    In severe accident, the molten corium would discharge into the reactor cavity and interact with water and concrete of cavity. Molten corium includes non-oxidation metals such as Zr, Fe and Cr. These metal species reacted with water emit hydrogen gas. In addition to this, a mount of steam can be emitted to the containment such as steam line break accident. As a result, steam and hydrogen gas can pressurize containment over the design pressure and threaten its integrity. For this reasons, a concept equipped with finned on the containment building was proposed for coping with prolonged accident. Finned containment can enhance heat transfer to the ambient, and the building itself is working as a heat sink. Multiple metal fins and metal rod are penetrated into containment wall, and the rods are working as an additional path of heat removal. To be accepted in the nuclear power plants, this configuration should satisfy the requirement of heat removal and follow all regulations related with containment also. For applying to Korean nuclear power plants, the finned containment should follow all regulations specialized in Korea such as Nuclear regulatory criteria for light water reactor and Guidelines of nuclear safety examination for light water reactor. A concept of containment as a passive cooling system has been proposed. Furthermore, the new containment concept can be applied on the real containment which satisfies the various regulations. Finned containment would be expected positive effects on heat removal from the containment. If the fins are properly welded to the liner, finned containment could satisfy the leak tightness and prevention of external influences. Finned containment could be favorable to protect external impact like aircraft crash because of the additional structural integrity by the fins.

  1. Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Takeyoshi [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Asahi, Toru [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Sawamura, Naoya, E-mail: naoya.sawamura@gmail.com [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan)

    2016-08-26

    The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.

  2. Cofilin Regulates Nuclear Architecture through a Myosin-II Dependent Mechanotransduction Module

    OpenAIRE

    Wiggan, O?Neil; Schroder, Bryce; Krapf, Diego; Bamburg, James R.; DeLuca, Jennifer G.

    2017-01-01

    Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal ...

  3. Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN countries

    Directory of Open Access Journals (Sweden)

    Gluud Christian

    2012-03-01

    Full Text Available Abstract Background In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe. Methods We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries. Results Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised. Conclusion The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.

  4. European accomplishments in regulation of the family status of the child conceived by artificial reproduction technologies

    Directory of Open Access Journals (Sweden)

    Kovaček-Stanić Gordana

    2015-01-01

    transferring the nucleus of a somatic cell from one woman into an enucleated egg of another. In that case, the child would not have genetic father at all. Bearing in mind the new artificial reproduction technologies and their influence to legal rules of establishment of the family status of the child, it could be said that the legal principle of the autonomy of the parties is widened in comparison to material truth. People who wish to be parents become legal parents although they are not generic parents. Sometimes they cannot be genetic parents due to their infertility and sometimes because they are of the same sex. As a result of artificial reproduction technologies, a child could have a genetic link with one of the parents, only with a mother - in the heterologous insemination, only a father - as in egg donation and genetic surrogacy. The child could have genetic link with both of the parents - as in the gestational surrogacy, or it could have no genetic links with his/her legal parents - as in embryo donation. According to some European legislatures, it is possible for the child to have a mother and the other female parent, or a father and the other male parent. Surrogate mother, as well as donors of the genetic material, are not considered as parents. Radical change in social and individual perception of parenthood could accept the fact the child could have more than two parents with different roles (biological - genetic parents, gestational mother, social - legal parents.

  5. Nuclear trafficking of secreted factors and cell-surface receptors: new pathways to regulate cell proliferation and differentiation, and involvement in cancers

    Directory of Open Access Journals (Sweden)

    Planque Nathalie

    2006-10-01

    Full Text Available Abstract Secreted factors and cell surface receptors can be internalized by endocytosis and translocated to the cytoplasm. Instead of being recycled or proteolysed, they sometimes translocate to the nucleus. Nuclear import generally involves a nuclear localization signal contained either in the secreted factor or its transmembrane receptor, that is recognized by the importins machinery. In the nucleus, these molecules regulate transcription of specific target genes by direct binding to transcription factors or general coregulators. In addition to the transcription regulation, nuclear secreted proteins and receptors seem to be involved in other important processes for cell life and cellular integrity such as DNA replication, DNA repair and RNA metabolism. Nuclear secreted proteins and transmembrane receptors now appear to induce new signaling pathways to regulate cell proliferation and differentiation. Their nuclear localization is often transient, appearing only during certain phases of the cell cycle. Nuclear secreted and transmembrane molecules regulate the proliferation and differentiation of a large panel of cell types during embryogenesis and adulthood and are also potentially involved in wound healing. Secreted factors such as CCN proteins, EGF, FGFs and their receptors are often detected in the nucleus of cancer cells. Nuclear localization of these molecules has been correlated with tumor progression and poor prognosis for patient survival. Nuclear growth factors and receptors may be responsible for resistance to radiotherapy.

  6. Smad Nuclear Interacting Protein 1 Acts as a Protective Regulator of Pressure Overload-Induced Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    Lu, Yu-Yan; Xu, Da-Chun; Zhao, Yi-Fan; Zhu, Guo-Fu; Zhu, Meng-Yun; Liu, Wei-Jing; Yu, Xue-Jing; Chen, Wei; Liu, Zheng; Xu, Ya-Wei

    2016-10-26

    Smad nuclear interacting protein 1 (SNIP1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP1 in cardiac hypertrophy remains unclear. Here we examined the role of SNIP1 in pressure overload-induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding-induced mice hearts, and angiotensin II-treated cardiomyocytes. Accordingly, SNIP1 deficiency significantly exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and contractile dysfunction, whereas cardiac-specific overexpression of SNIP1 markedly recovered pressure overload-induced cardiac hypertrophy and fibrosis. Besides that, SNIP1 protected neonatal rat cardiomyocytes against angiotensin II-induced hypertrophy in vitro. Moreover, we identified that SNIP1 suppressed nuclear factor-κB signaling during pathological cardiac hypertrophy, and inhibition of nuclear factor-κB signaling by a cardiac-specific conditional inhibitor of κB S 32A/S36A transgene blocked these adverse effects of SNIP1 deficiency on hearts. Together, our findings demonstrated that SNIP1 had protective effects in pressure overload-induced pathological cardiac hypertrophy via inhibition of nuclear factor-κB signaling. Thus, SNIP1 may be a novel approach for the treatment of heart failure. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. Nekton response to freshwater inputs in a temperate European estuary with regulated riverine inflow.

    Science.gov (United States)

    González-Ortegón, E; Subida, M D; Arias, A M; Baldó, F; Cuesta, J A; Fernández-Delgado, C; Vilas, C; Drake, P

    2012-12-01

    The aim of this 12-year study was to assess the nekton (fish, decapod crustaceans) response to freshwater inputs (rainfall, dam discharges) in a temperate estuary with regulated riverine inflow. Although interannual variability in river discharges to the Guadalquivir estuary has been extremely high since the construction of a dam in 1930, a significant decreasing trend in the dam's discharges has been observed in the last 80 years. During this study, an alternation of wet, standard and dry years occurred in the estuarine area but no significant long-term trend was observed. River discharge, in turn, showed a considerable interannual variability and a significantly decreasing long-term trend. Freshwater inputs had an immediate effect on estuarine salinity and turbidity, and consequently on prey availability (mysids). Although 124 nektonic species were collected, only 47 of them (adding up to 99.7% of total abundance) were regularly present in the estuary: 32 marine migrants, 13 estuarine species and 2 diadromous species. Well-defined temporal changes in species composition and abundance yielded clear seasonal patterns in the estuarine nektonic community. Considerable intermonth and interannual changes were occasionally observed relating to freshwater inputs, mainly in winter/autumn of wet years. Thus, within each two-month period, some significant interannual differences in the nektonic community were also observed, with marine migrants tending to be more abundant in dry years. However, changes in the studied nektonic community did not show long-term trends. In conclusion, natural and human-controlled freshwater inputs currently play a significant role in determining the physicochemical conditions and the biota of the Guadalquivir estuary. However, although freshwater input seemed to transitorily affect the estuarine nekton, either directly (flushing out) or indirectly (through changes in salinity, turbidity and prey availability), a quick reestablishment of the

  8. Virtual nuclear envelope breakdown and its regulators in fission yeast meiosis

    Directory of Open Access Journals (Sweden)

    Haruhiko eAsakawa

    2016-02-01

    Full Text Available Ran, a small GTPase, is required for the spindle formation and nuclear envelope (NE formation. After NE breakdown (NEBD during mitosis in metazoan cells, the Ran-GTP gradient across the NE is lost and Ran-GTP becomes concentrated around chromatin, thus affecting the stability of microtubules and promoting the assembly of spindle microtubules and segregation of chromosomes. Mitosis in which chromosomes are segregated subsequent to NEBD is called open mitosis. In contrast, many fungi undergo a process termed closed mitosis in which chromosome segregation and spindle formation occur without NEBD. Although the fission yeast Schizosaccharomyces pombe undergoes a closed mitosis, it exhibits a short period during meiosis (anaphase of the second meiosis; called anaphase II when nuclear and cytoplasmic proteins are mixed in the presence of intact NE and nuclear pore complexes (NPC. This virtual nuclear envelope breakdown (vNEBD involves changes in the localization of RanGAP1, an activator of Ran-GTP hydrolysis. Recently, Nup132, a component of the structural core Nup107-160 subcomplex of the NPC, has been shown to be involved in the maintenance of the nuclear cytoplasmic barrier in yeast meiosis. In this review, we highlight the possible roles of RanGAP1 and Nup132 in vNEBD and discuss the biological significance of vNEBD in S. pombe meiosis.

  9. Recombinational DNA repair is regulated by compartmentalization of DNA lesions at the nuclear pore complex

    DEFF Research Database (Denmark)

    Géli, Vincent; Lisby, Michael

    2015-01-01

    The nuclear pore complex (NPC) is emerging as a center for recruitment of a class of "difficult to repair" lesions such as double-strand breaks without a repair template and eroded telomeres in telomerase-deficient cells. In addition to such pathological situations, a recent study by Su and colle......The nuclear pore complex (NPC) is emerging as a center for recruitment of a class of "difficult to repair" lesions such as double-strand breaks without a repair template and eroded telomeres in telomerase-deficient cells. In addition to such pathological situations, a recent study by Su...

  10. Risk-informed regulation and safety management of nuclear power plants--on the prevention of severe accidents.

    Science.gov (United States)

    Himanen, Risto; Julin, Ari; Jänkälä, Kalle; Holmberg, Jan-Erik; Virolainen, Reino

    2012-11-01

    There are four operating nuclear power plant (NPP) units in Finland. The Teollisuuden Voima (TVO) power company has two 840 MWe BWR units supplied by Asea-Atom at the Olkiluoto site. The Fortum corporation (formerly IVO) has two 500 MWe VVER 440/213 units at the Loviisa site. In addition, a 1600 MWe European Pressurized Water Reactor supplied by AREVA NP (formerly the Framatome ANP--Siemens AG Consortium) is under construction at the Olkiluoto site. Recently, the Finnish Parliament ratified the government Decision in Principle that the utilities' applications to build two new NPP units are in line with the total good of the society. The Finnish utilities, Fenno power company, and TVO company are in progress of qualifying the type of the new nuclear builds. In Finland, risk-informed applications are formally integrated in the regulatory process of NPPs that are already in the early design phase and these are to run through the construction and operation phases all through the entire plant service time. A plant-specific full-scope probabilistic risk assessment (PRA) is required for each NPP. PRAs shall cover internal events, area events (fires, floods), and external events such as harsh weather conditions and seismic events in all operating modes. Special attention is devoted to the use of various risk-informed PRA applications in the licensing of Olkiluoto 3 NPP. © 2012 Society for Risk Analysis.

  11. Summary report on transportation of nuclear fuel materials in Japan : transportation infrastructure, threats identified in open literature, and physical protection regulations.

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John Russell; Ouchi, Yuichiro (Japan Atomic Energy Agency, Japan); Furaus, James Phillip; Marincel, Michelle K.

    2008-03-01

    This report summarizes the results of three detailed studies of the physical protection systems for the protection of nuclear materials transport in Japan, with an emphasis on the transportation of mixed oxide fuel materials1. The Japanese infrastructure for transporting nuclear fuel materials is addressed in the first section. The second section of this report presents a summary of baseline data from the open literature on the threats of sabotage and theft during the transport of nuclear fuel materials in Japan. The third section summarizes a review of current International Atomic Energy Agency, Japanese and United States guidelines and regulations concerning the physical protection for the transportation of nuclear fuel materials.

  12. A Noninvasive Method to Study Regulation of Extracellular Fluid Volume in Rats Using Nuclear Magnetic Resonance

    Science.gov (United States)

    Time-domain nuclear magnetic resonance (TD-NMR)-based measurement of body composition of rodents is an effective method to quickly and repeatedly measure proportions of fat, lean, and fluid without anesthesia. TD-NMR provides a measure of free water in a living animal, termed % f...

  13. International Cooperation in the Area of Nuclear Safety Regulation: Current Status and Way Forward

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, J. W.; Byeon, M. J.; Lee, J. M.; Lim, J. H. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2016-10-15

    Global effort and initiatives undertaken after the Fukushima Daiichi accident was the adoption of the Vienna Declaration on Nuclear Safety in February 2015. The Contracting Parties to the Convention on Nuclear Safety (CNS) collaboratively prepared the documentation of the Declaration and unanimously adopted it with the idea to prevent accidents with radiological consequences and to mitigate such consequences should they occur. The OECD/NEA has been working closely with its member and partner countries to identify lessons learnt and follow-up actions at the national and international levels so as to maintain and enhance the level of safety at nuclear facilities following the Fukushima Daiichi nuclear power plant accident. In 2013, the NEA published a report entitled The Fukushima Daiichi Nuclear Power Plant Accident: OECD/NEA Nuclear Safety Response and Lessons Learnt detailing the key immediate responses of the NEA and its member countries. Subsequent to the publish of the report and based on the lessons presented, NEA published a new report entitled Five Years after the Fukushima Daiichi Accident: Nuclear Safety Improvements and Lessons Learnt, focusing on what has been done by the Agency and its member countries to improve safety since the accident in 2011. cooperation based on the needs of technical area would further enhance effectiveness of cooperative activities and would enable to foresee future regulatory needs which can be considered when establishing a strategy. Since the establishment of NSSC in 2011, NSSC has played a major role in concluding agreements with regulatory bodies of other countries. Despite of the change, KINS, yet, is able to pursue technical-specified cooperation as a TSO under the umbrella of agreements between governments or regulatory bodies. establishment of expert pool and systematic mid- and long-term capacity building framework of relevant experts would enhance continuity and expertise. Currently, most of the participants or

  14. Autophagy contributes to regulation of nuclear dynamics during vegetative growth and hyphal fusion in Fusarium oxysporum.

    Science.gov (United States)

    Corral-Ramos, Cristina; Roca, M Gabriela; Di Pietro, Antonio; Roncero, M Isabel G; Ruiz-Roldán, Carmen

    2015-01-01

    In the fungal pathogen Fusarium oxysporum, vegetative hyphal fusion triggers nuclear mitotic division in the invading hypha followed by migration of a nucleus into the receptor hypha and degradation of the resident nucleus. Here we examined the role of autophagy in fusion-induced nuclear degradation. A search of the F. oxysporum genome database for autophagy pathway components identified putative orthologs of 16 core autophagy-related (ATG) genes in yeast, including the ubiquitin-like protein Atg8, which is required for the formation of autophagosomal membranes. F. oxysporum Foatg8Δ mutants were generated in a strain harboring H1-cherry fluorescent protein (ChFP)-labeled nuclei to facilitate analysis of nuclear dynamics. The Foatg8Δ mutants did not show MDC-positive staining in contrast to the wild type and the FoATG8-complemented (cFoATG8) strain, suggesting that FoAtg8 is required for autophagy in F. oxysporum. The Foatg8Δ strains displayed reduced rates of hyphal growth, conidiation, and fusion, and were significantly attenuated in virulence on tomato plants and in the nonvertebrate animal host Galleria mellonella. In contrast to wild-type hyphae, which are almost exclusively composed of uninucleated hyphal compartments, the hyphae of the Foatg8Δ mutants contained a significant fraction of hyphal compartments with 2 or more nuclei. The increase in the number of nuclei per hyphal compartment was particularly evident after hyphal fusion events. Time-lapse microscopy analyses revealed abnormal mitotic patterns during vegetative growth in the Foatg8Δ mutants. Our results suggest that autophagy mediates nuclear degradation after hyphal fusion and has a general function in the control of nuclear distribution in F. oxysporum.

  15. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    Energy Technology Data Exchange (ETDEWEB)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  16. MicroRNA-144 Regulates Hepatic ABCA1 and Plasma HDL Following Activation of the Nuclear Receptor FXR

    Science.gov (United States)

    de Aguiar Vallim, Thomas Q.; Tarling, Elizabeth J.; Kim, Tammy; Civelek, Mete; Baldán, Ángel; Esau, Christine; Edwards, Peter A.

    2014-01-01

    Rationale The bile acid receptor Farnesoid-X-Receptor (FXR) regulates many aspects of lipid metabolism by various complex and not fully understood molecular mechanisms. We set out to investigate the molecular mechanisms for FXR-dependent regulation of lipid and lipoprotein metabolism. Objective To identify FXR-regulated microRNAs that were subsequently involved in regulating lipid metabolism. Methods and Results ATP binding cassette transporter A1 (ABCA1) is a major determinant of plasma High Density Lipoprotein (HDL)-cholesterol levels. Here we show that activation of the nuclear receptor FXR in vivo increases hepatic levels of miR-144, which in turn lower hepatic ABCA1 and plasma HDL levels. We identified two complementary sequences to miR-144 in the 3′ untranslated region (UTR) of ABCA1 mRNA that are necessary for miR-144-dependent regulation. Overexpression of miR-144 in vitro decreased both cellular ABCA1 protein and cholesterol efflux to lipid-poor apolipoprotein A-I (ApoA-I) protein, whilst overexpression in vivo reduced hepatic ABCA1 protein and plasma HDL-cholesterol. Conversely, silencing miR-144 in mice increased hepatic ABCA1 protein and HDL-cholesterol. In addition, we utilized tissue-specific FXR deficient mice to show that induction of miR-144 and FXR-dependent hypolipidemia requires hepatic, but not intestinal FXR. Finally, we identified functional FXR response elements (FXREs) upstream of the miR-144 locus, consistent with direct FXR regulation. Conclusion We have identified a novel pathway involving FXR, miR-144 and ABCA1 that together regulate plasma HDL cholesterol. PMID:23519696

  17. Proliferating cell nuclear antigen (PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.

    Directory of Open Access Journals (Sweden)

    Bo Xu

    Full Text Available Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA, a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer granulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.

  18. The Regulation Framework for the Banking Sector: The EMU, European Banks and Rating Agencies before and during the Recent Financial and Debt Crisis

    Directory of Open Access Journals (Sweden)

    Eleftherios Thalassinos

    2012-05-01

    Full Text Available A regulation framework for the banking sector should be characterised by transparency,responsibility and performance in several important areas. These areas are the global and Europeanframework for corporate financial reporting (CFR, risk management (RM, stockholder value creation(SVC, corporate governance (CG, corporate social responsibility (CSR and sustainable development (SD.The regulation framework for the banking sector must also consider the fiscal and monetary environment inwhich a banking institution operates. The global rating system and the rating agencies will also have animportant impact on any regulation framework for the banking sector. These two factors play a key role whena financial, credit or debt crisis occurs. In this article, a holistic regulation framework for the banking sector ispresented. The article is based on European banks that are part of the European Monetary Union (EMU.Initially, it focuses on the timelines and review the integration of the European Monetary Union, relevantlegislation and information on member countries’ banking sectors. This information creates the frameworkfor the proposed model. The article considers all of the above factors in creating a holistic regulationframework for the banking sector to present in the context of the recent financial, credit and debt crises thathave taken place in the EMU.

  19. Why European and United States drug regulators are not speaking with one voice on anti-influenza drugs: regulatory review methodologies and the importance of 'deep' product reviews.

    Science.gov (United States)

    Mulinari, Shai; Davis, Courtney

    2017-11-09

    Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza. In Europe, Relenza was evaluated via the so-called national procedure with Sweden as the reference country. We show that FDA reviewers, unlike their European (i.e. Swedish) counterpart, (1) rejected the manufacturer's insistence on pooling efficacy data, (2) remained wary of subgroup analyses, and (3) insisted on stringent statistical analyses. These differences meant that the FDA was less likely to depart from prevailing regulatory and scientific standards in interpreting trial results. We argue that the differences are explained largely by divergent institutionalised review methodologies, i.e. the European regulator's reliance on manufacturer-compiled summaries compared to the FDA's examination of original data and documentation from trials. The FDA's more probing and meticulous evaluative methodology allowed its reviewers to develop 'deep' knowledge concerning the clinical and statistical facets of trials, and more informed opinions regarding suitable methods for analysing trial results. These findings challenge the current emphasis on evaluating regulatory performance mainly in terms of speed of review. We propose that persistent uncertainty and knowledge deficits regarding NIs could have been ameliorated had regulators engaged in the public debates over the drugs' efficacy and

  20. A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation.

    Science.gov (United States)

    Omori, Sayaka; Tanabe, Hideyuki; Banno, Kimihiko; Tsuji, Ayumi; Nawa, Nobutoshi; Hirata, Katsuya; Kawatani, Keiji; Kokubu, Chikara; Takeda, Junji; Taniguchi, Hidetoshi; Arahori, Hitomi; Wada, Kazuko; Kitabatake, Yasuji; Ozono, Keiichi

    2017-04-10

    Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architecture at different levels, which is normally optimised to maintain the physiological balance of gene expression. However, it has not been clearly elucidated whether and how aberrant configuration of chromosomes affects gene activities. To investigate the effects of trisomy 21 on nuclear organisation and gene expression, we performed three-dimensional fluorescent imaging analysis of chromosome-edited human induced pluripotent stem cells (iPSCs), which enabled identification of the parental origin of the three copies of chromosome 21. We found that two copies of maternal chromosomes resulting from meiotic nondisjunction had a higher tendency to form an adjacent pair and were located relatively distant from the nuclear membrane, suggesting the conserved interaction between these homologous chromosomes. Transcriptional profiling of parental-origin-specific corrected disomy 21 iPSC lines indicated upregulated expression of the maternal alleles for a group of genes, which was accompanied by a fluctuating expression pattern. These results suggest the unique effects of a pair of maternal chromosomes in trisomy 21, which may contribute to the pathological phenotype.

  1. Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the Regulation of Energy and Glucose Homeostasis.

    Science.gov (United States)

    Guillaume, Maeva; Montagner, Alexandra; Fontaine, Coralie; Lenfant, Françoise; Arnal, Jean-François; Gourdy, Pierre

    2017-01-01

    Estrogen receptor alpha (ERα) has been demonstrated to play a key role in reproduction but also to exert numerous functions in nonreproductive tissues. Accordingly, ERα is now recognized as a key regulator of energy homeostasis and glucose metabolism and mediates the protective effects of estrogens against obesity and type 2 diabetes. This chapter attempts to summarize our current understanding of the mechanisms of ERα activation and their involvement in the modulation of energy balance and glucose metabolism. We first focus on the experimental studies that constitute the basis of the understanding of ERα as a nuclear receptor and more specifically on the key roles played by its two activation functions (AFs). We depict the consequences of the selective inactivation of these AFs in mouse models, which further underline the prominent role of nuclear ERα in the prevention of obesity and diabetes, as on the reproductive tract and the vascular system. Besides these nuclear actions, a fraction of ERα is associated with the plasma membrane and activates nonnuclear signaling from this site. Such rapid effects, called membrane-initiated steroid signals (MISS), have been characterized in a variety of cell lines and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS as well as the generation of mice expressing an ERα protein impeded for membrane localization has just begun to unravel the physiological role of MISS in vivo and their contribution to ERα-mediated metabolic protection. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators.

  2. Regulation of hepatitis C virus replication by nuclear translocation of nonstructural 5A protein and transcriptional activation of host genes.

    Science.gov (United States)

    Maqbool, Muhammad Ahmad; Imache, Mohamed R; Higgs, Martin R; Carmouse, Sophie; Pawlotsky, Jean-Michel; Lerat, Hervé

    2013-05-01

    Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is involved in regulating viral replication through its direct interaction with the HCV RNA-dependent RNA polymerase. NS5A also alters infected cell metabolism through complex interactions with numerous host cell proteins. NS5A has furthermore been suggested to act as a transcriptional activator, although the impact on viral replication is unclear. To study this, HCV NS5A variants were amplified from hepatic tissue from an HCV-infected patient, and their abilities to activate gene transcription were analyzed in a single-hybrid yeast (Saccharomyces cerevisiae) model. Different variants isolated from the same patient displayed different transactivational activities. When these variants were inserted into the HCV subgenomic replicon system, they demonstrated various levels of RNA replication, which correlated with their transactivational activities. We showed that the C-terminal fragment of NS5A was localized to the nucleus and that a functional NS5A nuclear localization signal and cellular caspase activity were required for this process. Furthermore, nuclear localization of NS5A was necessary for viral replication. Finally, we demonstrate that nuclear NS5A binds to host cell promoters of several genes previously identified as important for efficient HCV RNA replication, inducing their transcription. Taken together, these results demonstrate a new mechanism by which HCV modulates its cellular environment, thereby enhancing viral replication.

  3. Spatial Position Regulates Power of Tryptophan: Discovery of a Major-Groove-Specific Nuclear-Localizing, Cell-Penetrating Tetrapeptide.

    Science.gov (United States)

    Bhunia, Debmalya; Mondal, Prasenjit; Das, Gaurav; Saha, Abhijit; Sengupta, Pallabi; Jana, Jagannath; Mohapatra, Saswat; Chatterjee, Subhrangsu; Ghosh, Surajit

    2018-01-24

    Identification of key amino acids is required for development of efficient cell-penetrating peptides (CPPs) and has tremendous implications in medicine. Extensive research work has enlightened us about the importance of two amino acids, arginine and tryptophan, in cell penetration. Here, we present a top-down approach to show how spatial positions of two tryptophans regulate the cellular entry and nuclear localization. This enables us to develop short, non-toxic tetrapeptides with excellent potential for cell penetration and nuclear localization. Among them, Glu-Thr-Trp-Trp (ETWW) emerges as the most promising. Results suggest that it enters into cancer cells following an endocytic pathway and binds at the major groove of nuclear DNA, where successive tryptophan plays major role. We subsequently show that it is not a P-glycoprotein substrate and is non-toxic to PC12-derived neurons, suggesting its excellent potential as a CPP. Furthermore, its potential as a CPP is validated in multi-cellular 3D cell culture (spheroid) and in in vivo mice model. This study provides major fundamental insights about the positional importance of tryptophan and opens new avenues toward the development of next-generation CPPs and major-groove-specific anticancer drugs.

  4. Comparison of legislation, regulations and national health strategies for palliative care in seven European countries (Results from the Europall Research Group): a descriptive study

    Science.gov (United States)

    2013-01-01

    Background According to EU policy, anyone in need of palliative care should be able to have access to it. It is therefore important to investigate which palliative care topics are subject to legislation and regulations in Europe and how these are implemented in (national) health care plans. This paper aims to deliver a structured overview of the legislation, existing regulations and the different health care policies regarding palliative care in seven European countries. Methods In 2008 an inventory of the organisation of palliative care was developed by the researchers of the Europall project. Included were two open questions about legislation, regulations, and health policy in palliative care. This questionnaire was completed using palliative care experts selected from Belgium, England, France, Germany, the Netherlands, Poland and Spain. Additionally, (grey) literature on palliative care health policy and regulations from the participating countries was collected to complete the inventory. Comparative analysis of country specific information was performed afterwards. Results In all countries palliative care regulations and policies existed (either in laws, royal decrees, or national policies). An explicit right to palliative care was mentioned in the Belgium, French and German law. In addition, access to palliative care was mentioned by all countries, varying from explicit regulations to policy intentions in national plans. Also, all countries had a national policy on palliative care, although sometimes mainly related to national cancer plans. Differences existed in policy regarding palliative care leave, advance directives, national funding, palliative care training, research, opioids and the role of volunteers. Conclusions Although all included European countries have policies on palliative care, countries largely differ in the presence of legislation and regulations on palliative care as well as the included topics. European healthcare policy recommendations

  5. Fast and high-energy neutron detection with nuclear track detectors: Results of the European joint experiments 1992/93

    Energy Technology Data Exchange (ETDEWEB)

    Schraube, H. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany); Alberts, W.G. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany); Weeks, A.R. [comps.] [Nuclear Electric plc, Berkeley (United Kingdom). Berkeley Technology Centre

    1997-12-31

    Under the auspices of EURADOS, the European radiation dosimetry group, seventeen recognised laboratories engaged in the field of individual neutron dosimetry with passive track detectors participated in an international comparative experiment. A number of twenty-seven detector systems, predominantly etched track detectors with the material PADC (poly allyl diglycol carbonate), were employed by the participating laboratories. Quasi-monoenergetic neutrons were provided for irradiations free-in-air and on front of a PMMA phantom by the GSF (Forschungszentrum fuer Umwelt und Gesundheit, Neuherberg, Germany) and by the PTB (Physikalisch-Technische Bundesanstalt, Braunschweig, Germany). High energy irradiations were conducted by the PSI (Paul-Scherrer Institut, Villigen, Switzerland). The results of the on-phantom irradiations were used to derive energy and angular responses of the track detectors, those of the free-in-air irradiations to obtain data for the linearity characteristics of the response with dose. The report contains a short description and the original data of the participating laboratories, displays the irradiation and reference conditions, and provides an over-all evaluation. Emphasis is placed on the quantitative evaluation of the background characteristics and of the non-linearity observed with most of the systems employed which limits their useful dose-range of application. (orig.)

  6. Overview of the European Union fusion nuclear technologies development and essential elements on the way to DEMO

    Energy Technology Data Exchange (ETDEWEB)

    Andreani, R. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany)]. E-mail: roberto.andreani@tech.efda.org; Diegele, E. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany); Gulden, W. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany); Laesser, R. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany); Maisonnier, D. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany); Murdoch, D. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany); Pick, M. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany); Poitevin, Y. [EFDA Close Support Unit, Boltzmannstr. 2, D-85740 Garching (Germany)

    2006-02-15

    EU is strongly preparing ITER construction involving the system of EU Associations, universities and industry. The European programme has been steered to be in line with the present conception of a future power reactor. Thirty percent of the fusion research budget has been spent on long-term related activities managed by EFDA. These include Power Plant Conceptual Studies (PPCS), the recently undertaken DEMO Conceptual Studies, design and R and D for breeder blankets, low activation materials and IFMIF. Developments on fuel cycle, neutronics, safety and socio-economics complement those specifically performed for ITER. Two EU helium-cooled DEMO blankets will be tested in ITER, using liquid lithium-lead and solid ceramics as breeders. The blanket structures will use EUROFER. Irradiations to 70-80 dpa will qualify EUROFER for DEMO. Advanced materials, in particular SiC{sub f}/SiC, under development, could provide more thermodynamically efficient blankets. Even with a fully successful ITER, a number of issues will remain open in technology. The application of high temperature superconductors, essential progress in materials, blanket design and remote handling, are required to produce environmentally safe and economically competitive fusion. A fully integrated world wide international programme is the best way to efficiently progress in these fields.

  7. The nuclear transcription factor PKNOX2 is a candidate gene for substance dependence in European-origin women.

    Directory of Open Access Journals (Sweden)

    Xiang Chen

    2011-01-01

    Full Text Available Substance dependence or addiction is a complex environmental and genetic disorder that results in serious health and socio-economic consequences. Multiple substance dependence categories together, rather than any one individual addiction outcome, may explain the genetic variability of such disorder. In our study, we defined a composite substance dependence phenotype derived from six individual diagnoses: addiction to nicotine, alcohol, marijuana, cocaine, opiates or other drugs as a whole. Using data from several genomewide case-control studies, we identified a strong (Odds ratio  = 1.77 and significant (p-value = 7E-8 association signal with a novel gene, PBX/knotted 1 homeobox 2 (PKNOX2, on chromosome 11 with the composite phenotype in European-origin women. The association signal is not as significant when individual outcomes for addiction are considered, or in males or African-origin population. Our findings underscore the importance of considering multiple addiction types and the importance of considering population and gender stratification when analyzing data with heterogeneous population.

  8. Disease modeling using embryonic stem cells: MeCP2 regulates nuclear size and RNA synthesis in neurons.

    Science.gov (United States)

    Yazdani, Morteza; Deogracias, Rubén; Guy, Jacky; Poot, Raymond A; Bird, Adrian; Barde, Yves-Alain

    2012-10-01

    Mutations in the gene encoding the methyl-CpG-binding protein MECP2 are the major cause of Rett syndrome, an autism spectrum disorder mainly affecting young females. MeCP2 is an abundant chromatin-associated protein, but how and when its absence begins to alter brain function is still far from clear. Using a stem cell-based system allowing the synchronous differentiation of neuronal progenitors, we found that in the absence of MeCP2, the size of neuronal nuclei fails to increase at normal rates during differentiation. This is accompanied by a marked decrease in the rate of ribonucleotide incorporation, indicating an early role of MeCP2 in regulating total gene transcription, not restricted to selected mRNAs. We also found that the levels of brain-derived neurotrophic factor (BDNF) were decreased in mutant neurons, while those of the presynaptic protein synaptophysin increased at similar rates in wild-type and mutant neurons. By contrast, nuclear size, transcription rates, and BDNF levels remained unchanged in astrocytes lacking MeCP2. Re-expressing MeCP2 in mutant neurons rescued the nuclear size phenotype as well as BDNF levels. These results reveal a new role of MeCP2 in regulating overall RNA synthesis in neurons during the course of their maturation, in line with recent findings indicating a reduced nucleolar size in neurons of the developing brain of mice lacking Mecp2. Copyright © 2012 AlphaMed Press.

  9. Optimization process for the design of the DCLL blanket for the European DEMOnstration fusion reactor according to its nuclear performances

    Science.gov (United States)

    Palermo, Iole; Rapisarda, David; Fernández-Berceruelo, Iván; Ibarra, Angel

    2017-07-01

    The research study focuses on the neutronic design analysis and optimization of one of the options for a fusion reactor designed as DCLL (dual coolant lithium-lead). The main objective has been to develop an efficient and technologically viable modular DCLL breeding blanket (BB) using the DEMO generic design specifications established within the EUROfusion Programme. The final neutronic design has to satisfy the requirements of: tritium self-sufficiency; BB thermal efficiency; preservation of plasma confinement; temperature limits imposed by materials; and radiation limits to guarantee the largest operational life for all the components. Therefore, a 3D fully heterogeneous DCLL neutronic model has been developed for the DEMO baseline 2014 determining its behaviour under the real operational conditions of the DEMO reactor. Consequent actions have been adopted to improve its performances. Neutronic assessments have specially addressed tritium breeding ratio, multiplication energy factor, power density distributions, damage and shielding responses. The model has then been adapted to the subsequent DEMO baseline 2015 (with a more powerful and bigger plasma, smaller divertor and bigger blanket segments), implying new design choices to improve the reactor nuclear performances.

  10. Nuclear-Cytoplasmic Trafficking of NTF2, the Nuclear Import Receptor for the RanGTPase, Is Subjected to Regulation: e42501

    National Research Council Canada - National Science Library

    Shawn C Chafe; Jacqueline B Pierce; Dev Mangroo

    2012-01-01

    .... Treatment of mammalian cells with polysorbitan monolaurate was found to inhibit nuclear export of tRNA and proteins, which are processes dependent on RanGTP in the nucleus, but not nuclear import...

  11. [Outlook and problems of microbiological sampling in public catering establishments in light of the new European regulations].

    Science.gov (United States)

    Amadei, Paolo; Biondi, Augusto; Tarsitani, Gianfranco; Antonini, Alessandra

    2008-01-01

    Modern society is structured in such a way that more food is eaten outside the home and therefore the hygienic standards of food production and organoleptic characteristics of foods provided by catering establishments is of increasing importance. In order to obtain a complete view of the hygienic standards of the food production cycle, however, it is not sufficient to show that pathogenic microroganisms are absent, but it is also useful to measure the number of microroganisms which do not constitute a hazard to health but whose presence may alter the quality of food products or be an index of inadequate hygienic practices. Microbiological testing plays a fundamental role in the evaluation of the quality of a food product and according to the Codex Alimentarius, limits should be set based on absolute criteria, according to legislation requirements or on relative criteria based on contamination trends over time within the production process The new European food hygiene regulations CE 852/04 e 2073/05 promote a more advanced and correct view of microbiological controls, with respect to pre-existing national legislation, placing emphasis also on the production process of foodstuffs and not only on the final product. In addition, controls are explicitly considered as a tool to verify that food business operators comply with hygiene requirements. The aim of evaluating microbiological data should be to assess trends in the various analytical parameters and search for possible contamination indicators, in order to perform a thorough analysis based on inspections that evaluate the efficacy of food safety procedures put in place by food business operators, with sampling aimed at verifying quick simple and low cost index parameters Regarding the interpretation of collected data it should be underscored that the presence of a large variability points to presence of inadequate hygiene procedures, considering that the main obligation of each food business operator is to put in

  12. Financial re-regulation at a crossroads: How the European experience strengthens the case for a radical reform built on Minsky’s approach

    Directory of Open Access Journals (Sweden)

    Elisabetta Montanaro

    2012-12-01

    Full Text Available The current financial and sovereign crisis is pushing European politicians and EU bureaucrats to devise new institutional and policy solutions. However, the new EU institutional framework and stricter regulatory requirements do not introduce significant changes in the laissez-faire nature of the regulatory approach. Our opinion is that the entire re-regulation process does not go to the roots of how financial fragility endogenously accumulates, and how finally it produces a crisis each time starting from the weakest part of the financial system. Analysing the European banking sectors from this perspective, we show how domestic specificities add to the limits due to risk-based regulation and supervision. We then build on Minsky’s regulatory proposals to present the skeleton of a simple alternative to the existing regulatory approach.

  13. Communal sewage sludge treatement against the background of the new European Sewage Sludge Treatment Regulations; Kommunale Klaerschlammbehandlung vor dem Hintergrund der neuen Europaeischen Klaerschlammrichtlinien

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    The following issues were discussed at the Darmstadt conference: The European Sewage Sludge Treatment Regulation, hygienisation of sewage sludge, waste water purification without excess sludge production, stabilisation of sewage sludge, dewatering and disposal by combustion or utilisation as an agricultural fertilizer. [German] Themen des Darmstaedter Seminars Abwassertechnik waren: Europaeische Klaerschlammrichtlinie, Klaerschlammhygienisierung, Abwasserreinigung ohne Anfall von Ueberschussschlamm, Klaerschlammstabilisierung, Entwaesserung und Entsorgung durch Verbrennung oder in der Landwirtschaft. (UKE)

  14. The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading.

    Science.gov (United States)

    Tarallo, Roberta; Giurato, Giorgio; Bruno, Giuseppina; Ravo, Maria; Rizzo, Francesca; Salvati, Annamaria; Ricciardi, Luca; Marchese, Giovanna; Cordella, Angela; Rocco, Teresa; Gigantino, Valerio; Pierri, Biancamaria; Cimmino, Giovanni; Milanesi, Luciano; Ambrosino, Concetta; Nyman, Tuula A; Nassa, Giovanni; Weisz, Alessandro

    2017-10-06

    The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Applying interaction proteomics coupled to mass spectrometry to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association with a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ + vs ERβ - cells, and before and after AGO2 knock-down in ERβ + cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may also be able to directly control mRNA translation efficiency and stability. These results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions.

  15. Regulation of Liver Energy Balance by the Nuclear Receptors Farnesoid X Receptor and Peroxisome Proliferator Activated Receptor α.

    Science.gov (United States)

    Kim, Kang Ho; Moore, David D

    2017-01-01

    The liver undergoes major changes in substrate utilization and metabolic output over the daily feeding and fasting cycle. These changes occur acutely in response to hormones such as insulin and glucagon, with rapid changes in signaling pathways mediated by protein phosphorylation and other post-translational modifications. They are also reflected in chronic alterations in gene expression in response to nutrient-sensitive transcription factors. Among these, the nuclear receptors farnesoid X receptor (FXR) and peroxisome proliferator activated receptor α (PPARα) provide an intriguing, coordinated response to maintain energy balance in the liver. FXR is activated in the fed state by bile acids returning to the liver, while PPARα is activated in the fasted state in response to the free fatty acids produced by adipocyte lipolysis or possibly other signals. Key Messages: Previous studies indicate that FXR and PPARα have opposing effects on each other's primary targets in key metabolic pathways including gluconeogenesis. Our more recent work shows that these 2 nuclear receptors coordinately regulate autophagy: FXR suppresses this pathway of nutrient and energy recovery, while PPARα activates it. Another recent study indicates that FXR activates the complement and coagulation pathway, while earlier studies identify this as a negative target of PPARα. Since secretion is a very energy- and nutrient-intensive process for hepatocytes, it is possible that FXR licenses it in the nutrient-rich fed state, while PPARα represses it to spare resources in the fasted state. Energy balance is a potential connection linking FXR and PPARα regulation of autophagy and secretion, 2 seemingly unrelated aspects of hepatocyte function. FXR and PPARα act coordinately to promote energy balance and homeostasis in the liver by regulating autophagy and potentially protein secretion. It is quite likely that their impact extends to additional pathways relevant to hepatic energy balance, and

  16. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

    Science.gov (United States)

    Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-11-24

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

  17. Liver X receptor regulates hepatic nuclear O-GlcNAc signaling and carbohydrate responsive element-binding protein activity.

    Science.gov (United States)

    Bindesbøll, Christian; Fan, Qiong; Nørgaard, Rikke C; MacPherson, Laura; Ruan, Hai-Bin; Wu, Jing; Pedersen, Thomas Å; Steffensen, Knut R; Yang, Xiaoyong; Matthews, Jason; Mandrup, Susanne; Nebb, Hilde I; Grønning-Wang, Line M

    2015-04-01

    Liver X receptor (LXR)α and LXRβ play key roles in hepatic de novo lipogenesis through their regulation of lipogenic genes, including sterol regulatory element-binding protein (SREBP)-1c and carbohydrate responsive element-binding protein (ChREBP). LXRs activate lipogenic gene transcription in response to feeding, which is believed to be mediated by insulin. We have previously shown that LXRs are targets for glucose-hexosamine-derived O-linked β-N-acetylglucosamine (O-GlcNAc) modification enhancing their ability to regulate SREBP-1c promoter activity in vitro. To elucidate insulin-independent effects of feeding on LXR-mediated lipogenic gene expression in vivo, we subjected control and streptozotocin-treated LXRα/β(+/+) and LXRα/β(-/-) mice to a fasting-refeeding regime. We show that under hyperglycemic and hypoinsulinemic conditions, LXRs maintain their ability to upregulate the expression of glycolytic and lipogenic enzymes, including glucokinase (GK), SREBP-1c, ChREBPα, and the newly identified shorter isoform ChREBPβ. Furthermore, glucose-dependent increases in LXR/retinoid X receptor-regulated luciferase activity driven by the ChREBPα promoter was mediated, at least in part, by O-GlcNAc transferase (OGT) signaling in Huh7 cells. Moreover, we show that LXR and OGT interact and colocalize in the nucleus and that loss of LXRs profoundly reduced nuclear O-GlcNAc signaling and ChREBPα promoter binding activity in vivo. In summary, our study provides evidence that LXRs act as nutrient and glucose metabolic sensors upstream of ChREBP by modulating GK expression, nuclear O-GlcNAc signaling, and ChREBP expression and activity. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  18. Bile acids regulate nuclear receptor (Nur77) expression and intracellular location to control proliferation and apoptosis.

    Science.gov (United States)

    Hu, Ying; Chau, Thinh; Liu, Hui-Xin; Liao, Degui; Keane, Ryan; Nie, Yuqiang; Yang, Hui; Wan, Yu-Jui Yvonne

    2015-02-01

    Bile acids (BA) are endogenous agents capable of causing cancer throughout the gastrointestinal (GI) tract. To uncover the mechanism by which BAs exert carcinogenic effects, both human liver and colon cancer cells as well as mouse primary hepatocytes were treated with BAs and assayed for viability, genotoxic stress, and transcriptional response. BAs induced both Nur77 (NR4A1) and proinflammatory gene expression. The intracellular location of BA-induced Nur77 was time dependent; short-term (1-3 hours) exposure induced nuclear Nur77, whereas longer (1-2 days) exposure also increased cytosolic Nur77 expression and apoptosis. Inhibiting Nur77 nuclear export with leptomycin B decreased lithocholic acid (LCA)-induced apoptosis. Extended (7 days) treatment with BA generated resistance to BA with increased nuclear Nur77, viability, and mobility. While, knockdown of Nur77 in BA-resistant cells increased cellular susceptibility to LCA-induced apoptosis. Moreover, in vivo mouse xenograft experiments demonstrated that BA-resistant cells form larger tumors with elevated Nur77 expression compared with parental controls. DNA-binding and gene expression assays identified multiple survival genes (CDK4, CCND2, MAP4K5, STAT5A, and RBBP8) and a proapoptosis gene (BID) as Nur77 targets. Consistently, BA-induced upregulation of the aforementioned genes was abrogated by a lack of Nur77. Importantly, Nur77 was overexpressed in high percentage of human colon and liver cancer specimens, and the intracellular location of Nur77 correlated with elevated serum total BA levels in patients with colon cancer. These data show for the first time that BAs via Nur77 have a dual role in modulating cell survival and death. These findings establish a direct link between Nur77 and the carcinogenic effect of BAs. ©2014 American Association for Cancer Research.

  19. Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA.

    Science.gov (United States)

    de Vera, Ian Mitchelle S; Zheng, Jie; Novick, Scott; Shang, Jinsai; Hughes, Travis S; Brust, Richard; Munoz-Tello, Paola; Gardner, William J; Marciano, David P; Kong, Xiangming; Griffin, Patrick R; Kojetin, Douglas J

    2017-10-03

    Nuclear receptor (NR) transcription factors bind various coreceptors, small-molecule ligands, DNA response element sequences, and transcriptional coregulator proteins to affect gene transcription. Small-molecule ligands and DNA are known to influence receptor structure, coregulator protein interaction, and function; however, little is known on the mechanism of synergy between ligand and DNA. Using quantitative biochemical, biophysical, and solution structural methods, including 13C-detected nuclear magnetic resonance and hydrogen/deuterium exchange (HDX) mass spectrometry, we show that ligand and DNA cooperatively recruit the intrinsically disordered steroid receptor coactivator-2 (SRC-2/TIF2/GRIP1/NCoA-2) receptor interaction domain to peroxisome proliferator-activated receptor gamma-retinoid X receptor alpha (PPARγ-RXRα) heterodimer and reveal the binding determinants of the complex. Our data reveal a thermodynamic mechanism by which DNA binding propagates a conformational change in PPARγ-RXRα, stabilizes the receptor ligand binding domain dimer interface, and impacts ligand potency and cooperativity in NR coactivator recruitment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Nuclear and chloroplast DNA phylogeography reveals vicariance among European populations of the model species for the study of metal tolerance, Arabidopsis halleri (Brassicaceae).

    Science.gov (United States)

    Pauwels, Maxime; Vekemans, Xavier; Godé, Cécile; Frérot, Hélène; Castric, Vincent; Saumitou-Laprade, Pierre

    2012-03-01

    Arabidopsis halleri is a pseudometallophyte involved in numerous molecular studies of the adaptation to anthropogenic metal stress. In order to test the representativeness of genetic accessions commonly used in these studies, we investigated the A. halleri population genetic structure in Europe. Microsatellite and nucleotide polymorphisms from the nuclear and chloroplast genomes, respectively, were used to genotype 65 populations scattered over Europe. The large-scale population structure was characterized by a significant phylogeographic signal between two major genetic units. The localization of the phylogeographic break was assumed to result from vicariance between large populations isolated in southern and central Europe, on either side of ice sheets covering the Alps during the Quaternary ice ages. Genetic isolation was shown to be maintained in western Europe by the high summits of the Alps, whereas admixture was detected in the Carpathians. Considering the phylogeographic literature, our results suggest a distinct phylogeographic pattern for European species occurring in both mountain and lowland habitats. Considering the evolution of metal adaptation in A. halleri, it appears that recent adaptations to anthropogenic metal stress that have occurred within either phylogeographic unit should be regarded as independent events that potentially have involved the evolution of a variety of genetic mechanisms. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  1. Clinical use of quantitative cardiac perfusion PET: rationale, modalities and possible indications. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM).

    Science.gov (United States)

    Sciagrà, Roberto; Passeri, Alessandro; Bucerius, Jan; Verberne, Hein J; Slart, Riemer H J A; Lindner, Oliver; Gimelli, Alessia; Hyafil, Fabien; Agostini, Denis; Übleis, Christopher; Hacker, Marcus

    2016-07-01

    Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

  2. Performance of cardiac cadmium-zinc-telluride gamma camera imaging in coronary artery disease: a review from the cardiovascular committee of the European Association of Nuclear Medicine (EANM)

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, Denis [CHU Caen and Normandy University, Department of Nuclear Medicine, Caen (France); Normandy University, Caen (France); Marie, Pierre-Yves [University of Lorraine, Faculty of Medicine, Nancyclotep Experimental Imaging Platform, Nancy (France); University of Lorraine, Faculty of Medicine, CHU Nancy, Department of Nuclear Medicine, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); Ben-Haim, Simona [University College London, University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Chaim Sheba Medical Center, Department of Nuclear Medicine, Ramat Gan (Israel); Rouzet, Francois [University Hospital of Paris-Bichat, UMR 1148, Inserm et Paris Diderot-Paris 7 University Paris, Department of Nuclear Medicine, Paris (France); UMR 1148, Inserm and Paris Diderot-Paris 7 University Paris, Paris (France); Songy, Bernard [Centre Cardiologique du Nord, Saint-Denis (France); Giordano, Alessandro [Institute of Nuclear Medicine, Catholic University of Sacred Heart, Largo A. Gemelli, Department of Bioimages and Radiological Sciences, Rome (Italy); Gimelli, Alessia [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Hyafil, Fabien [Bichat University Hospital, Assistance Publique - Hopitaux de Paris, UMR 1148, Inserm and Paris Diderot-Paris 7 University, Department of Nuclear Medicine, Paris (France); Sciagra, Roberto [University of Florence, Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, Florence (Italy); Bucerius, Jan [Maastricht University Medical Center, Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); University Hospital RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany); Verberne, Hein J. [Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands); Slart, Riemer H.J.A. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Twente, Faculty of Science and Technology, Department of Biomedical Photonic Imaging, Enschede (Netherlands); Lindner, Oliver [Institute of Radiology, Nuclear Medicine and Molecular Imaging, Heart and Diabetes Center NRW, Bad Oeynhausen (Germany); Collaboration: Cardiovascular Committee of the European Association of Nuclear Medicine (EANM)

    2016-12-15

    The trade-off between resolution and count sensitivity dominates the performance of standard gamma cameras and dictates the need for relatively high doses of radioactivity of the used radiopharmaceuticals in order to limit image acquisition duration. The introduction of cadmium-zinc-telluride (CZT)-based cameras may overcome some of the limitations against conventional gamma cameras. CZT cameras used for the evaluation of myocardial perfusion have been shown to have a higher count sensitivity compared to conventional single photon emission computed tomography (SPECT) techniques. CZT image quality is further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum likelihood expectation maximization (MLEM), which corrects for the loss in spatial resolution due to line response function of the collimator. All these innovations significantly reduce imaging time and result in a lower patient's radiation exposure compared with standard SPECT. To guide current and possible future users of the CZT technique for myocardial perfusion imaging, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, has decided to examine the current literature regarding procedures and clinical data on CZT cameras. The committee hereby aims (1) to identify the main acquisitions protocols; (2) to evaluate the diagnostic and prognostic value of CZT derived myocardial perfusion, and finally (3) to determine the impact of CZT on radiation exposure. (orig.)

  3. Chloroplast biogenesis-associated nuclear genes: Control by plastid signals evolved prior to their regulation as part of photomorphogenesis.

    Directory of Open Access Journals (Sweden)

    Alison C HIlls

    2015-12-01

    Full Text Available The assembly of photosynthetically-competent chloroplasts occurs in angiosperm seedlings when first exposed to light, and is due to the control by light of photosynthesis-associated nuclear genes (PhANGs, also dependent upon plastid-to-nucleus biogenic communication signals. The relationship between light- and plastid signal-regulation of PhANGs is close but poorly understood. In contrast, many conifers green in the dark and the promoter of a pine PhANG, Lhcb, is active in the dark in tobacco. Here we show that the activity of this promoter in tobacco is sensitive to plastid photobleaching, or to the inhibition of plastid translation in the light or the dark, and the same interventions reduce expression of the native gene in pine seedlings, demonstrating classic plastid biogenic signalling in gymnosperms. Furthermore, Arabidopsis mutations causing defective plastid biogenesis suppress the effect in darkness of mutations in COP1 and DET1, repressors of photomorphogenesis, for the expression of several PhANGs but not a photosynthesis-unrelated, light-regulated gene. GLK transcriptional regulators mediate the response of LHCB but not of other tested PhANGs. We propose gain of the ability by repressors of photomorphogenesis to suppress the response of PhANG promoters to positive plastid biogenic signals in the dark to have contributed to the evolution of light control of chloroplast biogenesis.

  4. Identification and validation of the pathways and functions regulated by the orphan nuclear receptor, ROR alpha1, in skeletal muscle.

    Science.gov (United States)

    Raichur, S; Fitzsimmons, R L; Myers, S A; Pearen, M A; Lau, P; Eriksson, N; Wang, S M; Muscat, G E O

    2010-07-01

    The retinoic acid receptor-related orphan receptor (ROR) alpha has been demonstrated to regulate lipid metabolism. We were interested in the ROR alpha 1 dependent physiological functions in skeletal muscle. This major mass organ accounts for approximately 40% of the total body mass and significant levels of lipid catabolism, glucose disposal and energy expenditure. We utilized the strategy of targeted muscle-specific expression of a truncated (dominant negative) ROR alpha 1 Delta DE in transgenic mice to investigate ROR alpha 1 signaling in this tissue. Expression profiling and pathway analysis indicated that ROR alpha influenced genes involved in: (i) lipid and carbohydrate metabolism, cardiovascular and metabolic disease; (ii) LXR nuclear receptor signaling and (iii) Akt and AMPK signaling. This analysis was validated by quantitative PCR analysis using TaqMan low-density arrays, coupled to statistical analysis (with Empirical Bayes and Benjamini-Hochberg). Moreover, westerns and metabolic profiling were utilized to validate the genes, proteins and pathways (lipogenic, Akt, AMPK and fatty acid oxidation) involved in the regulation of metabolism by ROR alpha 1. The identified genes and pathways were in concordance with the demonstration of hyperglycemia, glucose intolerance, attenuated insulin-stimulated phosphorylation of Akt and impaired glucose uptake in the transgenic heterozygous Tg-ROR alpha 1 Delta DE animals. In conclusion, we propose that ROR alpha 1 is involved in regulating the Akt2-AMPK signaling pathways in the context of lipid homeostasis in skeletal muscle.

  5. G-quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation.

    Science.gov (United States)

    Murat, Pierre; Zhong, Jie; Lekieffre, Lea; Cowieson, Nathan P; Clancy, Jennifer L; Preiss, Thomas; Balasubramanian, Shankar; Khanna, Rajiv; Tellam, Judy

    2014-05-01

    Viruses that establish latent infections have evolved unique mechanisms to avoid host immune recognition. Maintenance proteins of these viruses regulate their synthesis to levels sufficient for maintaining persistent infection but below threshold levels for host immune detection. The mechanisms governing this finely tuned regulation of viral latency are unknown. Here we show that mRNAs encoding gammaherpesviral maintenance proteins contain within their open reading frames clusters of unusual structural elements, G-quadruplexes, which are responsible for the cis-acting regulation of viral mRNA translation. By studying the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1) mRNA, we demonstrate that destabilization of G-quadruplexes using antisense oligonucleotides increases EBNA1 mRNA translation. In contrast, pretreatment with a G-quadruplex-stabilizing small molecule, pyridostatin, decreases EBNA1 synthesis, highlighting the importance of G-quadruplexes within virally encoded transcripts as unique regulatory signals for translational control and immune evasion. Furthermore, these findings suggest alternative therapeutic strategies focused on targeting RNA structure within viral ORFs.

  6. The Plant TPX2 Protein Regulates Prospindle Assembly before Nuclear Envelope Breakdown

    NARCIS (Netherlands)

    Vos, J.W.; Pieuchot, L.; Evrard, J.L.; Janski, N.; Bergdoll, M.; Ronde, de D.

    2008-01-01

    The Targeting Protein for Xklp2 (TPX2) is a central regulator of spindle assembly in vertebrate cells. The absence or excess of TPX2 inhibits spindle formation. We have defined a TPX2 signature motif that is present once in vertebrate sequences but twice in plants. Plant TPX2 is predominantly

  7. Market integration of local energy systems: Is local energy management compatible with European regulation for retail competition?

    NARCIS (Netherlands)

    Eid, C.; Bollinger, L.A.; Koirala, B.P.; Scholten, D.J.; Facchinetti, E.; Lilliestam, J.; Hakvoort, R.A.

    2016-01-01

    The growing penetration of distributed energy resources is opening up opportunities for local energy management (LEM) – the coordination of decentralized energy supply, storage, transport, conversion and consumption within a given geographical area. Because European electricity market liberalization

  8. Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension

    Science.gov (United States)

    Ihalainen, Teemu O.; Aires, Lina; Herzog, Florian A.; Schwartlander, Ruth; Moeller, Jens; Vogel, Viola

    2015-12-01

    Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help decipher how the physical properties of cellular microenvironments regulate nuclear events.

  9. Nuclear safety in countries that are candidate for entry to the European Union; La surete nucleaire dans les pays candidats a l'entree dans l'Union Europeenne

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    In this report, experts from countries members of the European Union have wished to give their collective opinion about nuclear safety in countries that are standing for integrating the E.U.. The investigated countries are Bulgaria, Hungary, Lithuania, Slovakia, Rumania, Slovenia and Czech Republic. This report is based on information given in international cooperation programmes such as Phare programmes as well as in bilateral contacts. 2 aspects are considered: regulatory authorities and the level of safety in operating nuclear power plants. This report does not deal with radioactive waste management nor with radiation protection. (A.C.)

  10. Cross-talk between ROS and calcium in regulation of nuclear activities.

    Science.gov (United States)

    Mazars, Christian; Thuleau, Patrice; Lamotte, Olivier; Bourque, Stéphane

    2010-07-01

    Calcium and Reactive Oxygen Species (ROS) are acknowledged as crucial second messengers involved in the response to various biotic and abiotic stresses. However, it is still not clear how these two compounds can play a role in different signaling pathways leading the plant to a variety of processes such as root development or defense against pathogens. Recently, it has been shown that the concept of calcium and ROS signatures, initially discovered in the cytoplasm, can also be extended to the nucleus of plant cells. In addition, it has been clearly proved that both ROS and calcium signals are intimately interconnected. How this cross-talk can finally modulate the translocation and/or the activity of nuclear proteins leading to the control of specific genes expression is the main focus of this review. We will especially focus on how calcium and ROS interact at the molecular level to modify their targets.

  11. Dark Matter RNA: an Intelligent Scaffold for the Dynamic Regulation of the Nuclear Information Landscape

    Directory of Open Access Journals (Sweden)

    Georges eSt. Laurent

    2012-04-01

    Full Text Available Perhaps no other topic in contemporary genomics has inspired such diverse viewpoints as the 95+% of the genome, previously known as junk DNA, that does not code for proteins. Here, we present a theory in which dark matter RNA plays a role in the generation of a landscape of spatial micro-domains coupled to the information signaling matrix of the nuclear landscape. Within and between these microdomains, dark matter RNAs additionally function to tether RNA interacting proteins and complexes of many different types, and by doing so, allow for a higher performance of the various processes requiring them at ultra-fast rates. This improves signal to noise characteristics of RNA processing, trafficking, and epigenetic signaling, where competition and differential RNA binding among proteins drives the computational decisions inherent in regulatory events.

  12. Dark matter RNA: an intelligent scaffold for the dynamic regulation of the nuclear information landscape

    Science.gov (United States)

    St. Laurent, Georges; Savva, Yiannis A.; Kapranov, Philipp

    2012-01-01

    Perhaps no other topic in contemporary genomics has inspired such diverse viewpoints as the 95+% of the genome, previously known as “junk DNA,” that does not code for proteins. Here, we present a theory in which dark matter RNA plays a role in the generation of a landscape of spatial micro-domains coupled to the information signaling matrix of the nuclear landscape. Within and between these micro-domains, dark matter RNAs additionally function to tether RNA interacting proteins and complexes of many different types, and by doing so, allow for a higher performance of the various processes requiring them at ultra-fast rates. This improves signal to noise characteristics of RNA processing, trafficking, and epigenetic signaling, where competition and differential RNA binding among proteins drives the computational decisions inherent in regulatory events. PMID:22539933

  13. Distinct Structural Features of G Protein-Coupled Receptor Kinase 5 (GRK5) Regulate Its Nuclear Localization and DNA-Binding Ability

    Science.gov (United States)

    Johnson, Laura R.; Robinson, James D.; Lester, Katrina N.; Pitcher, Julie A.

    2013-01-01

    G protein-coupled receptor kinases (GRKs) act to desensitize G protein-coupled receptors (GPCRs). In addition to this role at the plasma membrane, a nuclear function for GRK5, a member of the GRK4 subfamily of GRKs, has been reported. GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5. Here we demonstrate that the possession of a nuclear localization sequence (NLS) is a common feature of GRK4 subfamily members (GRKs 4, 5 and 6). However, the location of the NLS and the ability of these GRKs to bind DNA in vitro are different. The NLSs of GRK5 and 6 bind DNA in vitro, whilst the NLS of GRK4 does not. Using mutants of GRK5 we identify the regions of GRK5 required for DNA-binding in vitro and nuclear localization in cells. The DNA-binding ability of GRK5 requires both the NLS and an N-terminal calmodulin (CaM)-binding site. A functional nuclear export sequence (NES), required for CaM-dependent nuclear export of the kinase, is also identified. Based on our observations we propose a model to explain how nuclear localization of GRK5 may be regulated. Notably, the nuclear localization of GRK5 and 6 is differentially regulated. These results suggest subfamily specific nuclear functions for the GRK4 subfamily members. Identification of GRK specific small molecule inhibitors of nuclear localization and/or function for the GRK4 subfamily may thus be an achievable goal. PMID:23658733

  14. 24th WRSM panel discussion: {open_quotes}The role of research in nuclear regulation: The case of qualified importers{close_quotes}

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, A. [Consejo de Seguridad Nuclear, Madrid (Spain)

    1997-01-01

    Scientific knowledge and technological maturity are needed to establish regulatory requirements, what also needs talent and skills. Scientists are rarely interested in regulation and regulators not always are closely connected to scientific research. This has created gaps in regulations, mainly within qualified importers. A qualified importer, in the sense of this presentation, is a country who has acquired nuclear power plants from more technologically advanced exporters but with an increasing participation of its own industry and institutions in the design, construction, component manufacture and assembly of such nuclear power plants and is fully responsible for the operation of the nuclear units and the corresponding fuel cycle. These countries have also a long standing and independent nuclear regulatory organization and the corresponding technical body. Spain is a qualified importer. In the case of Spain, it originally adopted the codes and regulations of the UE which it was a member of, as well as the codes and standards of the country from which their reactors were produced. Since Spain added KWU plants they even went to German regulations. Plant operation rested with Spain. As problems began to appear in operating plants, local research projects were funded to study the problems, aimed at immediate solutions, but also providing training for local personnel in addition to information of use for regulators. Spain has participated in many joint research projects, which have trained people, and given confidence to Spaniards involved in science and regulations. Qualified importers, like Spain, participate in research, even though it may not translate itself into regulation. Such participation will always serve to give self-confidence and independence to regulators and licensees, to better understand the adopted regulations of the most advanced countries and to solve specific problems.

  15. Regulation of CYP3A4 by pregnane X receptor: The role of nuclear receptors competing for response element binding

    Energy Technology Data Exchange (ETDEWEB)

    Istrate, Monica A., E-mail: monicai@scripps.edu [Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany, and University of Tuebingen, Auerbachstr. 112, D-70376 Stuttgart (Germany); Nussler, Andreas K., E-mail: nuessler@uchir.me.tum.de [Department of Traumatology, Technical University Munich, Ismaningerstr. 22, 81675 Munich (Germany); Eichelbaum, Michel, E-mail: michel.eichelbaum@ikp-stuttgart.de [Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany, and University of Tuebingen, Auerbachstr. 112, D-70376 Stuttgart (Germany); Burk, Oliver, E-mail: oliver.burk@ikp-stuttgart.de [Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany, and University of Tuebingen, Auerbachstr. 112, D-70376 Stuttgart (Germany)

    2010-03-19

    Induction of the major drug metabolizing enzyme CYP3A4 by xenobiotics contributes to the pronounced interindividual variability of its expression and often results in clinically relevant drug-drug interactions. It is mainly mediated by PXR, which regulates CYP3A4 expression by binding to several specific elements in the 5' upstream regulatory region of the gene. Induction itself shows a marked interindividual variability, whose underlying determinants are only partly understood. In this study, we investigated the role of nuclear receptor binding to PXR response elements in CYP3A4, as a potential non-genetic mechanism contributing to interindividual variability of induction. By in vitro DNA binding experiments, we showed that several nuclear receptors bind efficiently to the proximal promoter ER6 and distal xenobiotic-responsive enhancer module DR3 motifs. TR{alpha}1, TR{beta}1, COUP-TFI, and COUP-TFII further demonstrated dose-dependent repression of PXR-mediated CYP3A4 enhancer/promoter reporter activity in transient transfection in the presence and absence of the PXR inducer rifampin, while VDR showed this effect only in the absence of treatment. By combining functional in vitro characterization with hepatic expression analysis, we predict that TR{alpha}1, TR{beta}1, COUP-TFI, and COUP-TFII show a strong potential for the repression of PXR-mediated activation of CYP3A4 in vivo. In summary, our results demonstrate that nuclear receptor binding to PXR response elements interferes with PXR-mediated expression and induction of CYP3A4 and thereby contributes to the interindividual variability of induction.

  16. Histone demethylase Jumonji D3 (JMJD3 as a tumor suppressor by regulating p53 protein nuclear stabilization.

    Directory of Open Access Journals (Sweden)

    Chibawanye I Ene

    Full Text Available Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3 resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs, where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation and chromatin independent (nuclear p53 protein stabilization mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.

  17. Homotypic cell cannibalism, a cell-death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer

    Science.gov (United States)

    Cano, Carla E; Sandí, María José; Hamidi, Tewfik; Calvo, Ezequiel L; Turrini, Olivier; Bartholin, Laurent; Loncle, Céline; Secq, Véronique; Garcia, Stéphane; Lomberk, Gwen; Kroemer, Guido; Urrutia, Raul; Iovanna, Juan L

    2012-01-01

    Pancreatic adenocarcinoma (PDAC) is an extremely deadly disease for which all treatments available have failed to improve life expectancy significantly. This may be explained by the high metastatic potential of PDAC cells, which results from their dedifferentiation towards a mesenchymal phenotype. Some PDAC present cell-in-cell structures whose origin and significance are currently unknown. We show here that cell-in-cells form after homotypic cell cannibalism (HoCC). We found PDAC patients whose tumours display HoCC develop less metastasis than those without. In vitro, HoCC was promoted by inactivation of the nuclear protein 1 (Nupr1), and was enhanced by treatment with transforming growth factor β. HoCC ends with death of PDAC cells, consistent with a metastasis suppressor role for this phenomenon. Hence, our data indicates a protective role for HoCC in PDAC and identifies Nupr1 as a molecular regulator of this process. PMID:22821859

  18. Food Components Modulate Obesity and Energy Metabolism via the Transcriptional Regulation of Lipid-Sensing Nuclear Receptors.

    Science.gov (United States)

    Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo

    2015-01-01

    Obesity is a major risk factor for chronic diseases such as diabetes, cardiovascular diseases, and hypertension. Many modern people have a tendency to overeat owing to stress and loosening of self-control. Moreover, energy expenditure varies greatly among individuals. Scientific reduction of obesity is important under these circumstances. Furthermore, recent research on molecular levels has clarified the differentiation of adipocytes, the level of subsequent fat accumulation, and the secretion of the biologically active adipokines by adipocytes. Adipose tissues and obesity have become the most important target for the prevention and treatment of many chronic diseases. We have identified various food-derived compounds modulating nuclear receptors, especially peroxisome proliferators-activated receptor(PPAR), in the regulation of energy metabolism and obesity. In this review, we discuss the PPARs that are most important in obesity and energy metabolism.

  19. Transfection of chicken cerebellar granule neurons used to study glucocorticoid receptor regulation by nuclear receptor 4A (NR4A).

    Science.gov (United States)

    Strøm, Bjørn O; Aden, Petra; Mathisen, Gro H; Lømo, Jon; Davanger, Svend; Paulsen, Ragnhild E

    2010-10-30

    Transfection is a useful tool for studying molecular signalling pathways. However, neurons have proven hard to transfect. In the present paper we have optimized a new electroporation procedure using the Cellaxess(®) system for transient transfection of adherent primary neurons from chicken (Gallus gallus) and compared it to a liposome based procedure using Metafectene(®) Pro. In order to evaluate the two methods, glucocorticoid receptor (GR) function was chosen as a test. GRs are expressed in high amounts in the cerebellum. GR is regulated by another nuclear receptor (NGFI-B, the first member found in the NR4A family). We first showed that forskolin and phorbol ester activated an NR4A-dependent reporter gene indicating that members of the NR4A nuclear receptor family are present endogenously and upregulated by external stimuli. Then, transfected NGFI-B was shown to antagonize the dexamethasone-activated transcriptional activation by endogenous GR, leading to the conclusion that NR4A-family members are important modulators of GR mediated regulatory processes in the cerebellum, as in other cell types. Both transfection methods proved useful. While the electroporation technique yielded small rings with many transfected cells optimal for microscopy studies, the liposome based method resulted in transfected cells evenly distributed in the dish rendering this method well suited for biochemical studies. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. The function of nuclear receptors in regulation of female reproduction and embryogenesis in the red flour beetle, Tribolium castaneum.

    Science.gov (United States)

    Xu, Jingjing; Tan, Anjiang; Palli, Subba R

    2010-10-01

    Nineteen canonical and two Knirps-like family nuclear receptors (NRs) were identified in the genome of Tribolium castaneum. The current study was conducted to determine the function of these NRs in regulation of female reproduction and embryogenesis. RNA interference (RNAi)-aided knock-down in the expression of genes coding for 21 NRs showed that seven NRs E75, hormone receptor 3 (HR3), ecdysone receptor (EcR), ultraspiracle (USP), seven-up (SVP), FTZ transcription factor 1 (FTZ-F1) and hormone receptor 4 (HR4) are required for successful vitellogenesis and oogenesis. Knocking down the expression of genes coding for these seven NRs affected egg production by reducing the levels of vitellogenin mRNAs as well as by affecting the oocyte maturation. Expression of seven additional NRs hormone receptor 96 (HR96), hormone receptor 51 (HR51), hormone receptor 38 (HR38), hormone receptor 39 (HR39), Tailless (Tll), Dissatisfaction (Dsf) and Knirps-like is required for successful embryogenesis. The knock-down in the expression of genes coding for three other NRs (E78, hepatocyte nuclear factor 4, HNF4 and Eagle) partially blocked embryogenesis. This study showed that at least 17 out of the 21 NRs identified in T. castaneum play key roles in female reproduction and embryogenesis. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Regulation of miR-200c by nuclear receptors PPAR{alpha}, LRH-1 and SHP

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuxia; Yang, Zhihong [Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Department of Oncological Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Whitby, Richard [Department of Chemistry, University of Southampton, Southampton, Hants SO17 1BJ (United Kingdom); Wang, Li, E-mail: l.wang@hsc.utah.edu [Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Department of Oncological Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Knockdown of PPAR{alpha} and LRH-1 abolishes miR-200c inhibition of HCC cell migration. Black-Right-Pointing-Pointer SHP represses miR-200c expression via inhibition of the activity of PPAR{alpha} and LRH-1. Black-Right-Pointing-Pointer RJW100 exhibits strong ability to downregulate ZEB1 and ZEB2 proteins. -- Abstract: We investigated regulation of miR-200c expression by nuclear receptors. Ectopic expression of miR-200c inhibited MHCC97H cell migration, which was abrogated by the synergistic effects of PPAR{alpha} and LRH-1 siRNAs. The expression of miR-200c was decreased by PPAR{alpha}/LRH-1 siRNAs and increased by SHP siRNAs, and overexpression of the receptors reversed the effects of their respective siRNAs. SHP siRNAs also drastically enhanced the ability of the LRH-1 agonist RJW100 to induce miR-200c and downregulate ZEB1 and ZEB2 proteins. Co-expression of PPAR{alpha} and LRH-1 moderately transactivated the miR-200c promoter, which was repressed by SHP co-expression. RJW100 caused strong activation of the miR-200c promoter. This is the first report to demonstrate that miR-200c expression is controlled by nuclear receptors.

  2. Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease.

    Science.gov (United States)

    Chemmannur, S V; Badhwar, A J; Mirlekar, B; Malonia, S K; Gupta, M; Wadhwa, N; Bopanna, R; Mabalirajan, U; Majumdar, S; Ghosh, B; Chattopadhyay, S

    2015-11-01

    Asthma is a complex airway allergic disease involving the interplay of various cell types, cytokines, and transcriptional factors. Though many factors contribute to disease etiology, the molecular control of disease phenotype and responsiveness is not well understood. Here we report an essential role of the matrix attachment region (MAR)-binding protein SMAR1 in regulating immune response during allergic airway disease. Conditional knockout of SMAR1 in T cells rendered the mice resistant to eosinophilic airway inflammation against ovalbumin (OVA) allergen with low immunoglobulin E (IgE) and interleukin-5 (IL-5) levels. Moreover, a lower IgE/IgG2a ratio and higher interferon-γ (IFN-γ) response suggested aberrant skewing of T-cell differentiation toward type 1 helper T cell (Th1) response. We show that SMAR1 functions as a negative regulator of Th1 and Th17 differentiation by interacting with two potential and similar MAR regions present on the promoters of T-bet and IL-17. Thus, we present SMAR1 as a regulator of T-cell differentiation that favors the establishment of Th2 cells by modulating Th1 and Th17 responses.

  3. Model Checking for Licensing Support in the Finnish Nuclear Industry

    Energy Technology Data Exchange (ETDEWEB)

    Antti, Pakonen; Janne, Valkonen [VTT Technical Research, VTT (Finland); Sami, Matinaho; Markus, Hartikainen [Protum Power and Heat, Fortum (Finland)

    2014-08-15

    This paper examines how model checking can be used to support the qualification of digital I and C software in nuclear power plants, in a way that is consistent with regulatory demands specifically, the common position of seven European nuclear regulators and authorised technical support organisations. As a practical example, we discuss the third-party review service provided by VTT for the power company Fortum in the I and C renewal project of the Loviisa plant in southern Finland.

  4. Global regulation of international intellectual property through Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS: The European Union and Brazil

    Directory of Open Access Journals (Sweden)

    Delphine Aurélie Laurence Defossez

    2017-10-01

    Full Text Available Purpose – This paper focuses on the regulation of copyrights at international level by comparing the situation under the TRIPS agreement in Brazil and in the European Union. Methodology/approach/design – This article analyses standards and literature on regulation, as well as the role of TRIPS agreement. Attention was specially drawn to the market failure theory for justifying regulation, advocated by Baldwin & Cave. The TRIPS agreement will be analysed through Baldwin’s five criteria for good regulation. Findings – The TRIPS agreement substantially widened the scope of governance of copyrights but imposes the WTO view on the matter. Notwithstanding its flaws, the TRIPS agreement remains the most comprehensive international agreement on intellectual property. According to Baldwin’s theory, the TRIPS agreement as a regulation is a good regulation. Indeed, it achieves the major part of the goals it set. However, some of the declared goals have never come to existence and had been replaced by other goals. On the overall, the TRIPS agreement has the capacity to regulate international intellectual property. Originality/value – This paper analyses the TRIPS agreement as a way forward in the harmonization of the rules on intellectual property.

  5. Towards a future with large penetration of distributed generation: Is the current regulation of electricity distribution ready? Regulatory recommendations under a European perspective

    Energy Technology Data Exchange (ETDEWEB)

    Cossent, Rafael [Instituto de Investigacion Tecnologica, Escuela Tecnica Superior de Ingenieria, Universidad Pontificia Comillas, C/ Quintana 21, 28008 Madrid (Spain)], E-mail: Rafael.Cossent@iit.upcomillas.es; Gomez, Tomas; Frias, Pablo [Instituto de Investigacion Tecnologica, Escuela Tecnica Superior de Ingenieria, Universidad Pontificia Comillas, C/ Quintana 21, 28008 Madrid (Spain)

    2009-03-15

    The European Energy Policy promotes renewable energy sources and energy efficiency as means to mitigate environmental impact, increase security of supply and ensure economic competitiveness. As a result, the penetration levels of distributed generation (DG) in electricity networks are bound to increase. Distribution networks and distribution system operators (DSOs) will be especially affected by growing levels of DG. This paper reviews the current regulation of distribution in the European Union Member States, focusing on those aspects that might hinder the future integration of DG. Several regulatory issues that may hinder a successful integration of DG have been identified. Recommendations to improve the current situation are proposed. Regarding economic signals sent to DG, connection charges and cost-reflective use-of-system charges together with incentives to provide ancillary services are the key aspects. Concerning DSOs regulation, unbundling from generation and supply according to the European Electricity Directive, incentives for optimal planning and network operation considering DG, including energy losses and quality of service, and innovation schemes to migrate to active networks are the most relevant topics.

  6. Towards a future with large penetration of distributed generation. Is the current regulation of electricity distribution ready? Regulatory recommendations under a European perspective

    Energy Technology Data Exchange (ETDEWEB)

    Cossent, Rafael; Gomez, Tomas; Frias, Pablo [Instituto de Investigacion Tecnologica, Escuela Tecnica Superior de Ingenieria, Universidad Pontificia Comillas, C/ Quintana 21, 28008 Madrid (Spain)

    2009-03-15

    The European Energy Policy promotes renewable energy sources and energy efficiency as means to mitigate environmental impact, increase security of supply and ensure economic competitiveness. As a result, the penetration levels of distributed generation (DG) in electricity networks are bound to increase. Distribution networks and distribution system operators (DSOs) will be especially affected by growing levels of DG. This paper reviews the current regulation of distribution in the European Union Member States, focusing on those aspects that might hinder the future integration of DG. Several regulatory issues that may hinder a successful integration of DG have been identified. Recommendations to improve the current situation are proposed. Regarding economic signals sent to DG, connection charges and cost-reflective use-of-system charges together with incentives to provide ancillary services are the key aspects. Concerning DSOs regulation, unbundling from generation and supply according to the European Electricity Directive, incentives for optimal planning and network operation considering DG, including energy losses and quality of service, and innovation schemes to migrate to active networks are the most relevant topics. (author)

  7. Legislative and non-legislative regulations concerning Rx drug advertisement in the European Union and the United States--comparative analysis.

    Science.gov (United States)

    Czerw, Aleksandra; Religioni, Urszula

    2012-01-01

    Drug advertising is one of the most popular forms of communication between pharmaceutical companies and prospect drug purchasers. In the face of strong competition on the pharmaceutical market on the one hand, and patient's high susceptibility to various forms of advertising on the other, drug producers try to reach as wide group of recipients as possible. However, proper medicine use requires not only doctor's wide knowledge and experience, but also patient's awareness of necessity of rational drug usage. Advertising activities related to this group of medicines are covered by rigorous law regulations, with taking into account above-mentioned issues, and other specific features of drugs available with prescription. The aim of this article is to present legislative and non-legislative regulations concerning Rx drugs, taking into consideration law regulations that are in force in the European Union and the United States. Ethic codes implemented by drug producers associations were also used.

  8. Nuclear receptor co-repressor SMRT regulates mitochondrial oxidative metabolism and mediates aging related metabolic deterioration

    Science.gov (United States)

    Reilly, Shannon M.; Bhargava, Prerna; Liu, Sihao; Gangl, Matthew R.; Gorgun, Cem; Nofsinger, Russell R.; Evans, Ronald M.; Qi, Lu; Hu, Frank B.; Lee, Chih-Hao

    2010-01-01

    Summary The transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification. The physiological significance of such interaction remains unclear. We find SMRT expression and its occupancy on peroxisome proliferator-activated receptor (PPAR) target gene promoters are increased with age in major metabolic tissues. Genetic manipulations to selectively disable RID1 (SMRTmRID1) demonstrate that shifting SMRT repression to RID2-associated NRs, notably PPARs, causes premature aging and related metabolic diseases accompanied by reduced mitochondrial function and anti-oxidant gene expression. SMRTmRID1 cells exhibit increased susceptibility to oxidative damage, which could be rescued by PPAR activation or anti-oxidant treatment. In concert, several human SMRT gene polymorphisms are found to nominally associate with type 2 diabetes and adiponectin levels. These data uncover a role for SMRT in mitochondrial oxidative metabolism and the aging process, which may serve as a drug target to improve health span. PMID:21109196

  9. Nuclear receptor corepressor SMRT regulates mitochondrial oxidative metabolism and mediates aging-related metabolic deterioration.

    Science.gov (United States)

    Reilly, Shannon M; Bhargava, Prerna; Liu, Sihao; Gangl, Matthew R; Gorgun, Cem; Nofsinger, Russell R; Evans, Ronald M; Qi, Lu; Hu, Frank B; Lee, Chih-Hao

    2010-12-01

    The transcriptional corepressor SMRT utilizes two major receptor-interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification. The physiological significance of such interaction remains unclear. We find SMRT expression and its occupancy on peroxisome proliferator-activated receptor (PPAR) target gene promoters are increased with age in major metabolic tissues. Genetic manipulations to selectively disable RID1 (SMRT(mRID1)) demonstrate that shifting SMRT repression to RID2-associated NRs, notably PPARs, causes premature aging and related metabolic diseases accompanied by reduced mitochondrial function and antioxidant gene expression. SMRT(mRID1) cells exhibit increased susceptibility to oxidative damage, which could be rescued by PPAR activation or antioxidant treatment. In concert, several human Smrt gene polymorphisms are found to nominally associate with type 2 diabetes and adiponectin levels. These data uncover a role for SMRT in mitochondrial oxidative metabolism and the aging process, which may serve as a drug target to improve health span. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. The functionally elusive RabI chromosome configuration directly regulates nuclear membrane remodeling at mitotic onset.

    Science.gov (United States)

    Fernández-Álvarez, Alfonso; Cooper, Julia Promisel

    2017-08-03

    Despite its ubiquity in interphase eukaryotic nuclei, the functional significance of the RabI configuration, in which interphase centromeres are clustered at the nuclear envelope (NE) near the centrosome and telomeres localize at the opposite end of the nucleus, has remained mysterious. In a broad variety of organisms, including Schizosaccharomyces pombe, the RabI configuration is maintained throughout mitotic interphase. The fission yeast linker of nucleoskeleton and cytoskeleton (LINC) complex mediates this centromere association. The functional significance of centromere positioning during interphase has been recently revealed using a conditionally inactivated LINC allele that maintains LINC stability but releases interphase centromere-LINC contacts. Remarkably, this interphase release abolishes mitotic spindle formation. Here, we confirm these observations using an alternative strategy to explore the role of centromere-NE association without modifying the LINC complex. We analyze spindle dynamics in cells lacking Csi1, a stabilizer of centromere-LINC associations, and Lem2, a NE protein harboring lamin interacting domains. We recapitulate these observations and their implications for the functional significance of centromere positioning for cell cycle progression in fission yeast and most likely, a wide range of eukaryotes.

  11. The nuclear receptor REV-ERBα regulates Fabp7 and modulates adult hippocampal neurogenesis.

    Directory of Open Access Journals (Sweden)

    Anna Schnell

    Full Text Available The function of the nuclear receptor Rev-erbα (Nr1d1 in the brain is, apart from its role in the circadian clock mechanism, unknown. Therefore, we compared gene expression profiles in the brain between wild-type and Rev-erbα knock-out (KO animals. We identified fatty acid binding protein 7 (Fabp7, Blbp as a direct target of repression by REV-ERBα. Loss of Rev-erbα manifested in memory and mood related behavioral phenotypes and led to overexpression of Fabp7 in various brain areas including the subgranular zone (SGZ of the hippocampus, where neuronal progenitor cells (NPCs can initiate adult neurogenesis. We found increased proliferation of hippocampal neurons and loss of its diurnal pattern in Rev-erbα KO mice. In vitro, proliferation and migration of glioblastoma cells were affected by manipulating either Fabp7 expression or REV-ERBα activity. These results suggest an important role of Rev-erbα and Fabp7 in adult neurogenesis, which may open new avenues for treatment of gliomas as well as neurological diseases such as depression and Alzheimer.

  12. The role of research in nuclear regulation: A US industry perspective

    Energy Technology Data Exchange (ETDEWEB)

    Simard, R.L.

    1997-01-01

    The author reviews the focus of research efforts within the NRC following the development of nuclear energy. Initial work focused on research in support of rulemaking and generic-issue resolution largely to support the licensing of U.S. plants that was going on at the time, including study of design basis accidents. Going into the 1980`s there was a need for information on accidents beyond the design basis, following the TMI accident. Aging research became relevant with the plants accumulating years of operation. More recently effort has gone into work on more advanced reactor designs. Looking ahead the author argues there may be few unresolved safety issues, and analytic tools are presently very well developed. So the question of what to do in the future is relevant, especially when coupled with changing responsibilities, changing legislation, changing budgets, changing market forces, and changing expectations from consumers. So the author poses questions which should be addressed as one looks at planning for the role of research in the NRC in the future.

  13. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bolo, N.R.

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. {sup 13}C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of ({sup 13}C-4) to ({sup 13}C-5)-glutamate, ({sup 13}C-3) to ({sup 13}C-2)-alanine or ({sup 13}C-3) to ({sup 13}C-2)-lactate produced when ({sup 13}C-2)-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the {sup 13}C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in {sup 13}C NMR human studies from the current literature.

  14. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yue; Hu, Yali; Zhao, Jing; Zhen, Xin [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Yan, Guijun, E-mail: yanguijun33@gmail.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Sun, Haixiang, E-mail: stevensunz@163.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)

    2011-01-14

    Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

  15. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    Energy Technology Data Exchange (ETDEWEB)

    Knipe, David M., E-mail: david_knipe@hms.harvard.edu

    2015-05-15

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression.

  16. Emotion reactivity and regulation are associated with psychological functioning following the 2011 earthquake, tsunami, and nuclear crisis in Japan.

    Science.gov (United States)

    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.

  17. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle.

    Science.gov (United States)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-08-15

    The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Proposal of guidelines for structuring an independent regulation body for the Brazilian nuclear sector; Proposta de diretrizes para estruturacao de um orgao de regulacao independente para o setor nuclear brasileiro

    Energy Technology Data Exchange (ETDEWEB)

    Nicoll Junior, Ricardo

    2016-07-01

    Regulatory bodies are responsible for regulation in various sectors of society. In Brazil, they work in various areas for the development of the country and have as main objective the social, economic and national development. The progress of new technologies in the nuclear field and their commercialization underscores the need for regulation according to international safety standards. The present research searches through an extensive review of the literature identify the international guidelines for regulatory bodies and make a comparative analysis between Brazil and five countries that have independent regulatory bodies in the nuclear sector. The purpose of the work is to contribute to the Brazilian public sectors, with an evaluation of the country's regulation in the perception of specialists and propose guidelines for the structuring of an independent regulatory body, respecting international agreements and the legislation in force in the country. (author)

  19. Nuclear networking.

    Science.gov (United States)

    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.

  20. Nuclear domain 10 components upregulated via interferon during human cytomegalovirus infection potently regulate viral infection.

    Science.gov (United States)

    Ashley, Caroline L; Glass, Mandy S; Abendroth, Allison; McSharry, Brian P; Slobedman, Barry

    2017-07-01

    Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection. In this study, analysis of ND10 component transcription during HCMV infection demonstrated that PML and Sp100 were significantly upregulated whilst hDaxx expression remained unchanged. In cells engineered to block the production of, or response to, type I IFNs, upregulation of PML and Sp100 was not detected during HCMV infection. Furthermore, pre-treatment with an IFN-β neutralizing antibody inhibited upregulation of PML and Sp100 during both infection and treatment with HCMV-infected cell supernatant. The significance of ND10 components functioning as anti-viral ISGs during HCMV infection was determined through knockdown of PML, Sp100 and hDaxx. ND10 knockdown cells were significantly more permissive to HCMV infection, as previously described but, in contrast to control cells, could support HCMV plaque formation following IFN-β pre-treatment. This ability of HCMV to overcome the potently anti-viral effects of IFN-β in ND10 expression deficient cells provides evidence that ND10 component upregulation is a key mediator of the anti-viral activity of IFN-β.

  1. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bolo, Nicolas Robin [Univ. of California, Berkeley, CA (United States)

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. 13C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of [13C-4] to [13C-5]-glutamate, [13C-3] to [13C-2]-alanine or [13C-3] to [13C-2]-lactate produced when [13C-2]-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the 13C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in 13C NMR human studies from the current literature.

  2. Hepatocyte Nuclear Factor 4α Controls Iron Metabolism and Regulates Transferrin Receptor 2 in Mouse Liver*

    Science.gov (United States)

    Matsuo, Shunsuke; Ogawa, Masayuki; Muckenthaler, Martina U.; Mizui, Yumiko; Sasaki, Shota; Fujimura, Takafumi; Takizawa, Masayuki; Ariga, Nagayuki; Ozaki, Hiroaki; Sakaguchi, Masakiyo; Gonzalez, Frank J.; Inoue, Yusuke

    2015-01-01

    Iron is an essential element in biological systems, but excess iron promotes the formation of reactive oxygen species, resulting in cellular toxicity. Several iron-related genes are highly expressed in the liver, a tissue in which hepatocyte nuclear factor 4α (HNF4α) plays a critical role in controlling gene expression. Therefore, the role of hepatic HNF4α in iron homeostasis was examined using liver-specific HNF4α-null mice (Hnf4aΔH mice). Hnf4aΔH mice exhibit hypoferremia and a significant change in hepatic gene expression. Notably, the expression of transferrin receptor 2 (Tfr2) mRNA was markedly decreased in Hnf4aΔH mice. Promoter analysis of the Tfr2 gene showed that the basal promoter was located at a GC-rich region upstream of the transcription start site, a region that can be transactivated in an HNF4α-independent manner. HNF4α-dependent expression of Tfr2 was mediated by a proximal promoter containing two HNF4α-binding sites located between the transcription start site and the translation start site. Both the GC-rich region of the basal promoter and the HNF4α-binding sites were required for maximal transactivation. Moreover, siRNA knockdown of HNF4α suppressed TFR2 expression in human HCC cells. These results suggest that Tfr2 is a novel target gene for HNF4α, and hepatic HNF4α plays a critical role in iron homeostasis. PMID:26527688

  3. Hepatocyte Nuclear Factor 4α Controls Iron Metabolism and Regulates Transferrin Receptor 2 in Mouse Liver.

    Science.gov (United States)

    Matsuo, Shunsuke; Ogawa, Masayuki; Muckenthaler, Martina U; Mizui, Yumiko; Sasaki, Shota; Fujimura, Takafumi; Takizawa, Masayuki; Ariga, Nagayuki; Ozaki, Hiroaki; Sakaguchi, Masakiyo; Gonzalez, Frank J; Inoue, Yusuke

    2015-12-25

    Iron is an essential element in biological systems, but excess iron promotes the formation of reactive oxygen species, resulting in cellular toxicity. Several iron-related genes are highly expressed in the liver, a tissue in which hepatocyte nuclear factor 4α (HNF4α) plays a critical role in controlling gene expression. Therefore, the role of hepatic HNF4α in iron homeostasis was examined using liver-specific HNF4α-null mice (Hnf4a(ΔH) mice). Hnf4a(ΔH) mice exhibit hypoferremia and a significant change in hepatic gene expression. Notably, the expression of transferrin receptor 2 (Tfr2) mRNA was markedly decreased in Hnf4a(ΔH) mice. Promoter analysis of the Tfr2 gene showed that the basal promoter was located at a GC-rich region upstream of the transcription start site, a region that can be transactivated in an HNF4α-independent manner. HNF4α-dependent expression of Tfr2 was mediated by a proximal promoter containing two HNF4α-binding sites located between the transcription start site and the translation start site. Both the GC-rich region of the basal promoter and the HNF4α-binding sites were required for maximal transactivation. Moreover, siRNA knockdown of HNF4α suppressed TFR2 expression in human HCC cells. These results suggest that Tfr2 is a novel target gene for HNF4α, and hepatic HNF4α plays a critical role in iron homeostasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. The nuclear retinoid-related orphan receptor-α regulates adipose tissue glyceroneogenesis in addition to hepatic gluconeogenesis.

    Science.gov (United States)

    Kadiri, Sarah; Monnier, Chloé; Ganbold, Munkhzul; Ledent, Tatiana; Capeau, Jacqueline; Antoine, Bénédicte

    2015-07-15

    Circadian rhythms have an essential role in feeding behavior and metabolism. RORα is a nuclear receptor involved in the interface of the circadian system and metabolism. The adipocyte glyceroneogenesis pathway derives free fatty acids (FFA) liberated by lipolysis to reesterification into triglycerides, thus regulating FFA homeostasis and fat mass. Glyceroneogenesis shares with hepatic gluconeogenesis the key enzyme phosphoenolpyruvate carboxykinase c (PEPCKc), whose gene is a RORα target in the liver. RORα-deficient mice (staggerer, ROR(sg/sg)) have been shown to exhibit a lean phenotype and fasting hypoglycemia for unsolved reasons. In the present study, we investigated whether adipocyte glyceroneogenesis might also be a target pathway of RORα, and we further evaluated the role of RORα in hepatocyte gluconeogenesis. In vivo investigations comparing ROR(sg/sg) mice with their wild-type (WT) littermates under fasting conditions demonstrated that, in the absence of RORα, the release of FFA into the bloodstream was altered and the rise in glycemia in response to pyruvate reduced. The functional analysis of each pathway, performed in adipose tissue or liver explants, confirmed the impairment of adipocyte glyceroneogenesis and liver gluconeogenesis in the ROR(sg/sg) mice; these reductions of FFA reesterification or glucose production were associated with decreases in PEPCKc mRNA and protein levels. Treatment of explants with RORα agonist or antagonist enhanced or inhibited these pathways, respectively, in tissues isolated from WT but not ROR(sg/sg) mice. Our results indicated that both adipocyte glyceroneogenesis and hepatocyte gluconeogenesis were regulated by RORα. This study demonstrates the physiological function of RORα in regulating both glucose and FFA homeostasis. Copyright © 2015 the American Physiological Society.

  5. Which lessons can we learn from the European Union legal framework of medicines for the regulation of direct-to-consumer genetic tests?

    Science.gov (United States)

    van Hellemondt, Rachèl; Hendriks, Aart; Breuning, Martijn

    2012-01-01

    The legal framework of the European Union (EU) for regulating access to and supply of direct-to-consumer (DTC) genetic tests is very liberal compared to the legal and regulatory framework for (internet) medicines. Nevertheless, both health related products can cause equally serious damage to the well being of individuals. In this contribution we examine whether the legal framework of the EU for the safety and responsible use of (internet) medicines could be an example for regulating access to and supply of DTC genetic tests. The EU laws governing medicines can, notwithstanding their shortcomings, serve as an example for (central) authorising the marketing of DTC genetic tests on the internal market in accordance with strict criteria regarding predictive value and clinical usefulness. Furthermore, a legal framework controlling DTC genetic tests also should introduce system supervision as well as quality criteria with respect to the information to be provided to consumers in order to enhance health protection. However, DTC genetic tests purchased through online ordering are difficult to supervise by any agency. Adequately protecting individuals against questionable testing kits calls for international vigilance and comprehensive measures by the international community. For Europe, it is important to rank the regulation of DTC genetic tests on the European regulatory agenda.

  6. Radiation protection in odontology: French regulation and new European standards; La radioprotection en odontologie: reglementation francaise et nouvelles normes europeennes

    Energy Technology Data Exchange (ETDEWEB)

    Foucart, J.M

    2004-07-01

    This a point on the regulatory evolutions in the field of radiation protection in the daily practice of odontology, consecutive to the transposition in French law of European directives. This work proposes practical cards to manage installation in radiodiagnosis in order to protect professional personnel and patients. (N.C.)

  7. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

    DEFF Research Database (Denmark)

    Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb

    2016-01-01

    Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with c...

  8. Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α

    Energy Technology Data Exchange (ETDEWEB)

    Theofilatos, Dimitris; Anestis, Aristomenis [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, 71003, Crete (Greece); Hashimoto, Koshi [Department of Preemptive Medicine and Metabolism, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-city, Tokyo, 113-8510 (Japan); Kardassis, Dimitris, E-mail: kardasis@imbb.forth.gr [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, 71003, Crete (Greece)

    2016-01-15

    Liver X Receptors (LXRs) are sterol-activated transcription factors that play major roles in cellular cholesterol homeostasis, HDL biogenesis and reverse cholesterol transport. The aim of the present study was to investigate the mechanisms that control the expression of the human LXRα gene in hepatic cells. A series of reporter plasmids containing consecutive 5′ deletions of the hLXRα promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the human LXRα promoter was significantly reduced by deleting the −111 to −42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 α (HNF-4α) in this area. Overexpression of HNF-4α in HEK 293T cells increased the expression of all LXRα promoter constructs except −42/+384. In line, silencing the expression of endogenous HNF-4α in HepG2 cells was associated with reduced LXRα protein levels and reduced activity of the −111/+384 LXRα promoter but not of the −42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel HNF-4α specific binding motif (H4-SBM) in the −50 to −40 region of the human LXRα promoter. A triple mutation in this H4-SBM abolished HNF-4α binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by HNF-4α. In conclusion, our data indicate that HNF-4α may have a wider role in cell and plasma cholesterol homeostasis by controlling the expression of LXRα in hepatic cells. - Highlights: • The human LXRα promoter contains a HNF-4α specific binding motif in the proximal −50/−40 region. • Mutations in this motif abolished HNF4α binding and transactivation of the h

  9. [Effects of temperature and light variations, and of radiothyroidectomy on body weight regulation in the European hamster (Cricetus cricetus) (author's transl)].

    Science.gov (United States)

    Canguilhem, B; Koch, A

    1976-09-01

    Regain of body weight in European Hamsters after fasting was investigated at various periods of the year and under different ambient conditions (fig. 1) with and without radiothyroidectomy. 1. Weight gain after food deprivation proceeds at rates which vary with the season. It is faster in spring and summer than in winter. 2. Variations in ambient temperature and in light conditions do not influence the daily weight gain and the relative rate of weight increase (fig. 2,3). 3. Radiothroidectomy depresses these two parameters in winter as well as in spring, and lowers the level of the set point of the regulating mechanism (fig. 4,5).

  10. ESTABLISHING FINAL END STATE FOR A RETIRED NUCLEAR WEAPONS PRODUCTION REACTOR; COLLABORATION BETWEEN STAKEHOLDERS, REGULATORS, AND THE FEDERAL GOVERNMENT - 11052

    Energy Technology Data Exchange (ETDEWEB)

    Bergren, C.; Flora, M.; Belencan, H.

    2010-11-17

    The Savannah River Site (SRS) is a 310-square-mile United States Department of Energy nuclear facility located along the Savannah River (SRS) near Aiken, South Carolina. Nuclear weapons material production began in the early 1950s, utilizing five production reactors. In the early 1990s all SRS production reactor operations were terminated. The first reactor closure end state declaration was recently institutionalized in a Comprehensive Environmental Response and Compensation and Liability Act (CERCLA) Early Action Record of Decision. The decision for the final closure of the 318,000 square foot 105-P Reactor was determined to be in situ decommissioning (ISD). ISD is an acceptable and cost effective alternative to off-site disposal for the reactor building, which will allow for consolidation of remedial action wastes generated from other cleanup activities within the P Area. ISD is considered protective by the regulators, U. S. Environmental Protection Agency (US EPA) and the South Carolina Department of Health and Environmental Control (SCDHEC), public and stakeholders as waste materials are stabilized/immobilized, and radioactivity is allowed to naturally decay, thus preventing future exposure to the environment. Stakeholder buy-in was critical in the upfront planning in order to achieve this monumental final decision. Numerous public meetings and workshops were held in two different states (covering a 200 mile radius) with stakeholder and SRS Citizens Advisory Board participation. These meetings were conducted over an eight month period as the end state decision making progressed. Information provided to the public evolved from workshop to workshop as data became available and public input from the public meetings were gathered. ISD is being considered for the balance of the four SRS reactors and other hardened facilities such as the chemical Separation Facilities (canyons).

  11. Requirement for lamin B receptor and its regulation by importin {beta} and phosphorylation in nuclear envelope assembly during mitotic exit.

    Science.gov (United States)

    Lu, Xuelong; Shi, Yang; Lu, Quanlong; Ma, Yan; Luo, Jia; Wang, Qingsong; Ji, Jianguo; Jiang, Qing; Zhang, Chuanmao

    2010-10-22

    Lamin B receptor (LBR), a chromatin and lamin B-binding protein in the inner nuclear membrane, has been proposed to target the membrane precursor vesicles to chromatin mediated by importin β during the nuclear envelope (NE) assembly. However, the mechanisms for the binding of LBR with importin β and the membrane targeting by LBR in NE assembly remain largely unknown. In this report, we show that the amino acids (aa) 69-90 of LBR sequences are required to bind with importin β at aa 45-462, and the binding is essential for the NE membrane precursor vesicle targeting to the chromatin during the NE assembly at the end of mitosis. We also show that this binding is cell cycle-regulated and dependent on the phosphorylation of LBR Ser-71 by p34(cdc2) kinase. RNAi knockdown of LBR causes the NE assembly failure and abnormal chromatin decondensation of the daughter cell nuclei, leading to the daughter cell death at early G(1) phase by apoptosis. Perturbation of the interaction of LBR with importin β by deleting the LBR N-terminal spanning region or aa 69-73 also induces the NE assembly failure, the abnormal chromatin decondensation, and the daughter cell death. The first transmembrane domain of LBR promotes the NE production and expansion, because overexpressing this domain is sufficient to induce membrane overproduction of the NE. Thus, these results demonstrate that LBR targets the membrane precursor vesicles to chromatin by interacting with importin β in a LBR phosphorylation-dependent manner during the NE assembly at the end of mitosis and that the first transmembrane domain of LBR promotes the LBR-bearing membrane production and the NE expansion in interphase.

  12. The Bile Acid Nuclear Receptor FXRα Is a Critical Regulator of Mouse Germ Cell Fate

    Directory of Open Access Journals (Sweden)

    Emmanuelle Martinot

    2017-07-01

    Full Text Available Spermatogenesis is the process by which spermatozoa are generated from spermatogonia. This cell population is heterogeneous, with self-renewing spermatogonial stem cells (SSCs and progenitor spermatogonia that will continue on a path of differentiation. Only SSCs have the ability to regenerate and sustain spermatogenesis. This makes the testis a good model to investigate stem cell biology. The Farnesoid X Receptor alpha (FXRα was recently shown to be expressed in the testis. However, its global impact on germ cell homeostasis has not yet been studied. Here, using a phenotyping approach in Fxrα−/− mice, we describe unexpected roles of FXRα on germ cell physiology independent of its effects on somatic cells. FXRα helps establish and maintain an undifferentiated germ cell pool and in turn influences male fertility. FXRα regulates the expression of several pluripotency factors. Among these, in vitro approaches show that FXRα controls the expression of the pluripotency marker Lin28 in the germ cells.

  13. Between regulation and self-regulation - On elaboration of European grid codices in the energy sector; Zwischen Regulierung und Selbstregulierung - Zur Ausarbeitung europaeischer Netzkodizes im Energiesektor

    Energy Technology Data Exchange (ETDEWEB)

    Fischerauer, Sven [Becker Buettner Held, Bruessel (Belgium)

    2012-10-15

    The third internal market for the energy sector from 2009 obliges the operators of transmission lines and transmission systems for cross-border cooperation in a European Network of Transmission System Operators (ENTSO electricity) and Transmission System Operators (ENTSO for Gas). Its most important activity is the development of grid codices for cross-border issues of the network access. Currently, a number of draft of network codes is discussed.

  14. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  15. Food culture in the home environment: family meal practices and values can support healthy eating and self-regulation in young people in four European countries.

    Science.gov (United States)

    de Wit, John B F; Stok, F Marijn; Smolenski, Derek J; de Ridder, Denise D T; de Vet, Emely; Gaspar, Tania; Johnson, Fiona; Nureeva, Lyliya; Luszczynska, Aleksandra

    2015-03-01

    Overweight epidemics, including among children and adolescents, are fuelled by contemporary obesogenic environments. Recent research and theory highlight the importance of socio-cultural factors in mitigating adverse impacts of the abundance of food in high-income countries. The current study examines whether family meal culture shapes young people's eating behaviors and self-regulation. Young people aged 10-17 years were recruited through schools in four European countries: the Netherlands, Poland, Portugal and the United Kingdom. A total of 2,764 participants (mean age 13.2 years; 49.1% girls) completed a self-report questionnaire in class, providing information on healthy and unhealthy eating, joint family meals and communal meal values and use of eating-related self-regulation strategies. Path analysis found that family meal culture variables were significantly associated with young people's eating behaviors, as was self-regulation. Significant indirect effects of family meal culture were also found, through self-regulation. Results confirm that family meal culture, encompassing values as well as practices, shapes young people's eating behaviors. Findings extend and link previously separate lines of enquiry by showing how food cultures can play out in the home environment. Importantly, the study contributes novel evidence suggesting that self-regulation is shaped by the home environment and mediates its influence. © 2014 The International Association of Applied Psychology.

  16. Is Canada odd? A comparison of European and Canadian approaches to choice and regulation of the public/private divide in health care.

    Science.gov (United States)

    Flood, Colleen M; Haugan, Amanda

    2010-07-01

    Choice is often touted as a means for change within health care systems. Yet 'choice', in this context, takes at least three distinct forms: choice between providers within a publicly funded health care system; choice between competing insurers within a universal plan; and, lastly, choice as between privately financed health care and universal public coverage. In Canada, it is this last form of choice that is under active debate; particularly in light of the Supreme Court of Canada's decision in Chaoulli, which found a regulation banning private health insurance for medically necessary care was unconstitutional. The argument is frequently made that Canada is an outlier from other countries in having regulation that effectively precludes this kind of choice. This issue is likely to become of concern again in upcoming constitutional challenges where applicants are looking to overturn through judicial challenges Canada's medicare system. This article tests that argument of whether Canada truly is 'odd' from a comparative policy perspective by exploring regulation of choice of privately financed health care in several European countries - the Netherlands, Germany, Sweden, England and France. We highlight commonalities as well as differences, showing the extent to which these countries employ regulation to fetter growth of a large privately financed sector. The article's thesis is that Canada, in employing more intrusive forms of regulation, is not an outlier per se but at one point in a regulatory spectrum.

  17. Niacin and Selenium Attenuate Sepsis-Induced Lung Injury by Up-Regulating Nuclear Factor Erythroid 2-Related Factor 2 Signaling.

    Science.gov (United States)

    Kwon, Woon Yong; Suh, Gil Joon; Kim, Kyung Su; Jung, Yoon Sun; Kim, Sung Hee; Kim, Jae Seong; You, Kyoung Min

    2016-06-01

    To determine whether the combination therapy of niacin and selenium attenuates lung injury and improves survival during sepsis in rats and whether its benefits are associated with the activation of the glutathione redox cycle and up-regulation of nuclear factor erythroid 2-related factor 2. Prospective laboratory study. University laboratory. Human lung microvascular endothelial cells and male Sprague-Dawley rats (n = 291). In lipopolysaccharide-exposed cells, the dose-related effects of niacin and selenium were assessed, and the therapeutic effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 μM) were evaluated. The role of nuclear factor erythroid 2-related factor 2 was determined using nuclear factor erythroid 2-related factor 2 knockdown cells. In endotoxemic and cecal ligation and puncture with antibiotics rats, the therapeutic effects of the posttreatments of clinically relevant doses of niacin (360 mg/kg) and selenium (60 μg/kg) were evaluated. Combination therapy reduced the hydrogen peroxide level via the synergistic activation of the glutathione redox cycle, which involves niacin-induced increases in glutathione reductase activity, and reduced the glutathione level and a selenium-induced increase in glutathione peroxidase activity. Combination therapy contributed to the up-regulation of nuclear factor erythroid 2-related factor 2, enhancement of glutathione synthesis, and down-regulation of nuclear factor κB signaling, but nuclear factor erythroid 2-related factor 2 knockdown inhibited the enhancement of glutathione synthesis and down-regulation of the nuclear factor κB pathway. The therapeutic effects of combination therapy on endotoxemic rats were consistent with those on lipopolysaccharide-exposed cells. In addition, the posttreatment of combination therapy attenuated lung injury and improved survival in endotoxemic and cecal ligation and puncture with antibiotics rats. However, individual therapies of niacin or selenium

  18. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development

    Science.gov (United States)

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C.; Hedgepeth, John W.; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E.; Amacher, Sharon L.; Goessling, Wolfram

    2016-01-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic versus pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  19. A unigene set for European beech (Fagus sylvatica L.) and its use to decipher the molecular mechanisms involved in dormancy regulation.

    Science.gov (United States)

    Lesur, Isabelle; Bechade, Alison; Lalanne, Céline; Klopp, Christophe; Noirot, Céline; Leplé, Jean-Charles; Kremer, Antoine; Plomion, Christophe; Le Provost, Grégoire

    2015-09-01

    Systematic sequencing is the method of choice for generating genomic resources for molecular marker development and candidate gene identification in nonmodel species. We generated 47,357 Sanger ESTs and 2.2M Roche-454 reads from five cDNA libraries for European beech (Fagus sylvatica L.). This tree species of high ecological and economic value in Europe is among the most representative trees of deciduous broadleaf forests. The sequences generated were assembled into 21,057 contigs with MIRA software. Functional annotations were obtained for 85% of these contigs, from the proteomes of four plant species, Swissprot accessions and the Gene Ontology database. We were able to identify 28,079 in silico SNPs for future marker development. Moreover, RNAseq and qPCR approaches identified genes and gene networks regulated differentially between two critical phenological stages preceding vegetative bud burst (the quiescent and swelling buds stages). According to climatic model-based projection, some European beech populations may be endangered, particularly at the southern and eastern edges of the European distribution range, which are strongly affected by current climate change. This first genomic resource for the genus Fagus should facilitate the identification of key genes for beech adaptation and management strategies for preserving beech adaptability. © 2015 John Wiley & Sons Ltd.

  20. Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese Europeans: the NUGENOB study

    DEFF Research Database (Denmark)

    Corpeleijn, Eva; Petersen, Liselotte; Holst, Claus

    2010-01-01

    subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, -178 A>C CD36 (rs2232169) (P = 0.02), -22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0...

  1. [Regulations of the ethical evaluation system of scientific and clinical research in connection with Poland joining the European Union].

    Science.gov (United States)

    Raszeja, Stefan

    2004-01-01

    The author has discussed the procedures of the Bioethical Commission of a biomedical research assessment and clinical trials based on analysis of the directives of the European Commission. Particularly criticized was the omission of the role of local committees in the case of the multi-center studies. Also underlined was a necessity to inform the examined persons, in a wider and more understandable fashion, about an essence of the examination and the expected level of risk.

  2. How Have European Union Regulation Tools on Maritime Safety Developed After the Prestige Catastrophe? A Special Reference to Spain

    Directory of Open Access Journals (Sweden)

    Fernando González Laxe

    2005-06-01

    Full Text Available Maritime transport (specially when it comes to carrying hydrocarbons and dangerous products is included in the economic globalisation process. The Prestige accident in the Galician coast, Spain, has shown the existence of significant failures on part of both the market and the public sector, which leads to conclude that maritime security should be considered as a global public good. Consequently, this paper shows the advances and the still unfinished tasks according to the aforementioned view, mainly in the European Union.

  3. The liberalization and (re)regulation of gambling in the Netherlands: National consequences of the changing European context

    NARCIS (Netherlands)

    Kingma, S.F.

    2008-01-01

    This paper deals with the liberalization of Dutch gambling markets, in particular the (re)regulation of these markets after 2002. It is argued that during the 1990s a neo-liberal "risk regime" of gambling regulation replaced the traditional moralizing and restrictive gambling policies. However, this

  4. Expression and functional regulation of the nuclear receptors AHR, PXR, and CAR, and the transcription factor Nrf2 in rat parotid gland.

    Science.gov (United States)

    Droździk, Agnieszka; Wajda, Anna; Łapczuk, Joanna; Laszczyńska, Maria

    2014-08-01

    Nuclear receptors and transcription factors regulate the functions of many genes involved in cellular physiology and pathology (e.g. tumorigenesis and autoimmune diseases). The present study was performed to define the expression and the regulation of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), and nuclear factor E2-related factor 2 (Nrf2) in the rat parotid gland. Constitutive expression, as well as expression after stimulation with specific inducers for AhR [2,3,7,8-tetrachloro-dibenzylo-p-dioxin (TCDD)], Nrf2(oltipraz), PXR (dexamethasone), and CAR (phenobarbital), was evaluated using the quantitative PCR. Cellular localization of the nuclear receptors and the transcription factor was visualized by immunohistochemical staining. The study revealed constitutive expression of AhR as well as Nrf2, and their induction by TCDD andoltipraz, respectively. Immunohistochemical analysis revealed constitutive, predominantly cytoplasmic, expression of the AhR receptor, especially in interlobular striated duct cells, with nuclear shift upon exposure to TCDD. Inducible expression of Nfr2 was found mainly in the cytoplasm of intralobular striated duct cells. Constitutive expression of PXR and CAR was not found. Bearing in mind the involvement of AhR and Nrf2 in the regulation of many genes, it seems that these factors may play also a role in salivary gland physiology and pathology.

  5. Nuclear Import of the Parsley bZIP Transcription Factor CPRF2 Is Regulated by Phytochrome Photoreceptors

    Science.gov (United States)

    Kircher, Stefan; Wellmer, Frank; Nick, Peter; Rügner, Alexander; Schäfer, Eberhard; Harter, Klaus

    1999-01-01

    In plants, light perception by photoreceptors leads to differential expression of an enormous number of genes. An important step for differential gene expression is the regulation of transcription factor activities. To understand these processes in light signal transduction we analyzed the three well-known members of the common plant regulatory factor (CPRF) family from parsley (Petroselinum crispum). Here, we demonstrate that these CPRFs, which belong to the basic- region leucine-zipper (bZIP) domain-containing transcription factors, are differentially distributed within parsley cells, indicating different regulatory functions within the regulatory networks of the plant cell. In particular, we show by cell fractionation and immunolocalization approaches that CPRF2 is transported from the cytosol into the nucleus upon irradiation due to action of phytochrome photoreceptors. Two NH2-terminal domains responsible for cytoplasmic localization of CPRF2 in the dark were characterized by deletion analysis using a set of CPRF2-green fluorescent protein (GFP) gene fusion constructs transiently expressed in parsley protoplasts. We suggest that light-induced nuclear import of CPRF2 is an essential step in phytochrome signal transduction. PMID:9922448

  6. Clinical significance of the nuclear receptor co-regulator DC-SCRIPT in breast cancer: an independent retrospective validation study.

    Science.gov (United States)

    Sieuwerts, Anieta M; Ansems, Marleen; Look, Maxime P; Span, Paul N; de Weerd, Vanja; van Galen, Anne; Foekens, John A; Adema, Gosse J; Martens, John Wm

    2010-01-01

    In this study we aimed to validate the prognostic value of DC-SCRIPT mRNA expression in a large independent breast cancer cohort. In addition, since DC-SCRIPT is a transcriptional co-regulator of nuclear receptors, we explored its prognostic value in relation to estrogen-receptor-α (ESR1) and -β (ESR2) and evaluated its predictive value for response to tamoxifen treatment. DC-SCRIPT mRNA levels were measured by real-time PCR in 1,505 primary invasive breast cancers and associated with outcome (disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS)) using univariate and multivariable Cox regression analysis. Logistic and Cox regressions were used to associate DC-SCRIPT levels with clinical benefit and progression-free survival (PFS) for 296 patients treated with first-line systemic tamoxifen for advanced disease. In univariate and multivariable analysis higher DC-SCRIPT levels were associated with a favorable outcome for both the entire cohort and patients with lymph node-negative (LNN) disease that did not receive adjuvant therapy (DFS, MFS and OS; all, P SCRIPT is indeed an independent, pure prognostic, factor for primary breast cancer and shows that DC-SCRIPT mRNA expression is most informative for either ESR1-positive and/or ESR2-low pT1 tumors.

  7. Prefoldins Negatively Regulate Cold Acclimation in Arabidopsis thaliana by Promoting Nuclear Proteasome-Mediated HY5 Degradation.

    Science.gov (United States)

    Perea-Resa, Carlos; Rodríguez-Milla, Miguel A; Iniesto, Elisa; Rubio, Vicente; Salinas, Julio

    2017-06-05

    The process of cold acclimation is an important adaptive response whereby many plants from temperate regions increase their freezing tolerance after being exposed to low non-freezing temperatures. The correct development of this response relies on proper accumulation of a number of transcription factors that regulate expression patterns of cold-responsive genes. Multiple studies have revealed a variety of molecular mechanisms involved in promoting the accumulation of these transcription factors. Interestingly, however, the mechanisms implicated in controlling such accumulation to ensure their adequate levels remain largely unknown. In this work, we demonstrate that prefoldins (PFDs) control the levels of HY5, an Arabidopsis transcription factor with a key role in cold acclimation by activating anthocyanin biosynthesis, in response to low temperature. Our results show that, under cold conditions, PFDs accumulate into the nucleus through a DELLA-dependent mechanism, where they interact with HY5, triggering its ubiquitination and subsequent degradation. The degradation of HY5 would result, in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate development of cold acclimation. These findings uncover an unanticipated nuclear function for PFDs in plant responses to abiotic stresses. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  8. Nuclear factor-I regulates glial fibrillary acidic protein gene expression in astrocytes differentiated from cortical precursor cells.

    Science.gov (United States)

    Cebolla, Beatriz; Vallejo, Mario

    2006-05-01

    The elucidation of the transcriptional mechanisms that regulate glial fibrillary acidic protein (GFAP) gene expression is important for the understanding of the molecular mechanisms that control astrocyte differentiation during brain development. We investigated regulatory elements located in a proximal region of the GFAP promoter, important for expression in cortical precursor cells differentiating into astrocytes. One of these elements recognizes transcription factors of the nuclear factor-I family (NFI). We found that, in primary cultures of cortical cells, NFI occupies the GFAP promoter prior to the induction of astrocyte differentiation. In the developing cerebral cortex, the onset of expression of NFI coincides chronologically with the beginning of astrocytogenesis. Mutational analysis of the GFAP gene and transfections in primary cortical precursors show that inhibition of binding of NFI to the GFAP promoter results in decreased levels of transcriptional activity and is required for the synergistic stimulation of the GFAP promoter by the astrogenic agents, pituitary adenylate cyclase-activating polypeptide and ciliary neurotrophic factor, which in combination enhance astrocyte differentiation to generate astrocytes with longer processes. Thus, NFI appears to be an important factor for the integration of astrogenic stimuli in the developing central nervous system.

  9. Identification of a Hormone-regulated Dynamic Nuclear Actin Network Associated with Estrogen Receptor α in Human Breast Cancer Cell Nuclei*

    Science.gov (United States)

    Ambrosino, Concetta; Tarallo, Roberta; Bamundo, Angela; Cuomo, Danila; Franci, Gianluigi; Nassa, Giovanni; Paris, Ornella; Ravo, Maria; Giovane, Alfonso; Zambrano, Nicola; Lepikhova, Tatiana; Jänne, Olli A.; Baumann, Marc; Nyman, Tuula A.; Cicatiello, Luigi; Weisz, Alessandro

    2010-01-01

    Estrogen receptor α (ERα) is a modular protein of the steroid/nuclear receptor family of transcriptional regulators that upon binding to the hormone undergoes structural changes, resulting in its nuclear translocation and docking to specific chromatin sites. In the nucleus, ERα assembles in multiprotein complexes that act as final effectors of estrogen signaling to the genome through chromatin remodeling and epigenetic modifications, leading to dynamic and coordinated regulation of hormone-responsive genes. Identification of the molecular partners of ERα and understanding their combinatory interactions within functional complexes is a prerequisite to define the molecular basis of estrogen control of cell functions. To this end, affinity purification was applied to map and characterize the ERα interactome in hormone-responsive human breast cancer cell nuclei. MCF-7 cell clones expressing human ERα fused to a tandem affinity purification tag were generated and used to purify native nuclear ER-containing complexes by IgG-Sepharose affinity chromatography and glycerol gradient centrifugation. Purified complexes were analyzed by two-dimensional DIGE and mass spectrometry, leading to the identification of a ligand-dependent multiprotein complex comprising β-actin, myosins, and several proteins involved in actin filament organization and dynamics and/or known to participate in actin-mediated regulation of gene transcription, chromatin dynamics, and ribosome biogenesis. Time course analyses indicated that complexes containing ERα and actin are assembled in the nucleus early after receptor activation by ligands, and gene knockdown experiments showed that gelsolin and the nuclear isoform of myosin 1c are key determinants for assembly and/or stability of these complexes. Based on these results, we propose that the actin network plays a role in nuclear ERα actions in breast cancer cells, including coordinated regulation of target gene activity, spatial and functional

  10. Identification of a hormone-regulated dynamic nuclear actin network associated with estrogen receptor alpha in human breast cancer cell nuclei.

    Science.gov (United States)

    Ambrosino, Concetta; Tarallo, Roberta; Bamundo, Angela; Cuomo, Danila; Franci, Gianluigi; Nassa, Giovanni; Paris, Ornella; Ravo, Maria; Giovane, Alfonso; Zambrano, Nicola; Lepikhova, Tatiana; Jänne, Olli A; Baumann, Marc; Nyman, Tuula A; Cicatiello, Luigi; Weisz, Alessandro

    2010-06-01

    Estrogen receptor alpha (ERalpha) is a modular protein of the steroid/nuclear receptor family of transcriptional regulators that upon binding to the hormone undergoes structural changes, resulting in its nuclear translocation and docking to specific chromatin sites. In the nucleus, ERalpha assembles in multiprotein complexes that act as final effectors of estrogen signaling to the genome through chromatin remodeling and epigenetic modifications, leading to dynamic and coordinated regulation of hormone-responsive genes. Identification of the molecular partners of ERalpha and understanding their combinatory interactions within functional complexes is a prerequisite to define the molecular basis of estrogen control of cell functions. To this end, affinity purification was applied to map and characterize the ERalpha interactome in hormone-responsive human breast cancer cell nuclei. MCF-7 cell clones expressing human ERalpha fused to a tandem affinity purification tag were generated and used to purify native nuclear ER-containing complexes by IgG-Sepharose affinity chromatography and glycerol gradient centrifugation. Purified complexes were analyzed by two-dimensional DIGE and mass spectrometry, leading to the identification of a ligand-dependent multiprotein complex comprising beta-actin, myosins, and several proteins involved in actin filament organization and dynamics and/or known to participate in actin-mediated regulation of gene transcription, chromatin dynamics, and ribosome biogenesis. Time course analyses indicated that complexes containing ERalpha and actin are assembled in the nucleus early after receptor activation by ligands, and gene knockdown experiments showed that gelsolin and the nuclear isoform of myosin 1c are key determinants for assembly and/or stability of these complexes. Based on these results, we propose that the actin network plays a role in nuclear ERalpha actions in breast cancer cells, including coordinated regulation of target gene

  11. Regulator process for the authorization of an amendment to the operation license of a nuclear power plant in Mexico; Proceso regulador para la autorizacion de una enmienda a la licencia de operacion de una central nuclear en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Perez, R.; Espinosa V, J.M.; Salgado, J.R.; Mamani, Y.R. [CNSNS, Dr. Barragan 779, Col. Narvarte, 03020 Mexico D.F. (Mexico)

    2005-07-01

    The regulator process by which an authorization is granted from an amendment to the License of Operation of a nuclear power station in Mexico is described. It makes an appointment the effective legal mark, the technical characteristics of the modification, the evaluation process and deposition upon oath of tests and finally the elaboration of the Safety report and the Technical Verdict that is a correspondent for the regulator organism to the Secretary of Energy, the one that in turn is the responsible of granting the amendment the License just as it establishes it the Law. (Author)

  12. Regulation of nuclear envelope dynamics via APC/C is necessary for the progression of semi-open mitosis in Schizosaccharomyces japonicus.

    Science.gov (United States)

    Aoki, Keita; Shiwa, Yuh; Takada, Hiraku; Yoshikawa, Hirofumi; Niki, Hironori

    2013-09-01

    Three types of mitosis, which are open, closed or semi-open mitosis, function in eukaryotic cells, respectively. The open mitosis involves breakage of the nuclear envelope before nuclear division, whereas the closed mitosis proceeds with an intact nuclear envelope. To understand the mechanism and significance of three types of mitotic division in eukaryotes, we investigated the process of semi-open mitosis, in which the nuclear envelope is only partially broken, in the fission yeast Schizosaccharomyces japonicus. In anaphase-promoting complex/cyclosome (APC/C) mutants of Sz. japonicus, the nuclear envelope remained relatively intact during anaphase, resulting in impaired semi-open mitosis. As a suppressor of apc2 mutant, a mutation of Oar2, which was a 3-oxoacyl-[acyl carrier protein] reductase, was obtained. The level of the Oar2, which had two destruction-box motifs recognized by APC/C, was increased in APC/C mutants. Furthermore, the defective semi-open mitosis observed in an apc2 mutant was restored by mutated oar2+. Based on these findings, we propose that APC/C regulates the dynamics of the nuclear envelope through degradation of Oar2 dependent on APC/C during the metaphase-to-anaphase transition of semi-open mitosis in Sz. japonicus. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  13. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth?

    DEFF Research Database (Denmark)

    Putrik, Polina; Ramiro, Sofia; Kvien, Tore K

    2014-01-01

    To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare....

  14. Critical analysis of the European Union directive which regulates the use of biofuels. An approach to the Spanish case

    Energy Technology Data Exchange (ETDEWEB)

    Sobrino, Fernando Hernandez; Monroy, Carlos Rodriguez [Department of Business Administration, School of Industrial Engineering, Universidad Politecnica de Madrid, Jose Gutierrez Abascal, 2, 28006 Madrid (Spain)

    2009-12-15

    For more than a decade we have lived in a period where the so-called 'sustainability' is crucial and is motivated primarily by the social awareness of achieving a balance between human development and the conservation of the environment. This philosophy has a direct and inevitable impact on business and politics. Governments have long since been developing standards and encouraging various diverse initiatives whose aim is to defend the environment. In recent times, the global debate on the environment has been centred on CO{sub 2} emissions. This gas is the major cause of the 'greenhouse effect' and people are more concerned with the idea that the emissions of this gas should be minimized. As a result of this concern, the Kyoto Protocol was enacted and subscribed to by many countries, setting the maximum gas emissions for them. Fossil fuels are a major source of CO{sub 2} emissions. In 2003 the European Union (EU) directive 2003/30/EC [2003/30/EC Directive of the European Parliament and the Council - 8th may 2003. On the promotion of the use of biofuels or other renewable fuels for transport] was developed with the aim of promoting the use of biofuels as a substitute for diesel or petrol among European Union countries as well as to contribute to fulfilling the commitments on climate change, security of supply in environmentally friendly conditions and the promotion of renewable energy sources. In order to achieve these goals, the directive forces all EU members to ensure that at least 5.75% of all petrol and diesel fuels sold for transport purposes are biofuels before December 31 of 2010. European Union countries have social and economic characteristics unique to themselves. The energy dependence from foreign sources, the features of the agricultural sector or the degree of industrialization varies greatly from one country to another. In this context, it is questionable whether the obligation imposed by this directive applies to achieve