WorldWideScience

Sample records for 5p governance strategy

  1. Enacting Governance through Strategy

    DEFF Research Database (Denmark)

    Brandtner, Christof; Höllerer, Markus A.; Meyer, Renate E.

    2017-01-01

    Over the past two decades, research has emphasised a shift from city government to urban governance. Such a shift brings about its very own challenges, namely governance gaps, uncertain configurations in governance and a limited capacity to act. In this paper, we argue that the concurrent rise...... of strategy documents in city administration addresses these challenges. Our central claim is that strategy documents can be understood as a distinct discursive device through which local governments enact aspired governance configurations. We illustrate our argument empirically using two prominent examples...... that, while showing similar features and characteristics, are anchored in different administrative traditions and institutional frameworks: the city administrations of Sydney, Australia, and Vienna, Austria. The contribution of the paper is to show how strategy documents enact governance configurations...

  2. Facilitation as a governance strategy: Unravelling governments' facilitation frames

    NARCIS (Netherlands)

    Grotenbreg, S. (Sanne); M.W. van Buuren (Arwin)

    2017-01-01

    textabstractGovernments increasingly choose facilitation as a strategy to entice others to produce public goods and services, including in relation to the realisation of sustainable energy innovations. An important instrument to implement this governance strategy is discursive framing. To learn how

  3. HUD Digital Government Strategy Report

    Data.gov (United States)

    Department of Housing and Urban Development — The HUD Digital Strategic Plan clearly articulates the goals of openness and transparency, furthering the innovation economy and meeting more global government wide...

  4. Electronic government: rethinking channel management strategies

    NARCIS (Netherlands)

    Ebbers, W.E.; Pieterson, W.J.; Noordman, H.N.

    2008-01-01

    This article explores how an alternative multichannel management strategy can improve the way governments and citizens interact. Improvement is necessary because, based on empirical data from various sources, the conclusion can be drawn that there is a gap between the communication channels governme

  5. Innovative Governance Strategies in Meetings Destination Networks

    DEFF Research Database (Denmark)

    Gyimóthy, Szilvia; Larson, Mia

    2013-01-01

    Innovative Governance Strategies in Meetings Destination Networks Introduction, problem statement and aims of the study Collaborative regional networks has been long considered as a must in successful tourism development (Dredge & Jenkins 2003) owing to benefits such as scale and scope economics......, as well as joint planning and coordination of supply facilities. However, the setting up and governance of destination networks is paved with managerial challenges, including, among others: the balancing of conflicting stakeholder interest (Wilkinson & March 2008), and bridging over the gap between...... on a comparative analysis of Convention Bureaus (CVBs) and the network around them in the two cities, the study sheds light on governance strategies adopted by the convenors in order to mobilize meetings industry stakeholders across cultural, institutional and political borders. Conceptual approach The theoretical...

  6. E-governance innovation: Barriers and strategies

    NARCIS (Netherlands)

    Meijer, Albert

    2015-01-01

    Various models have been developed to explain the adoption of e-government but systematic research on barriers to e-governance is lacking. On the basis of the literature, this paper develops a theoretical model of e-governance innovation that highlights (1) phases in the innovation process, (2) gove

  7. Information Strategies for Open Government: Challenges and Prospects for Deriving Public Value from Government Transparency

    OpenAIRE

    Sharon S. Dawes; Helbig, Natalie

    2010-01-01

    International audience; Information-based strategies to promote open government offer many opportunities to generate social and economic value through public use of government information. Public and political expectations for the success of these strategies are high but they confront the challenges of making government data "fit for use" by a variety of users outside the government. Research findings from a study of public use of land records demonstrates the inherent complexity of public us...

  8. Defining decision making strategies in software ecosystem governance

    DEFF Research Database (Denmark)

    Manikas, Konstantinos; Wnuk, Krzysztof; Shollo, Arisa

    Making the right decisions is an essential part of software ecosystem governance. Decisions related to the governance of a software ecosystem can influence the health of the ecosystem and can result in fostering the success or greatly contributing to the failure of the ecosystem. However, very few...... studies touch upon the decision making of software ecosystem governance. In this paper, we propose decomposing software ecosystem governance into three activities: input or data collection, decision making, and applying actions. We focus on the decision making activity of software ecosystem governance...... and review related literature consisted of software ecosystem governance, organizational decision making, and IT governance. Based on the identified studies, we propose a framework for defining the decision making strategies in the governance of software ecosystems. We identify five decision areas...

  9. Defining decision making strategies in software ecosystem governance

    DEFF Research Database (Denmark)

    Manikas, Konstantinos; Wnuk, Krzysztof; Shollo, Arisa

    studies touch upon the decision making of software ecosystem governance. In this paper, we propose decomposing software ecosystem governance into three activities: input or data collection, decision making, and applying actions. We focus on the decision making activity of software ecosystem governance......Making the right decisions is an essential part of software ecosystem governance. Decisions related to the governance of a software ecosystem can influence the health of the ecosystem and can result in fostering the success or greatly contributing to the failure of the ecosystem. However, very few...... and review related literature consisted of software ecosystem governance, organizational decision making, and IT governance. Based on the identified studies, we propose a framework for defining the decision making strategies in the governance of software ecosystems. We identify five decision areas...

  10. 76 FR 29195 - National Strategy for Trusted Identities in Cyberspace (NSTIC) Governance Workshop

    Science.gov (United States)

    2011-05-20

    ... (NSTIC) Governance Workshop AGENCY: National Institute of Standards & Technology (NIST), Commerce. ACTION... Cyberspace (NSTIC) Governance Workshop to be held on Thursday, June 9, 2011, 9 a.m. until 5 p.m. and Friday, June 10, 2011, 9 a.m. until 5 p.m. This workshop will identify and discuss various governance models...

  11. How does Corporate Governance Affect Bank Capitalization Strategies?

    NARCIS (Netherlands)

    Anginer, D.; Demirgüc-Kunt, A.; Huizinga, H.P.; Ma, K.

    2013-01-01

    Abstract: This paper examines how corporate governance and executive compensation affect bank capitalization strategies for an international sample of banks over the 2003-2011 period. ‘Good’ corporate governance, which favors shareholder interests, is found to give rise to lower bank capitalization.

  12. How does corporate governance affect bank capitalization strategies?

    NARCIS (Netherlands)

    Anginer, D.; Demirgüç-Kunt, A.; Huizinga, Harry; Ma, K.

    2016-01-01

    This paper examines how corporate governance and executive compensation affect bank capitalization strategies for an international sample of banks over the 2003-2011 period. ‘Good’ corporate governance, which favors shareholder interests, is found to give rise to lower bank capitalization. Boards of

  13. Professionalization as a governance strategy for synthetic biology.

    Science.gov (United States)

    Weir, Lorna; Selgelid, Michael J

    2009-12-01

    This article considers professionalization as a governance strategy for synthetic biology, reporting on social science interviews done with scientists, science journal editors, members of science advisory boards and authors of nongovernmental policy reports on synthetic biology. After summarizing their observations about the potential advantages and disadvantages of the professionalization of synthetic biology, we analyze professionalization as a strategy that overcomes dichotomies found in the current debates about synthetic biology governance, specifically "top down" versus "bottom up" governance and scientific fact versus public values. Professionalization combines community and state, fact and value. Like all governance options, professionalization has limitations, particularly regarding war and peace. It is best conceptualized as potentially part of a wider range of governance mechanisms working in concert: a "web of prevention".

  14. MiR675-5p Acts on HIF-1α to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma

    Science.gov (United States)

    Lo Dico, Alessia; Costa, Viviana; Martelli, Cristina; Diceglie, Cecilia; Rajata, Francesca; Rizzo, Aroldo; Mancone, Carmine; Tripodi, Marco; Ottobrini, Luisa; Alessandro, Riccardo; Conigliaro, Alice

    2016-01-01

    Hypoxia is a common feature in solid tumours. In glioma, it is considered the major driving force for tumour angiogenesis and correlates with enhanced resistance to conventional therapies, increased invasiveness and a poor prognosis for patients. Here we describe, for the first time, that miR675-5p, embedded in hypoxia-induced long non-coding RNA H19, plays a mandatory role in establishing a hypoxic response and in promoting hypoxia-mediated angiogenesis. We demonstrated, in vitro and in vivo, that miR675-5p over expression in normoxia is sufficient to induce a hypoxic moreover, miR675-5p depletion in low oxygen conditions, drastically abolishes hypoxic responses including angiogenesis. In addition, our data indicate an interaction of miR675-5p, HIF-1α mRNA and the RNA Binding Protein HuR in hypoxia-induced responses. We suggest the modulation of miR675-5p as a new therapeutic option to promote or abolish hypoxia induced angiogenesis. PMID:27279905

  15. Tax Limitations and Revenue Shifting Strategies in Local Government

    DEFF Research Database (Denmark)

    Blom-Hansen, Jens; Bækgaard, Martin; Serritzlew, Søren

    2014-01-01

    subjected to tax limitations employ revenue-shifting strategies. In Denmark, however, these strategies are contingent on the specifics of the Danish intergovernmental system, which render central government grants an attractive object of revenue-shifting strategies. Our analysis thus helps identify......The literature on tax and expenditure limitations (TELs) shows how limiting the freedom of local governments to levy taxes may have considerable unexpected effects. Entities subjected to such limitations may, as their proponents hope, react by cutting expenditures and revenue, but they may also...... the central government imposed tax limitations on municipalities in 2009, makes two contributions. First, it probes the empirical domain of the US findings. Second, it constitutes an empirical testing ground where endogeneity is not a pressing concern. In the USA, TELs are often self-imposed either by local...

  16. REDD+ policy strategy in Cameroon: Actors, institutions and governance

    NARCIS (Netherlands)

    Somorin, O.A.; Visseren-Hamakers, I.J.; Arts, B.J.M.; Sonwa, D.J.; Tiani, A.

    2014-01-01

    Reducing emissions from deforestation and forest degradation (REDD+) is receiving increasing political and scientific attention as a climate change mitigation approach. The government of Cameroon has expressed an interest in participating in REDD+, and national deliberation on a policy strategy has

  17. Regional governance: strategies and disputes in health region management

    Directory of Open Access Journals (Sweden)

    Adriano Maia dos Santos

    2014-08-01

    Full Text Available OBJECTIVE To analyze the regional governance of the health systemin relation to management strategies and disputes. METHODOLOGICAL PROCEDURES A qualitative study with health managers from 19 municipalities in the health region of Bahia, Northeastern Brazil. Data were drawn from 17 semi-structured interviews of state, regional, and municipal health policymakers and managers; a focus group; observations of the regional interagency committee; and documents in 2012. The political-institutional and the organizational components were analyzed in the light of dialectical hermeneutics. RESULTS The regional interagency committee is the chief regional governance strategy/component and functions as a strategic tool for strengthening governance. It brings together a diversity of members responsible for decision making in the healthcare territories, who need to negotiate the allocation of funding and the distribution of facilities for common use in the region. The high turnover of health secretaries, their lack of autonomy from the local executive decisions, inadequate technical training to exercise their function, and the influence of party politics on decision making stand as obstacles to the regional interagency committee’s permeability to social demands. Funding is insufficient to enable the fulfillment of the officially integrated agreed-upon program or to boost public supply by the system, requiring that public managers procure services from the private market at values higher than the national health service price schedule (Brazilian Unified Health System Table. The study determined that “facilitators” under contract to health departments accelerated access to specialized (diagnostic, therapeutic and/or surgical services in other municipalities by direct payment to physicians for procedure costs already covered by the Brazilian Unified Health System. CONCLUSIONS The characteristics identified a regionalized system with a conflictive pattern of

  18. Regional governance: strategies and disputes in health region management

    Science.gov (United States)

    dos Santos, Adriano Maia; Giovanella, Ligia

    2014-01-01

    OBJECTIVE To analyze the regional governance of the health systemin relation to management strategies and disputes. METHODOLOGICAL PROCEDURES A qualitative study with health managers from 19 municipalities in the health region of Bahia, Northeastern Brazil. Data were drawn from 17 semi-structured interviews of state, regional, and municipal health policymakers and managers; a focus group; observations of the regional interagency committee; and documents in 2012. The political-institutional and the organizational components were analyzed in the light of dialectical hermeneutics. RESULTS The regional interagency committee is the chief regional governance strategy/component and functions as a strategic tool for strengthening governance. It brings together a diversity of members responsible for decision making in the healthcare territories, who need to negotiate the allocation of funding and the distribution of facilities for common use in the region. The high turnover of health secretaries, their lack of autonomy from the local executive decisions, inadequate technical training to exercise their function, and the influence of party politics on decision making stand as obstacles to the regional interagency committee’s permeability to social demands. Funding is insufficient to enable the fulfillment of the officially integrated agreed-upon program or to boost public supply by the system, requiring that public managers procure services from the private market at values higher than the national health service price schedule (Brazilian Unified Health System Table). The study determined that “facilitators” under contract to health departments accelerated access to specialized (diagnostic, therapeutic and/or surgical) services in other municipalities by direct payment to physicians for procedure costs already covered by the Brazilian Unified Health System. CONCLUSIONS The characteristics identified a regionalized system with a conflictive pattern of governance and

  19. 2000 Johnston Site 5P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 5P was established at Johnston Atoll by Dr. James Maragos, U.S. Fish & Wildlife Service, on July 2, 2000. With a start point (meter 0) at...

  20. 2004 Rose Site 5P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 5P was established off Rose Atoll, American Samoa by Dr. James Maragos, U.S. Fish & Wildlife Service, on February 20, 2002. With a start point...

  1. 2002 Rose Site 5P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 5P was established off Rose Atoll, American Samoa by Dr. James Maragos, U.S. Fish & Wildlife Service, on February 20, 2002. With a start point...

  2. What Is Green Growth Strategy for Government Link Company?

    Science.gov (United States)

    Jamilah Asha'ari, Maryam; Daud, Salina; Hassan, Hasmaizan

    2016-03-01

    Disasters around the world are very extreme because of the global warming and climate change. Malaysia firms have to play their role in handling the challenging of environmental problems in order to sustain. The feature of the new strategy which is green growth strategy has been identified. The study focuses on the features of the green growth strategy which discuss on the keys to sustaining the strategy, marketing emphasis, production emphasis, product line, basis of competitive advantage and strategic target. Business had contributed to the industrialisation era positively or negatively and therefore there is a must for business people to use the best strategy in reducing the environmental risks. By 2020, Malaysia will achieve the target in becoming an advanced economy by applying the right strategy. The objective of this paper is to propose a feature for new strategy known as green growth strategy. Future study is to propose to conduct an empirical analysis to confirm the green growth strategy features.

  3. A New Fuzzy MCDM Framework to Evaluate E-Government Security Strategy

    CERN Document Server

    Syamsuddin, Irfan

    2010-01-01

    Ensuring security of e-government applications and infrastructures is crucial to maintain trust among stakeholders to store, process and exchange information over the e-government systems. Due to dynamic and continuous threats on e-government information security, policy makers need to perform evaluation on existing information security strategy as to deliver trusted e-government services. This paper presents an information security evaluation framework based on new fuzzy multi criteria decision making (MCDM) to help policy makers conduct comprehensive assessment of e-government security strategy.

  4. Government Financial Management, Strategy for Preventing Corruption in Indonesia

    Directory of Open Access Journals (Sweden)

    Haryono Umar

    2007-04-01

    Full Text Available In popular view, the term accountability generally refers to a wide spectrum of public expectations dealing with organizational performance, responsiveness, good governance, and even morality of government and nonprofit organizations. These expectations often include implicit performance criteria – related to obligations and responsibilities – that are subjectively interpreted and sometimes even contradictory. And in this broader conception of accountability, the range of people and institutions to whom public and nonprofit organizations must account include not only higher authorities in the institutional chain of command but also the general public, the news media, peer agencies, donors, and many other stakeholders (Kearns, 1996. Government could build its accountability by implementing good and proper financial management. Financial management is a tool for government to show its performance and accountability to the public. Meanwhile, corruption is the misuse of public office for private gain. As such, it involves the improper and unlawful behavior of public-service officials, both politicians and civil servants, whose positions create opportunities for the diversion of money and assets from government to them and their accomplices (Langseth, 1999. The more corruption, the more far away from good governance, and the less public accountability. According to Klitgaard (1988, power minus accountability is corruption. This paper explains about the influences of implementing government financial management to corruption fighting and good governance in broadly view. Discussion will be derived to find out the understanding of financial management, corruption, and good governance terminology fits for Indonesia environment. The purpose of this paper is to achieve common knowledge that financial management should be implemented by public organization from strategic management for public organization approaches. Besides, reader will find out

  5. Public information strategies: Making government information available to citizens

    NARCIS (Netherlands)

    Meijer, A.J.; Thaens, M.

    2009-01-01

    New technological opportunities and increasing demands make it imperative for government agencies to make the information they gather available to citizens. How should they go about this? This paper presents a conceptual framework for analyzing the strategic options open to agencies which have infor

  6. Selection of energy source and evolutionary stable strategies for power plants under financial intervention of government

    Science.gov (United States)

    Hafezalkotob, Ashkan; Mahmoudi, Reza

    2017-03-01

    Currently, many socially responsible governments adopt economic incentives and deterrents to manage environmental impacts of electricity suppliers. Considering the Stackelberg leadership of the government, the government's role in the competition of power plants in an electricity market is investigated. A one-population evolutionary game model of power plants is developed to study how their production strategy depends on tariffs levied by the government. We establish that a unique evolutionary stable strategy (ESS) for the population exists. Numerical examples demonstrate that revenue maximization and environment protection policies of the government significantly affect the production ESS of competitive power plants. The results reveal that the government can introduce a green energy source as an ESS of the competitive power plants by imposing appropriate tariffs.

  7. Assessment of governance strategies for climate adaptation in Flanders / Belgium

    OpenAIRE

    Verhofstede, Björn; Leinfelder, Hans; Allaert, Georges

    2010-01-01

    Climate discourse in recent decades has mainly focused on the issue of mitigation. Through a better understanding and assessment of climate challenges, adaptation arises as a complementary strategy to mitigation. Vulnerability in relation to climate change is seen as a function of exposure, sensitivity and adaptive capacity. Adaptation can influence sensitivity while mitigating impacts on the exposure to climate change. (IPCC, 2007). Adaptation requires space for climate on a local scale and ...

  8. The strategies of governance from two perspectives: capitalist enterprises versus social economy enterprises: an empirical study

    Directory of Open Access Journals (Sweden)

    María del Carmen Muñoz Medraño

    2014-05-01

    Full Text Available Companies increasingly develop strategies and implement governance models of efficient management. These systems of government are based on innovative measures, policies for social and environmental responsibility, and strategic alliances. All are being considered in recent years as efficient policies for the governance of institutions, creating value and better business results. This paper addresses good governance from a comparative analysis of capitalist enterprises and social economy to the region of Murcia. Transparency, democratic management, innovation, partnerships, among others, can make the difference between the modus operandi of these businesses and the effects thereof in the territories where they settle.

  9. Rehabilitating antisocial personalities: treatment through self-governance strategies.

    Science.gov (United States)

    McRae, Leon

    2013-02-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  10. 76 FR 50719 - Models for a Governance Structure for the National Strategy for Trusted Identities in Cyberspace...

    Science.gov (United States)

    2011-08-16

    ... National Institute of Standards and Technology Models for a Governance Structure for the National Strategy... extending the deadline for submitting comments regarding the governance structure for the National Strategy... and structure of the Identity Ecosystem governance body. The due date for submission of comments...

  11. How Corporate Governance Affects Strategy of Corporations : - Lessons from Enron Corporation -

    OpenAIRE

    Ahmed, Hameed; Najam, Ali

    2006-01-01

    Corporate governance is a subject of academic and professional debate. It has and it will continue to be a topic under scrutiny for subsequent deliberations since there are many different research dimensions and contexts associated with it. However, it has been observed that the linkage between corporate governance and strategy of a corporation remains as an untapped area with considerable avenues of research. This paper tends to explore this linkage, using Enron scandal as backdrop. In the a...

  12. The German government's global health strategy--a strategy also to support research and development for neglected diseases?

    Science.gov (United States)

    Fehr, Angela; Razum, Oliver

    2014-01-01

    Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D) deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

  13. The work plan for the newly created IUHPE Vice President for Strategy and Governance.

    Science.gov (United States)

    Sparks, Michael

    2008-12-01

    The position of Vice President for Strategy and Governance was created at the first full meeting of the International Union for Health Promotion and Education Board of Trustees in June 2007 in Vancouver, Canada. Specific duties were developed for the position and the newly elected Vice President developed a work plan for the period of 2007-10. This paper describes the responsibilities of the newly created Vice Presidency and the work plan developed to meet those responsibilities. The key action areas for the focus of the work of the Vice President for Strategy and Governance include: finalising the rewritten Strategic Directions for 2008-10; developing Strategic Directions for 2010-16; developing and implementing processes to improve the strategic coordination and reporting of work plans across the organisation; and broad responsibility for eliciting and working with the organisation to respond to governance issues.

  14. Transnational Metropolitan Development Strategies and Governance in a Post-Socialist Setting: The Case of Szczecin

    Directory of Open Access Journals (Sweden)

    Tölle Alexander

    2014-12-01

    Full Text Available The integration of cities and their regions into transnational networks has become a key municipal strategy, with the creation of a metropolitan governance structure being seen in this context as a fundamental element. The Szczecin Metropolitan Area constitutes an example of meagre results in intercommunal cooperation in post-socialist East-Central Europe. This has its repercussions on the task of creating cross-border metropolitan governance structures including adjacent German counties, a task which, in turn, may help to overcome development barriers. This becomes apparent particularly in the process of defining joint development objectives as well as an image for the cross-border metropolitan region

  15. Combining planning and the market : an analysis of the government strategy towards higher education in the Netherlands

    NARCIS (Netherlands)

    Vught, van Frans A.

    1997-01-01

    This article discusses and analyses the government strategy towards higher education in the Netherlands as it has been designed and implemented since the publication of an influential policy document in 1985. This strategy intends to be a significant break with the traditional government attitude of

  16. 欧盟的全球治理战略%The EU Strategy for Global Governance

    Institute of Scientific and Technical Information of China (English)

    杨娜

    2012-01-01

    在有效推进区域治理和积极应对全球化的进程中,欧盟也在不断构建和完善自己的全球治理战略。欧盟支持并参与国际机制的非根本性改革,以整体身份谋求在国际事务中的代表权和话语权,提高集体军事行动能力,通过提供全球公共产品担当全球公益领域治理的主导。欧盟的全球治理战略表现出包容与排外相混合、有效多边主义、关注全球公益、推广欧盟式民主等特点,但在实施过程中,也面临着决策效率低、行动能力差、内部立场不统一等诸多制约。%In the process of effectively promoting regional governance and positively addressing globalization, EU gradually constrnets and improves its own strategy for global governance. EU supports and participates in non -fundamental reforms of international institutions, strives for representation and discourse power in international affairs as a whole, enhances the capability of collective military action, assumes the leader of global public governance through providing global public goods. EU strategy for global governance demonstrates some characteristics of hybrid of inclusiveness and exclusiveness, ef- fective multilateralism, concentration on global public areas and popularization of EU style democracy. However, during executing the strategy for global governance, EU faces several restrictions like low decision - making efficiency, poor action capacity and inside disunity positions.

  17. Relationship between Marketing Strategies and Governance Mechanisms: A Study in Exploration Chain Beef Cattle

    Directory of Open Access Journals (Sweden)

    Filipe Quevedo-Silva

    2015-09-01

    Full Text Available The relationship between actors has been unspoilt by marketing through the bias of Transaction Costs Economics. Some authors suggest that a marketing strategy can directly impact the transactional characteristics and hence the governance mechanisms chosen to coordinate transactions. Studies suggest that future work in the field of marketing include, among other factors, aspects related to the relationship between the actors. In this context, this article aims to analyze how marketing strategies can affect the choice of governance mechanisms. The study object is the chain of beef, view their representation to the national economy. To this end, we conducted a qualitative study using semi-structured interviews with various actors in the chain. It was possible to verify the existence of the relationship between marketing strategy and governance structure. In one of the cases, product differentiation, translated into more specific assets, led the producer to perform a relational contract with the fridge and to distribute your product, make an integration with retailers, through the opening of a boutique of meat. Factor that was not observed in transactions involving producers on products without distinction, for which the transactions via spot market are prevalent.  

  18. Governance of globalized water resources: the application of the water footprint to inform corporate strategy and government policy

    NARCIS (Netherlands)

    Ercin, A.E.

    2012-01-01

    Managing the water footprint of humanity is something in which both governments and businesses have a key role. The actual reduction of humanity's water footprint depends on the combination of what governments, businesses and consumers do and how their different actions reinforce (or counteract) one

  19. THEORETIC INCURSION IN THE IDENTIFICATION OF DETERMINANTS AND E-GOVERNMENT STRATEGY. EMPIRIC STUDY OVER THE GRADE OF IMPLEMENTATION OF E-GOVERNMENT IN BIHOR COUNTY

    Directory of Open Access Journals (Sweden)

    Pop Cohut Ioana

    2012-07-01

    Full Text Available We are currently witnessing an unprecedented development of new technologies, that offers great opportunities for the modernization of the society, it changes radically the way governments, businesses and citizens have the opportunity to obtain goods and services, the way in which public services are provided that become increasingly important for citizens, the way of obtaining and transmitting information, the way in which business connections are done, the interaction between different communities, etc.. From this point of view we research the way in which public strategies of achievement and implementation of model of e-government are shaped, model which can exploit the opportunities offered by new technologies and can implement roles for the citizen and public policy makers and implicitly of local and regional development. How the public sector should support the implementation of strategies of e-government, to polarize at the highest level all communities of interest, to provide a framework for planning and action across the board, covering local administration, institutions, organizations and government agencies, to empower appropriate training for implementation of IT strategies, can lead to stimulation of generators factors of local and regional development. We also, intend to identify, from carrying out an empirical study in Bihor county, by analysis of 30 public institutions, the degree of implementation of new technologies in public administration, human resources readiness for appropriate use of IT facilities and what level of implementation of e-government in these institutions, in order to outline the main characteristics and determinants of e-government implementation. The present paper is of interest to policy-makers, researchers, local communities through analysis how the introduction of new technology development in developing and implementing public policies, particularly by networking government and e-government, can cause

  20. Priorities in national space strategies and governance of the member states of the European Space Agency

    Science.gov (United States)

    Adriaensen, Maarten; Giannopapa, Christina; Sagath, Daniel; Papastefanou, Anastasia

    2015-12-01

    The European Space Agency (ESA) has twenty Member States with a variety of strategic priorities and governance structures regarding their space activities. A number of countries engage in space activities exclusively though ESA, while others have also their own national space programme. Some consider ESA as their prime space agency and others have additionally their own national agency with respective programmes. The main objective of this paper is to provide an up-to date overview and a holistic assessment of strategic priorities and the national space governance structures in 20 ESA Member States. This analysis and assessment has been conducted by analysing the Member States public documents, information provided at ESA workshop on this topic and though unstructured interviews. The paper is structured to include two main elements: priorities and trends in national space strategies and space governance in ESA Member States. The first part of this paper focuses on the content and analysis of the national space strategies and indicates the main priorities and trends in Member States. The priorities are categorised with regards to technology domains, the role of space in the areas of sustainability and the motivators that boost engagement in space. These vary from one Member State to another and include with different levels of engagement in technology domains amongst others: science and exploration, navigation, Earth observation, human space flight, launchers, telecommunications, and integrated applications. Member States allocate a different role of space as enabling tool adding to the advancement of sustainability areas including: security, resources, environment and climate change, transport and communication, energy, and knowledge and education. The motivators motivating reasoning which enhances or hinders space engagement also differs. The motivators identified are industrial competitiveness, job creation, technology development and transfer, social benefits

  1. [Implementing strategies to improve the institutional governance of the Spanish National Health System].

    Science.gov (United States)

    Repullo, José Ramón; Freire, José Manuel

    2016-11-01

    The 2008 economic crisis made the issue of good governance more present and visible, but the debate risks stalling in an academic and political discourse that barely exceeds the declarative. We acknowledge the existence of noteworthy documents from scientific medical societies and some institutional proposals that point towards promising changes. Viewing good governance as accountability, participation, transparency, intelligence and integrity, our objective is to identify the determinants of inaction and remove the barriers that prevent the adoption of rational and widely agreed-upon proposals. This led us: 1) to allocate the proposals to their appropriate governance level (macro, meso, micro and system environment) so as to more directly engage the agents of change; and 2) to highlight some decision nodes that can act as levers to catalyse selective transformations and to initiate the change processes. Taking into account the diversity of actors and scenarios, a top-down rational, integrated and reformist strategy for the whole Spanish National Health System does not seem likely or viable. Therefore, the purpose of this paper is to promote changes, setting a targeted and reasoned agenda to visualise key issues and to enable multilevel and multidimensional thinking and advocacy of health-sector and society stakeholders.

  2. Imperial or postcolonial governance? Dissecting the genealogy of a global public health strategy.

    Science.gov (United States)

    Brown, Tim; Bell, Morag

    2008-11-01

    During the last decades of the 20th century it became increasingly apparent that the inter-relationship between globalisation and health is extremely complex. This complexity is highlighted in debates surrounding the re-emergence of infectious diseases, where it is recognised that the processes of globalisation have combined to create the conditions where once localised, microbial hazards have come to pose a threat to many western nations. By contrast, in an emerging literature relating to the epidemic of non-communicable diseases, and reflected in the WHO 'Global strategy on diet, physical activity and health', it is the so-called 'western lifestyle' that has been cast as the main threat to a population's health. This paper explores critically global responses to this development. Building on our interest in questions of governance and the ethical management of the healthy body, we examine whether the global strategy, in seeking to contain the influence of a 'western lifestyle', also promotes contemporary 'western-inspired' approaches to public health practices. The paper indicates that a partial reading of the WHO strategy suggests that certain countries, especially those outside the West, are being captured or 'enframed' by the integrative ambitions of a western 'imperial' vision of global health. However, when interpreted critically through a postcolonial lens, we argue that 'integration' is more complex, and that the subtle and dynamic relations of power that exist between countries of the West/non-West, are exposed.

  3. Climate change in semi-arid Malawi: Perceptions, adaptation strategies and water governance

    Directory of Open Access Journals (Sweden)

    Miriam K. Joshua

    2016-03-01

    Full Text Available Climate change and variability are a threat to sustainable agricultural production in semi-arid areas of Malawi. Overdependence on subsistence rain-fed agriculture in these areas calls for the identification of sustainable adaptation strategies. A study was therefore conducted in Chikwawa, a semi-arid district in southern Malawi, to: (1 assess community’s perception of a changing climate against empirical evidence, (2 determine their local adaptive measures, (3 evaluate the potential of irrigated agriculture as an adaptive measure in household food security and (4 challenges over access to available water resources. The study employed focus group discussions and key informant interviews to assess people’s perceptions of climate change and variability and their desired interventions. To validate the people’s perceptions, rainfall and temperature data for the period 1960–2010 were analysed. A participatory complete randomised experimental design in both rain-fed and dry season–irrigated conditions was conducted to assess a maize cropping system that would improve adaptation. The study established persistent declining yields from rain-fed production in part because of perennial rainfall failure. In response, the community has shifted its focus to irrigation as an adaptation strategy, which has in turn triggered water conflicts in the community over the control of the resource. Water legislation however fails to adequately provide for rules governing sharing of water resources between various stakeholders. This article therefore recommends development of an appropriate institutional framework that forms a strong basis for equitable distribution of water for irrigation in areas most vulnerable to extreme climate events – including droughts and floods.Keywords: Food Security; Climate Change and Variability; Rainfall Variability; Irrigation; Water Resources; Governance Crisis

  4. Contextual Factors Affecting E-Government Strategy Implementation and Its Impact on Public Sector Performance in Kenya

    Directory of Open Access Journals (Sweden)

    Dr. James Gathungu

    2013-06-01

    Full Text Available This paper assesses the contextual factors affecting the implementation of e-government strategy and its impact on the performance of the public sector in Kenya using the Wing Lam, (2005 E-government Integration Model. Electronic government (E-government is viewed in this study as the utilization of Information Communication Technologies (ICTs to transform the efficiency, effectiveness, transparency and accountability of exchanges within government, between government and citizens and businesses locally and abroad; and to empower citizens through access and use of information. Although e-government is a rapidly growing concept in both developing and developed countries very few e-government initiatives progress to maturity. Different countries are faced with different contextual circumstances and environments in the realization of e-government initiatives. This study attempts to address the gap between theory and rhetoric about the potential of e-government and the reality of its application on the ground in Kenya. The study attempts to analyze the philosophy, theories and paradigms of e-government. The development of the commercial concept as a new paradigm in public administration replacing the traditional bureaucratic systems of government is highlighted in the study. A detailed conceptual discussion anchors the study on the Wing Lam, (2005 E-government Integration Model (EGI basing it on the Kenyan perspective. The study also reviews relevant e-government studies from an international, regional and local perspective anchoring the study on the configuration school of management thought. These discussions are used to develop new insights in view of the emerging issues and their relevance to the public sector in Kenya.  

  5. Local energy governance in vermont: an analysis of energy system transition strategies and actor capacity

    Science.gov (United States)

    Rowse, Tarah

    While global, national, and regional efforts to address climate and energy challenges remain essential, local governments and community groups are playing an increasingly stronger and vital role. As an active state in energy system policy, planning and innovation, Vermont offers a testing ground for research into energy governance at the local level. A baseline understanding of the energy planning and energy organizing activities initiated at the local level can support efforts to foster a transition to a sustainable energy system in Vermont. Following an inductive, applied and participatory approach, and grounded in the fields of sustainability transitions, energy planning, and community energy, this research project identifies conditions for change, including opportunities and challenges, within Vermont energy system decision-making and governance at the local level. The following questions are posed: What are the main opportunities and challenges for sustainable energy development at the town level? How are towns approaching energy planning? What are the triggers that will facilitate a faster transition to alternative energy systems, energy efficiency initiatives, and localized approaches? In an effort to answer these questions two studies were conducted: 1) an analysis of municipal energy plans, and 2) a survey of local energy actors. Study 1 examined Vermont energy planning at the state and local level through a review and comparison of 40 municipal plan energy chapters with the state 2011 Comprehensive Energy Plan. On average, municipal plans mentioned just over half of the 24 high-level strategies identified in the Comprehensive Energy Plan. Areas of strong and weak agreement were examined. Increased state and regional interaction with municipal energy planners would support more holistic and coordinated energy planning. The study concludes that while municipalities are keenly aware of the importance of education and partnerships, stronger policy mechanisms

  6. Zhengdong New District Smart Government Application System Construction and Its Development Strategy Research

    Directory of Open Access Journals (Sweden)

    Li Bing

    2017-01-01

    Full Text Available Smart government is the advanced stage of e-government development, whose essence is the fusion of Internet, Internet of things, cloud computing, big data and other high and new technology and e-government, to achieve the efficient management of all kinds of information resources and make the government services more transparent, scientific and wisdom. Based on the introduce, basic principle and construct meaning, application system construction, main problems and developing countermeasures and other aspects of smart government to make a comprehensive analysis in the construction of Zhengdong new district smart government, then advise the government departments to speed up the transformation of government management functions and social service mode to integrate the business processes, and promote the construction of service-oriented and smart-oriented government actively.

  7. Corporate governance and firm performance : An analysis of ownership structure, profit redistribution and diversification strategies of firms in India

    NARCIS (Netherlands)

    George, R.

    2005-01-01

    This dissertation examines the relationship between corporate governance and performance of firms in India. Utilizing various theoretical bases in strategy and finance domains, the dissertation attempts to distill a better understanding of the pivotal role played by the twin dimensions of ownership

  8. The Government Subsidy Strategy Choice for Firm’s R&D: Input Subsidy or Product Subsidy?

    Directory of Open Access Journals (Sweden)

    Zhiying Liu

    2014-01-01

    Full Text Available To encourage enterprises to conduct technology innovation, the government needs to formulate appropriate subsidies policy. This paper compares two R&D subsidy policies in a supplier-manufacturer supply chain, in which the manufacturer conducts R&D activity for quality improvement. By means of game theory, we investigate the optimal decisions of the players under the two R&D subsidy policies, that is, input subsidy policy and product subsidy policy. Finally, we compare the profits and welfare to explore the better R&D subsidy policy and provide decision support for government to formulate subsidy policy. The results show that under input subsidy policy the optimal production output, quality improvement, profits, government subsidies, and social welfare are all lower than those of product subsidy policy. Therefore, the government should use product subsidy strategy to encourage enterprise R&D activities.

  9. Cloud Computing Architecture: The Improved Strategy for Good E-Governance

    Directory of Open Access Journals (Sweden)

    Dr. G. P. Singh Rajendra Singh Thapa

    2011-08-01

    Full Text Available Cloud Computing provides a great opportunity for governments across the globe, to provide reliable E-Governance quickly, at lower costs. Cloud computing features like application virtualization, end-to-end service management, instant deployment and ease of maintenance are catalysts that jumpstart application deployment on the Cloud. With proper planning, execution, training and good management, the Cloud infrastructure can greatly reduce overall costs for government departments maintaining and managing E-Services for E-Governance, and help in efficiently utilization.

  10. Social Smart City: Introducing Digital and Social Strategies for Participatory Governance in Smart Cities

    NARCIS (Netherlands)

    Effing, Robin; Groot, Bert P.; Scholl, Hans Jochen; Glassey, Olivier; Janssen, Marijn; Klievink, Bram; Lindgren, Ida; Parycek, Peter; Tambouris, Efthimios; Wimmer, Maria A.; Janowski, Tomasz; Soares, Sa Delfina

    2016-01-01

    Cities increasingly face challenges regarding participatory governance in order to become a “smart city”. The world’s best cities to live in are not the ones with the most advanced technological layers but cities that create an atmosphere where citizens, companies and government together build a vit

  11. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL

    DEFF Research Database (Denmark)

    Baraniskin, Alexander; Birkenkamp-Demtröder, Karin; Maghnouj, Abdelouahid;

    2012-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are involved in different biological processes by suppressing target gene expression. Altered expression of miR-30a-5p has been reported in colon carcinoma. To elucidate its potential biological role in colon cancer, miR-30a-5p was overexpressed via...... were screened for DTL expression and DTL was found to be overexpressed in 95.8% of human colorectal cancers compared with normal colon mucosa. In conclusion, our data identified miR-30a-5p as a tumor-suppressing miRNA in colon cancer cells exerting its function via modulation of DTL expression, which...... is frequently overexpressed in colorectal cancer. Thus, our data suggest that restoring miR-30a-5p function may prove useful as therapeutic strategy for tumors with reduced miR-30a-5p expression....

  12. Teacher Professional Development Strategies in Australian Government and Professional Associations Documents

    Directory of Open Access Journals (Sweden)

    Kostina Ludmyla

    2015-03-01

    Full Text Available Teacher in Australia is determined as an active participant of professional community with high level of collaboration, professional development coherent activities and collaborative learning practice. Thus, teacher quality is one of critical factors affecting student outcomes. The article touches upon the issue of the potential to improve secondary school teacher professional expertise in Australia. These are initiatives approved by Australian specific organizations at government and non-government levels. The author describes the goals and directions of secondary school teacher government support and government strong requirements for teacher professional learning. The article also considers the role of Australian professional education organizations in teacher professional growth. The analysis of the goals is carried out by means of government and professional education organizations documents. The author reports that social context of secondary school teacher professional development in Australia is provided through government education institutions. In support of this fact there is a range of government projects, programmes and documents approved at international and national levels and aimed to encourage lifelong quality teacher development. Furthermore, teacher professional development support is also organized by various Australian professional associations that work collaboratively. Moreover, these associations are not only focused on teacher professional development national standards, requirements and forms but global trends in professional learning and performance.

  13. 卫生部门治理:战略与机制%Health sector governance:Strategies and mechanisms

    Institute of Scientific and Technical Information of China (English)

    刘丽杭

    2014-01-01

    在将健康作为一个要素融入所有政府部门与社会团体政策制定中的大健康整合战略下,政府各部门及社会团体在共识基础上形成广泛性治理目标,由政府主导卫生系统的运行,通过加强政府各部门间及与社会组织的协调与合作,统筹卫生系统的服务及管理功能,建立社会参与的绩效问责机制,实现提升卫生部门治理水平,改善社会健康结果的目标。%Under the health integration strategies of public policy to health in all policies of all sectors and so-cial areas, government departments and social organizations form a broad consensus on the basis of the goals of gov-ernance, led by government health system operations, through the strengthening of coordination and cooperation a-mong government departments and social organizations as well as overall planning of the service functions of the health system, and the establishment of community participation in the performance accountability mechanism, in order to enhance the level of health sector governance and improve community health outcomes.

  14. Survival Strategies and Sustainability of Small and Medium Enterprises in the Oshodi-Isolo Local Government Area of Lagos State

    Directory of Open Access Journals (Sweden)

    Ifekwem Nkiruka

    2016-12-01

    Full Text Available Small and medium enterprises (SMEs play an essential role in the sustainable development of countries. They help in employment generation, industrial production increase, and export, social enrichment as well as political stability. This study investigates the survival strategies and sustainability of SMEs using selected small businesses in the Oshodi-Isolo Local Government Area, Lagos State. It examines the type of growth strategies that SMEs adopt, ascertains what influences their survival strategies as well as the challenges that hinder their growth. Fifty (50 SMEs were randomly sampled. Their owners and managers were interviewed using questionnaires. Data collected were analysed using descriptive statistics and Pearson product–moment correlation coefficient statistics. Our findings reveal that there is a statistically significant relationship between survival strategies and SMEs’ sustainability. The major implication of the findings is that maintaining small but committed and motivated employees is critical in guaranteeing the survival of the SMEs in a volatile economy. The study recommends that there be a need for orientation and educational programmes to change the mindset of business owners to enable them to graduate from sole atomistic proprietor devoid of modern scientific business practice and effective succession to corporate status with an apparatus of modern business management practices and corporate vision. Finally, the study further suggests some imperatives for policy makers concerned with promoting small businesses’ growth and sustainability in the Oshodi-Isolo Local Government Area of Lagos State.

  15. Accidental versus operational oil spills from shipping in the Baltic Sea: risk governance and management strategies.

    Science.gov (United States)

    Hassler, Björn

    2011-03-01

    Marine governance of oil transportation is complex. Due to difficulties in effectively monitoring procedures on vessels en voyage, incentives to save costs by not following established regulations on issues such as cleaning of tanks, crew size, and safe navigation may be substantial. The issue of problem structure is placed in focus, that is, to what degree the specific characteristics and complexity of intentional versus accidental oil spill risks affect institutional responses. It is shown that whereas the risk of accidental oil spills primarily has been met by technical requirements on the vessels in combination with Port State control, attempts have been made to curb intentional pollution by for example increased surveillance and smart governance mechanisms such as the No-Special-Fee system. It is suggested that environmental safety could be improved by increased use of smart governance mechanisms tightly adapted to key actors' incentives to alter behavior in preferable directions.

  16. Adaptation strategies to pasture degradation:Gap between government and local nomads in the eastern Tibetan Plateau

    Institute of Scientific and Technical Information of China (English)

    YAN Jianzhong; WU Yingying; ZHANG Yili

    2011-01-01

    In the last decade,there has been increasing interest in climate change,pasture degradation and its driving forces,and innovations in nomadic pastoralism on the Tibetan Plateau.However,little is known of indigenous strategies of adaptation to pasture degradation,which limits the effectiveness of adaptation strategies planned by local government.This paper analyzes nomads' strategies of adaptation to pasture degradation on the basis of a field survey of three townships of Dalag County in the source regions of the Yangtze and Yellow rivers.Pastures there have evidently degraded,with pastures in Wasai mainly in a state of slight or medium degradation and those in Manzhang and Jianshe in a state of medium or severe degradation.With the degradation of pasture,the grazing time is reduced,which affects the livelihoods of nomads.Although the Four-Package Project has commenced in this region,there is still severe fodder shortage in winter and spring.The traditional hay storage strategy does not work because of pasture degradation,and few nomads establish fenced and artificial pastures.Therefore,nomads have employed other strategies,such as renting pasture,providing supplementary feed,and diversifying their livelihoods.Local strategies taken by nomads can provide valuable insights into ecological restoration and livelihood improvement in the region and suggest changes to means promoted by local government.It is necessary to seek new means that combine the best aspects of nomadic pastoralism with modern stockbreeding technologies to help nomads adapt to pasture degeneration and improve their livelihoods.

  17. Governance structure and transaction cost: relationship between strategy and asset specificity

    Directory of Open Access Journals (Sweden)

    Christian Luiz da Silva

    2009-06-01

    Full Text Available This article presents a theoretical discussion of the determining factors of governance structures, using the transaction cost approach. The coexistence of distinct structures in the same production chain, whose assets show no difference in terms of specificity, is a problematic challenge for transaction cost economics, since it predicts a convergence towards the most efficient structures. The research is pure and explanatory and seeks to identify the determining or contributing variables to the occurrence of the phenomena. Thus, the research source is documental, encompassing the literature discussing the relation between governance structure and transaction cost.

  18. Governance structure and transaction cost: relationship between strategy and asset specificity

    Directory of Open Access Journals (Sweden)

    Christian Luiz da Silva

    2007-12-01

    Full Text Available This article presents a theoretical discussion of the determining factors of governance structures, using the transaction cost approach. The coexistence of distinct structures in the same production chain, whose assets show no difference in terms of specificity, is a problematic challenge for transaction cost economics, since it predicts a convergence towards the most efficient structures. The research is pure and explanatory and seeks to identify the determining or contributing variables to the occurrence of the phenomena. Thus, the research source is documental, encompassing the literature discussing the relation between governance structure and transaction cost.

  19. Poverty in Mexico : An Assessment of Conditions, Trends and Government Strategy

    OpenAIRE

    Walton, Michael; Lopez-Acevedo, Gladys

    2005-01-01

    In 2002, half of Mexico's population lived in poverty and one fifth in extreme poverty, slightly lower than before the 1994-1995 crisis. Mexico has made major progress in some poverty dimensions -health, nutrition and education outcomes, access to basic health and education services, electricity, water and (to a lesser extent) sanitation. Large increases in government spending enabled key ...

  20. From Governing through Data to Governmentality through Data: Artefacts, Strategies and the Digital Turn

    Science.gov (United States)

    Souto-Otero, Manuel; Beneito-Montagut, Roser

    2016-01-01

    The article argues that current discussions about governance through data in education can be fruitfully extended through: (1) the establishment of connections with wider debates about the role of commensuration processes and governmentality in the recreation of education systems; (2) greater emphasis on the "artefacts" through which…

  1. How has government policy post-Global Strategy for Plant Conservation impacted on science? The Ethiopian perspective.

    Science.gov (United States)

    Demissew, Sebsebe

    2011-01-01

    In this paper, existing relevant Ethiopian government biodiversity-related policies and strategies, and mandates of various institutions prior to GSPC targets, are reviewed. Response to whether or not institutions responded to GSPC targets as the result of new policies or rebranded their work to fit within the context of existing policies and adjust their outcomes to fit into the GSPC targets is provided. The Ethiopian national report of 2009 submitted to the Convention of Biological Diversity Secretariat is reviewed and gaps analysed. The policies of the Federal government (and implementing institutions) post-GSPC so far have had only a limited impact on science, but research institutions have aligned their outputs to fit with the GSPC targets. Suggestions, conclusions and recommendations are made in order to work effectively towards the realization of the GSPC targets beyond 2010 in Ethiopia.

  2. Sustainability · Strategy · Space – exploring influences on governing for urban sustainability in municipalities

    OpenAIRE

    Fenton, Paul

    2016-01-01

    The pursuit of urban sustainability is considered central to sustainable development and is a key objective of the global Sustainable Development Goals (2015) and the New Urban Agenda (2016). This thesis aims to contribute to debates on urban sustainability by providing insights as to the role of actors participating in processes of governing for urban sustainability, with particular focus on the municipal organisation. The thesis employs an interdisciplinary approach to illustrate divergent ...

  3. Energy efficiency: implemented strategies in the new building for regional Government Offices in Mérida (Spain)

    OpenAIRE

    Fairbanks, Bruce S.; Montero, Eduardo

    2007-01-01

    The architecture office GOP was awarded the execution of the project for the regional government office building “Consejerías”) in the city of Mérida, designed by Bruce S. Fairbanks, through an International Competition of Ideas summoned by the Junta de Extremadura. The new Consejerías in Mérida set the standards for a wholly sustainable building. It modifies its natural outdoors environment by soothing the climate and giving shelter. A design strategy was, among others, to gain as much conf...

  4. The moderating role of competitive strategy in relating frim performance to quality management and government support

    NARCIS (Netherlands)

    Han, J.; Omta, S.W.F.; Trienekens, J.H.; Kemp, R.G.M.

    2010-01-01

    One of the main concerns in companies is quality management and its relationship to firm performance. Recently a growing interest in research is the important role of the business environment in the competitive strategy choices of companies. By proposing a conceptual framework for a general model th

  5. Governance Strengths and Weaknesses to implement the Marine Strategy Framework Directive in European Waters

    DEFF Research Database (Denmark)

    Freire-Gibb, L. Carlos; Koss, Rebecca; Piotr, Margonski

    2014-01-01

    The ambitious Marine Strategy Framework Directive (MSFD) has been the focus of much marine research across Europe in the pursuit of achieving Good Environmental Status in the four European Union marine regions; Baltic Sea, Black Sea, Mediterranean Sea and North-east Atlantic. This research addres...

  6. Recurrent Governance Challenges in the Implementation and Alignment of Flood Risk Management Strategies: a Review

    NARCIS (Netherlands)

    Dieperink, C.; Hegger, D.L.T.; Bakker, M.H.N.; Kundzewicz, Zbigniew W.; Green, Colin; Driessen, P.P.J.

    2016-01-01

    In Europe increasing flood risks challenge societies to diversify their Flood Risk Management Strategies (FRMSs). Such a diversification implies that actors not only focus on flood defence, but also and simultaneously on flood risk prevention, mitigation, preparation and recovery. There is much lite

  7. TETRASOMY-5P MOSAICISM IN A BOY WITH DELAYED GROWTH, HYPOTONIA, MINOR ANOMALIES, AND AN ADDITIONAL ISOCHROMOSOME-5P [46,XY/47,XY,+I(5P)

    NARCIS (Netherlands)

    SIJMONS, RH; LEEGTE, B; VANLINGEN, RA; DEPATER, JM; VANDERVEEN, AY; DELCANHO, H; TENKATE, LP; BREED, ASPM

    1993-01-01

    We describe a 1-year-old boy with a rare de novo 46,XY/47,XY,+ i(5p) mosaicism (ratios 28/3 in peripheral blood lymphocytes and 2/12 in skin fibroblasts). The boy, born after a pregnancy of 34 weeks, had lung hypoplasia, persistent hypotonia, and postnatal growth failure. Craniofacial anomalies were

  8. Examining Why the Canadian Federal Government Placed an Orphan Drug Strategy on Their Decision Agenda Now

    Directory of Open Access Journals (Sweden)

    Mark Gary Embrett

    2014-02-01

    Full Text Available The Ministry of Health’s announcement of a National Orphan Drug Framework on 3 October 2012 was the first federal public acknowledgement of orphan drugs since the 1997 Drugs Directorate (DD policy statement. The reform primarily announced an Orphan Drug Policy for Canada. This paper explains why the government decided to make this announcement now. Media and Parliamentary documents were analyzed for their use of symbols, numbers, and language in causal stories told by political actors. The initial story was that Canada’s population was too small and the cost too high for an orphan drug policy. Over the next fifteen years, a powerful interest group, the Canadian Organization for Rare Disorders (CORD, mobilized the rare disease community into a cooperative effort that generated collective action. They redefined the DD story from one of natural causes, to inadvertence, and finally to intentional causation. Their story invoked a federal response because it blamed the government directly for not acting on behalf of the 3 million Canadians with rare diseases, when patients in other countries were receiving better care.

  9. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL.

    Science.gov (United States)

    Baraniskin, Alexander; Birkenkamp-Demtroder, Karin; Maghnouj, Abdelouahid; Zöllner, Hannah; Munding, Johanna; Klein-Scory, Susanne; Reinacher-Schick, Anke; Schwarte-Waldhoff, Irmgard; Schmiegel, Wolff; Hahn, Stephan A

    2012-04-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are involved in different biological processes by suppressing target gene expression. Altered expression of miR-30a-5p has been reported in colon carcinoma. To elucidate its potential biological role in colon cancer, miR-30a-5p was overexpressed via a lentiviral vector system in two different colon cancer cell lines. This induced in both lines miR-30a-5p-mediated growth inhibition, attributable to a cell cycle arrest at the G(1) phase and an induction of apoptosis. Combining global gene expression analyses of miR-30a-5p transgenic line HCT116 with in silico miRNA target prediction, we identified the denticleless protein homolog (DTL) as a potential miRNA-30a-5p target. Subsequent reporter gene assays confirmed the predicted miR-30a-5p binding site in the 3'untranslated region of DTL. Importantly, overexpression of DTL in HCT116 cells partially rescued these cells from miR-30a-5p-mediated growth suppression. In addition, TP53 and CDKN1A expression were increased in miR-30a-5p-overexpressing HCT116 cells, suggesting that miR-30a-5p is able to modulate the cell cycle via a DTL-TP53-CDKN1A regulatory circuit. Finally, 379 colorectal cancer tissues were screened for DTL expression and DTL was found to be overexpressed in 95.8% of human colorectal cancers compared with normal colon mucosa. In conclusion, our data identified miR-30a-5p as a tumor-suppressing miRNA in colon cancer cells exerting its function via modulation of DTL expression, which is frequently overexpressed in colorectal cancer. Thus, our data suggest that restoring miR-30a-5p function may prove useful as therapeutic strategy for tumors with reduced miR-30a-5p expression.

  10. Developing knowledge and strategies for enabling and governing transitions to a low carbon society

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Jørgensen, Ulrik; Lauridsen, Erik Hagelskjær

    Most of the research on low carbon society in Denmark has hitherto focused on developing scenarios and analyzing possible policy instruments, including market mechanisms, costs and impacts in relation to known options and impacts. The Danish Council of Strategic Research funds the four year......, companies, cities, and national and international policy. Theoretically the research alliance builds upon a combination of theories including social practice theory, innovation economy, institutional theory, actor-network theory and governance theory. Through a combination of historical analysis, case...... stakeholders to make continuous adjustments of objectives and means in unavoidably conflict ridden transition processes.  Analyses of how key measures and institutions at different societal levels might contribute to transition processes.  Characterisation of 4-6 typical sustainable transition set...

  11. A Blueprint for Florida's Clean Energy Future - Case Study of a Regional Government's Environmental Strategy

    Directory of Open Access Journals (Sweden)

    Margaret Lowman

    2009-04-01

    Full Text Available On 13 July 2007, Governor Charlie Crist of Florida signed executive orders to establish greenhouse gas emission targets that required an 80 percent reduction below 1990 levels by the year 2050. Florida is a very high-risk state with regard to climate change. Its 1,350-mile-long coastline, location in "Hurricane Alley," reliance on coral reefs and other vulnerable natural resources for its economy, and the predictions that state population could double in the next 30 years all contribute to this designation of "high-risk. As a consequence of the potential economic and ecological impacts of climate change to Florida, a series of Action Teams were created to plan for adaptation to impending environmental changes. As the 26th largest emitter of carbon dioxide on a global scale, Florida needs to act aggressively to create a clean energy footprint as part of its statewide initiatives but with global impacts. This case study examines the process and expected outcomes undertaken by a regional government that anticipates the need for stringent adaptation.

  12. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis

    Science.gov (United States)

    Averette, Anna F.; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E.

    2016-01-01

    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  13. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  14. The PP1 binding code: a molecular-lego strategy that governs specificity.

    Science.gov (United States)

    Heroes, Ewald; Lesage, Bart; Görnemann, Janina; Beullens, Monique; Van Meervelt, Luc; Bollen, Mathieu

    2013-01-01

    Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates. PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells. The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1. Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites. This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties. The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic. PIPs control associated PP1 by interference with substrate recruitment or access to the active site. In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1. The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo.

  15. Evidence for xylitol 5-P production in human dental plaque

    Energy Technology Data Exchange (ETDEWEB)

    Waaler, S.M. (Department of Preclinical Techniques and Material Sciences and Department of Pedodontics, Dental Faculty, University of Oslo, Oslo (Norway))

    1992-01-01

    The Turku sugar studies indicated that xylitol may possess a caries-therapeutic effect. More recent data show that xylotol exhibits a bacteriostatic activity on a wide range of bacteria based on uptake and expulsion of xylitol. Intracellular xylitol 5-P appears to be a key substance associated with inhibition of bacterial metabolism by xylitol. This has been shown in studies with pure strains of bacteria, mainly Streptococcus mutans. The aim of the present study was to examine if production of xylitol 5-P occurs in freshly collected dental plaque which is exposed to labeled xylitol. Plaque extracts were analyzed by thin-layer chromatography combined with autoradiography and high performance liquid chromatography. Strong indications were obtained that xylitol 5-P is readily produced by dental plaque. No other significant xylitol metabolites were identified. The bacteriostatic properties of xylitol in plaque are a mechanism which may well account for the caries-therapeutic effect of xylitol. (au).

  16. The globalisation strategies of five Asian tobacco companies: a comparative analysis and implications for global health governance.

    Science.gov (United States)

    Lee, Kelley; Eckhardt, Jappe

    2017-03-01

    The global tobacco industry, from the 1960s to mid 1990s, saw consolidation and eventual domination by a small number of transnational tobacco companies (TTC). This paper draws together comparative analysis of five case studies in the special issue on 'The Emergence of Asian Tobacco Companies: Implications for Global Health Governance.' The cases suggest that tobacco industry globalisation is undergoing a new phase, beginning in the late 1990s, with the adoption of global business strategies by five Asian companies. The strategies were prompted foremost by external factors, notably market liberalisation, competition from TTCs and declining domestic markets. State protection and promotion enabled the industries in Japan, South Korea and China to rationalise their operations ahead of foreign market expansion. The TTM and TTL will likely remain domestic or perhaps regional companies, JTI and KT&G have achieved TTC status, and the CNTC is poised to dwarf all existing companies. This global expansion of Asian tobacco companies will increase competition which, in turn, will intensify marketing, exert downward price pressures along the global value chain, and encourage product innovation. Global tobacco control requires fuller understanding of these emerging changes and the regulatory challenges posed by ongoing globalisation.

  17. 开放政府与政府数据公开战略%Open Government and Government Data Disclosure Strategy

    Institute of Scientific and Technical Information of China (English)

    周和

    2012-01-01

    提高政府公信力是全球关注的问题,创新政府管理,建设透明与开放政府,更多地在公共事务上实行公民参与,已成为全球的发展趋势。各国政府也在努力寻找各种途径,使政府更加透明、回应性更强、更加负责和有效。这也使得美国“开放政府”行动的影响越来越大。透明度、参与和协作这三项原则,构成开放政府的基石。而合理地开放政府信息、扩大信息公开与敏感信息的保护、提高政府信息的可及性则是有效实施政府数据公开战略,建设开放政府的必然选择。%This paper describes the origin of open government, and discusses the connotation, value and trends of open government, and points out that innovative government management, building transparent and open government has become the development trend of the world. At the same time, this paper analyzes discussion of the Chinese scholars on building open government in China, and conducts specific discussion from three aspects: reali- zing greater disclosure of government data, finding a balance between open government and sensitive information protection, as well as facilitating public access to government information.

  18. miR-199a-5p regulates β1 integrin through Ets-1 to suppress invasion in breast cancer.

    Science.gov (United States)

    Li, Wentong; Wang, Hui; Zhang, Jinbao; Zhai, Limin; Chen, Weijuan; Zhao, Chunling

    2016-07-01

    Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of β1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of β1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.

  19. Interstitial deletion 5p accompanied by dicentric ring formation of the deleted segment resulting in trisomy 5p13-cen

    Energy Technology Data Exchange (ETDEWEB)

    Schuffenhauer, S.; Daumer-Haas, C.; Murken, J. [Ludwig-Maximilians-Universitaet Muenchen (Germany)] [and others

    1996-10-02

    Karyotypes with an interstitial deletion and a marker chromosome formed from the deleted segment are rare. We identified such a rearrangement in a newborn infant, who presented with macrocephaly, asymmetric square skull, minor facial anomalies, omphalocele, inguinal hernias, hypospadias, and club feet. The karyotype 46,XY,del(5)(pter{r_arrow}p13::cen{r_arrow}qter)/47,XY,+dicr(5)(:p13{r_arrow}cen::p13{r_arrow}cen),del(5)(pter{r_arrow}p13::cen{r_arrow}qter) was identified by banding studies and FISH analysis in the peripheral lymphocytes. One breakpoint on the del(5) maps distal to GDNF, and FISH analysis using an {alpha}-satellite probe suggests that the proximal breakpoint maps within the centromere. The dicentric r(5) consists of two copies of the segment deleted in the del(5), resulting in trisomy of proximal 5p (5p13-cen). The phenotype of the propositus is compared with other trisomy 5p cases and possible mechanisms for the generation of this unique chromosomal rearrangement are discussed. 27 refs., 3 figs.

  20. D1-D5-P microstates at the cap

    CERN Document Server

    Giusto, Stefano; Mathur, Samir D; Turton, David

    2012-01-01

    The geometries describing D1-D5-P bound states in string theory have three regions: flat asymptotics, an anti-de Sitter throat, and a 'cap' region at the bottom of the throat. We identify the CFT description of a known class of supersymmetric D1-D5-P microstate geometries which describe degrees of freedom in the cap region. The class includes both regular solutions and solutions with conical defects, and generalizes configurations with known CFT descriptions: a parameter related to spectral flow in the CFT is generalized from integer to fractional values. We provide strong evidence for this identification by comparing the massless scalar excitation spectrum between gravity and CFT and finding exact agreement.

  1. New D1-D5-P geometries from string amplitudes

    CERN Document Server

    Giusto, Stefano; Turton, David

    2011-01-01

    We derive the long range supergravity fields sourced by a D1-D5-P bound state from disk amplitudes for massless closed string emission. We suggest that since the parameter controlling the string perturbation expansion for this calculation decreases with distance from the bound state, the resulting asymptotic fields are valid even in the regime of parameters in which there is a classical black hole solution with the same charges. The supergravity fields differ from the black hole solution by multipole moments and are more general than those contained within known classes of solutions in the literature, whilst still preserving four supersymmetries. Our results support the conjecture that the black hole solution should be interpreted as a coarse-grained description rather than an exact description of the gravitational field sourced by D1-D5-P bound states in this regime of parameters.

  2. Energy Efficiency Programs in K-12 Schools: A Guide to Developing and Implementing Greenhouse Gas Reduction Programs. Local Government Climate and Energy Strategy Series

    Science.gov (United States)

    US Environmental Protection Agency, 2011

    2011-01-01

    Saving energy through energy efficiency improvements can cost less than generating, transmitting, and distributing energy from power plants, and provides multiple economic and environmental benefits. Local governments can promote energy efficiency in their jurisdictions by developing and implementing strategies that improve the efficiency of…

  3. Detection of rare reassortant G5P[6] rotavirus, Bulgaria.

    Science.gov (United States)

    Mladenova, Zornitsa; Papp, Hajnalka; Lengyel, György; Kisfali, Péter; Steyer, Andrej; Steyer, Adela F; Esona, Mathew D; Iturriza-Gómara, Miren; Bányai, Krisztián

    2012-12-01

    During the ongoing rotavirus strain surveillance program conducted in Bulgaria, an unusual human rotavirus A (RVA) strain, RVA/Human/BG/BG620/2008/G5P[6], was identified among 2200 genotyped Bulgarian RVAs. This strain showed the following genomic configuration: G5-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analysis of the genes encoding the neutralization proteins and backbone genes identified a probable mixture of RVA genes of human and porcine origin. The VP1, VP6 and NSP2 genes were more closely related to typical human rotavirus strains. The remaining eight genes were either closely related to typical porcine and unusual human-porcine reassortant rotavirus strains or were equally distant from reference human and porcine strains. This study is the first to report an unusual rotavirus isolate with G5P[6] genotype in Europe which has most likely emerged from zoonotic transmission. The absence of porcine rotavirus sequence data from this area did not permit to assess if the suspected ancestral zoonotic porcine strain already had human rotavirus genes in its genome when transmitted from pig to human, or, the transmission was coupled or followed by gene reassortment event(s). Because our strain shared no neutralization antigens with rotavirus vaccines used for routine immunization in children, attention is needed to monitor if this G-P combination will be able to emerge in human populations. A better understanding of the ecology of rotavirus zoonoses requires simultaneous monitoring of rotavirus strains in humans and animals.

  4. Cost effectiveness of a government supported policy strategy to decrease sodium intake: global analysis across 183 nations

    Science.gov (United States)

    Webb, Michael; Fahimi, Saman; Singh, Gitanjali M; Khatibzadeh, Shahab; Micha, Renata; Powles, John

    2017-01-01

    was best in South Asia (I$116/DALY); across the world’s 30 most populous countries, best in Uzbekistan (I$26.08/DALY) and Myanmar (I$33.30/DALY). Cost effectiveness was lowest in Australia/New Zealand (I$880/DALY, or 0.02×gross domestic product (GDP) per capita), although still substantially better than standard thresholds for cost effective (<3.0×GDP per capita) or highly cost effective (<1.0×GDP per capita) interventions. Most (96.0%) of the world’s adult population lived in countries in which this intervention had a cost effectiveness ratio <0.1×GDP per capita, and 99.6% in countries with a cost effectiveness ratio <1.0×GDP per capita. Conclusion A government “soft regulation” strategy combining targeted industry agreements and public education to reduce dietary sodium is projected to be highly cost effective worldwide, even without accounting for potential healthcare savings. PMID:28073749

  5. MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2

    Directory of Open Access Journals (Sweden)

    Qin X

    2015-12-01

    .Conclusion: The molecular pathway of miR-125a-5p/ABL2 plays an important role in human cervical carcinoma. Targeting miR-125a-5p/ABL2 pathway may provide a new treatment strategy for patients with cervical carcinoma. Keywords: cervical carcinoma, miR-125a-5p, ABL2, cancer proliferation, cancer migration

  6. Public reaction to the UK government strategy on childhood obesity in England: A qualitative and quantitative summary of online reaction to media reports.

    Science.gov (United States)

    Gregg, Rebecca; Patel, Ajay; Patel, Sumaiya; O'Connor, Laura

    2017-02-20

    This work aimed to summarise public real-time reaction to the publication of the UK government childhood obesity strategy by applying a novel research design method. We used a netnographic technique to carry out thematic analysis of user-generated comments to online newspaper articles related to the strategy. We examined likes/dislikes associated with comments as a proxy of agreement of the wider community with identified themes. To examine media influence on the comments we carried out thematic analysis of online media headlines published about the strategy, and compared these themes with themes identified from comments. Three newspaper articles and 1704 associated comments were included. Three parent themes were identified: paternalism/libertarianism, lobbyist influence and, anecdotal solutions. The comments were largely negative (94%). Commenters were split as to individual responsibilities and the role of the government, some felt that lobbyist influence had won out over the nation's health and others offered non-evidence based solutions. The ten most liked and disliked comments reflected themes identified in our main analysis. There was parity between themes that emerged from comments and from headlines. This summary of public reaction to the obesity strategy publication may aid translation of public views and receptiveness into practice and inform subsequent government action and policy. Furthermore, the process applied herein may provide a means of informal public engagement.

  7. Rethinking the Changing Structures of Rural Local Government--State Power, Rural Politics and Local Political Strategies?

    Science.gov (United States)

    Pemberton, Simon; Goodwin, Mark

    2010-01-01

    There is a notable absence in contemporary rural studies--of both a theoretical and empirical nature--concerning the changing nature of rural local government. Despite the scale and significance of successive rounds of local government reorganisation in the UK, very little has been written on this topic from a rural perspective. Instead research…

  8. GPC1 Regulated by miR-96-5p, Rather than miR-182-5p, in Inhibition of Pancreatic Carcinoma Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Chunlong Li

    2014-04-01

    Full Text Available To determine the relationships between miR-96-5p/-182-5p and GPC1 in pancreatic cancer (PC, we conducted the population and in vitro studies. We followed 38 pancreatic cancer patients, measured and compared the expression of miR-96-5p/-182-5p, GPC1, characteristics and patients’ survival time of different miR-96-5p/-182-5p expression levels in PC tissues. In an in vitro study, we investigated the proliferation, cycle and apotosis in cells transfected with mimics/inhibitors of the two miRNAs, and determine their effects on GPC1 by dual-luciferase assay. In the follow-up study, we found that the expressions of miR-96-5p/-182-5p were lower/higher in PC tissues; patients with lower/higher levels of miR-96-5p/-182-5p suffered poorer characteristics and decreased survival time. In the in vitro study, the expressions of miR-96-5p/-182-5p were different in cells. Proliferation of cells transfected with miR-96-5p mimics/inhibitors was lower/higher in Panc-1/BxPC-3; when transfected with miR-182-5p mimics/inhibitors, proliferation of cells were higher/lower in AsPC-1/Panc-1. In a cell cycle study, panc-1 cells transfected with miR-96-5p mimics was arrested at G0/G1; BxPC-3 cells transfected with miR-96-5p inhibitors showed a significantly decrease at G0/G1; AsPC-1 cells transfected with miR-182-5p mimics was arrested at S; Panc-1 cells transfected with miR-182-5p inhibitors showed a decrease at S. MiR-96-5p mimics increased the apoptosis rate in Panc-1 cells, and its inhibitors decreased the apoptosis rate in BxPC-3. Dual luciferase assay revealed that GPC1 was regulated by miR-96-5p, not -182-5p. We found that miR-96-5p/-182-5p as good markers for PC; miR-96-5p, rather than -182-5p, inhibits GPC1 to suppress proliferation of PC cells.

  9. Inhibition of microRNA-31-5p protects human colonic epithelial cells against ionizing radiation

    Science.gov (United States)

    Kim, Sang Bum; Zhang, Lu; Barron, Summer; Shay, Jerry W.

    2014-04-01

    MicroRNAs (miRNAs), endogenous non-coding small RNAs, are sensitive to environmental changes, and their differential expression is important for adaptation to the environment. However, application of miRNAs as a clinical prognostic or diagnostic tool remains unproven. In this study we demonstrate a chronic/persistent change of miRNAs from the plasma of a colorectal cancer susceptible mouse model (CPC;Apc) about 250 days after exposure to a simulated solar particle event (SPE). Differentially expressed miRNAs were identified compared to unirradiated control mice, including miR-31-5p, which we investigated further. To address the cellular function of miR-31-5p, we transfected a miR-31-5p mimic (sense) or inhibitor (antisense) into immortalized human colonic epithelial cells followed by gamma-irradiation. A miR-31-5p mimic sensitized but a miR-31-5p inhibitor protected colonic epithelial cells against radiation induced killing. We found that the miR-31-5p mimic inhibited the induction of hMLH1 expression after irradiation, whereas the miR-31-5p inhibitor increased the basal level of hMLH1 expression. The miR-31-5p inhibitor failed to modulate radiosensitivity in an hMLH1-deficient HCT116 colon cancer cell line but protected HCT116 3-6 and DLD-1 (both hMLH1-positive) colon cancer cell lines. Our findings demonstrate that miR-31-5p has an important role in radiation responses through regulation of hMLH1 expression. Targeting this pathway could be a promising therapeutic strategy for future personalized anti-cancer radiotherapy.

  10. Stepping up the pace : SDC summary response to the UK Shared Framework for Sustainable Development and UK Government Sustainable Development Strategy 2005

    OpenAIRE

    2005-01-01

    English language version of 'Gwneud cynnydd yn gyflymach : ymateb cryno’r Comisiwn Datblygu Cynaliadwy i Fframwaith Cyffredin y DU ar gyfer Datblygu Cynaliadwy a Strategaeth Datblygu Cynaliadwy Llywodraeth y DU ar gyfer 2005'. In this summary we provide an overview of the UK’s 'Shared Framework for Sustainable Development' and a quick take on where we think the strengths of the UK Government strategy lie, where we see key challenges ahead, and the areas where we want to see the Governme...

  11. Ca(2+) induces PI(4,5)P2 clusters on lipid bilayers at physiological PI(4,5)P2 and Ca(2+) concentrations.

    Science.gov (United States)

    Sarmento, Maria J; Coutinho, Ana; Fedorov, Aleksander; Prieto, Manuel; Fernandes, Fabio

    2014-03-01

    Calcium has been shown to induce clustering of PI(4,5)P2 at high and non-physiological concentrations of both the divalent ion and the phosphatidylinositol, or on supported lipid monolayers. In lipid bilayers at physiological conditions, clusters are not detected through microscopic techniques. Here, we aimed to determine through spectroscopic methodologies if calcium plays a role in PI(4,5)P2 lateral distribution on lipid bilayers under physiological conditions. Using several different approaches which included information on fluorescence quantum yield, polarization, spectra and diffusion properties of a fluorescent derivative of PI(4,5)P2 (TopFluor(TF)-PI(4,5)P2), we show that Ca(2+) promotes PI(4,5)P2 clustering in lipid bilayers at physiological concentrations of both Ca(2+) and PI(4,5)P2. Fluorescence depolarization data of TF-PI(4,5)P2 in the presence of calcium suggests that under physiological concentrations of PI(4,5)P2 and calcium, the average cluster size comprises ~15 PI(4,5)P2 molecules. The presence of Ca(2+)-induced PI(4,5)P2 clusters is supported by FCS data. Additionally, calcium mediated PI(4,5)P2 clustering was more pronounced in liquid ordered (lo) membranes, and the PI(4,5)P2-Ca(2+) clusters presented an increased affinity for lo domains. In this way, PI(4,5)P2 could function as a lipid calcium sensor and the increased efficiency of calcium-mediated PI(4,5)P2 clustering on lo domains might provide targeted nucleation sites for PI(4,5)P2 clusters upon calcium stimulus.

  12. Stakeholder Governance

    DEFF Research Database (Denmark)

    Flak, Leif Skiftenes; Rose, Jeremy

    2005-01-01

    The e-government field, like most young fields, lacks a strong body of well-developed theory. One strategy for coping with theoretical immaturity is to import and adapt theories from other, more mature fields. This study reviews Stakeholder Theory (ST) and investigates its potential in relation...... to e-Government. Originally a management theory, stakeholder theory advocates addressing the concerns of all stakeholders in a firm, as opposed to concentration on the interests of senior managers and stockholders. Apart from the original profit focus, there is no serious conceptual mismatch between...... stakeholder theory and government’s objective of providing policy and services for citizens and organizations – society’s stakeholders. Potential problems with adapting a management theory to a government setting are discussed. The paper further discusses how information technology impacts a stakeholder model...

  13. GOVERNANCE AND STRATEGY IMPLEMENTATION IN LOCAL CLUSTERS TO IMPROVE THE PERFORMANCEhttp://dx.doi.org/10.5585/riae.v9i2.1672

    Directory of Open Access Journals (Sweden)

    Helen Fischer Günther

    2010-11-01

    Full Text Available Micro, small and medium enterprises (MSME are designed to operate in networks, cooperatively, in order to obtain benefits that would not occur through the alone action, and encourage the development of local productive arrangements (LPA. Emerge the need for synergy between the actors, operationalized by the mechanisms of integration, which must be managed for efficiency. These characteristics of cooperation and interaction impact the achievement of the objectives and strategies, and administrative functions and plans. Therein appear one of the challenges of present time: how to implement the strategies, plans, and how to make the strategy works? Governance emerges, then, as a medium to achieve the objectives and, so, talk about it in the LPA extends the focus on developing management methods to maintain the idiosyncrasies, to the same extent as they contribute to the effectiveness and improvement in performance.

  14. Food Fraud Prevention: Policy, Strategy, and Decision-Making - Implementation Steps for a Government Agency or Industry.

    Science.gov (United States)

    Spink, John; Fortin, Neal D; Moyer, Douglas C; Miao, Hong; Wu, Yongning

    2016-01-01

    This paper addresses the role of governments, industry, academics, and non-governmental organizations in Food Fraud prevention. Before providing strategic concepts for governments and authorities, definitions of Food Fraud are reviewed and discussed. Next there is a review of Food Fraud activities by the Global Food Safety Initiative (GFSI), the Elliott Review in the United Kingdom, the European Commission resolution on Food Fraud, and the US Food Safety Modernization Act including the Preventative Controls Rule. Two key concepts for governments or a company are: (1) formally, and specifically, mention food fraud as a food issue and (2) create an enterprise-wide Food Fraud prevention plan. The research includes a case study of the implementation of the concepts by a state or provincial agency. This analysis provides a foundation to review the role of science and technology in detection, deterrence and then contributing to prevention.

  15. Review of Ireland’s Road Safety Strategy. On behalf of Department of the Environment and Local Government, Ireland.

    NARCIS (Netherlands)

    Wegman, F.C.M.

    2003-01-01

    SWOV has been requested to carry out a review of Ireland's Road Safety Strategy. This review should pay attention to three aspects: (1) review developments and progress made under the current National Road Safety Strategy 1998-2002; (2) place Ireland's performance in an appropriate international con

  16. How Taxes Can Contribute to The Implementation of The Public Governance Strategy? – An Analysis for Eastern European Countries

    Directory of Open Access Journals (Sweden)

    Vlad Cristina

    2016-09-01

    Full Text Available The paper begins with a short literature review regarding the public governance concept in the EU approach and its methods for establishing a common way to manage different situations for all member states; we discovered that the problems they confront with have to do with good governance and qualitative public administration. In the second part, we developed an econometric model for three Eastern European countries and we found a strong correlation between the total revenues from taxes and social contributions and total gross debt in 2002-2014 period. We ended the paper by emphasizing the conclusions obtained.

  17. 基于网络营销理念提升电子政务影响力的策略研究%The Promotion Strategy of E-government's Impact Based on Network Marketing

    Institute of Scientific and Technical Information of China (English)

    李曼; 包文夏

    2014-01-01

    In the development of e-government,situation government website"heavy construction,light service"affects public access to electronic government information and services.Based on network marketing,his article proposes 4 strategies to promote e-government's impact:SEO strategy,network marketing strategy,viral marketing strategy,customer relationship management strategy.%在电子政务的发展中,政府网站“重建设,轻服务”的现状影响了公众对电子政务信息和服务的获取。基于网络营销理念,提出SEO策略、网络推广策略、病毒营销策略、客户关系管理策略来提升电子政务的影响力。

  18. Public Management Reform and Organizational Performance: An Empirical Assessment of the U.K. Labour Government's Public Service Improvement Strategy

    Science.gov (United States)

    Walker, Richard M.; Boyne, George A.

    2006-01-01

    We present the first empirical assessment of the U.K. Labour government's program of public management reform. This reform program is based on rational planning, devolution and delegation, flexibility and incentives, and enhanced choice. Measures of these variables are tested against external and internal indicators of organizational performance.…

  19. Evaluating farmers’ adaptation strategies to climate change: A case study of Kaou local government area, Tahoua State, Niger Republic

    Directory of Open Access Journals (Sweden)

    A. Moussa Tabbo

    2016-03-01

    Full Text Available The study discusses local farmers’ strategies of coping with and building resilience against the negative impact of climate change. Information for the discussion was from data collected using a set of structured questionnaires from interviews scheduled with 128 farmers. The questionnaire was based on previous literature and direct reconnaissance interview with farmers, which culminated in 13 strategies used for the study being reported. For each question, respondents were asked to choose their best and worst strategies. Thus, the difference between the best and worst strategies consistent with random utility theory has been used for the modelling. Results show that semi-transhumance, various handicrafts making, rural migration, small-scale vegetable production and small-scale river exploitation were the most important strategies identified, whilst water transport and vending, shifting cultivation, gypsum mining, gathering and trading of wild fruits and edible plants as well as cattle and sheep fattening were the least appreciated strategies identified amongst the farmers facing climate change. These findings are therefore imperative for planning farmers’ capacity-building and resilience against climate change projects to ensure sustainability in the study area.Keywords: Farmers’ adaptation strategies; Climate change resilience; Kaou

  20. On Strategies in Translating Metaphor in News of Government Website%政务网新闻中比喻的英译策略研究

    Institute of Scientific and Technical Information of China (English)

    农雪明

    2013-01-01

    Besides the basic features of news, such as timeliness, realness and universality, etc., news of government website should feature with basic characteristics of government website. The use of metaphor could make images vivid and bring much life to Language. But it is not easy to translate metaphors in news of government website. By analyzing some examples of translat-ing metaphors in news of government website, some useful translation strategy will be put forward for universal use.%政务新闻除了具备新闻的时效性、真实性、广泛性等基本特点之外,更重要的是它必须满足政务信息的基本要求与规范。比喻的运用可以使事物生动形象,使语言文采斐然,富有极强的感染力。但在政务新闻比喻的英译过程中要保持语义、修辞的对等却不是一件易事。文章通过分析政务网新闻中比喻英译的例子,研究并提出政务网新闻中比喻的英译策略。

  1. Energy strategy 2050. From coal, oil and gas to green energy; Danish Government's energy policy; Energistrategi 2050 - fra kul, olie og gas til groen energi

    Energy Technology Data Exchange (ETDEWEB)

    2011-02-15

    The Danish Government's ''Energy strategy 2050'' describes how the country can achieve its independence from coal, oil and gas by the year 2050 and significantly reduce its greenhouse gas emissions. The strategy contains a raft of initiatives that will reduce the energy industry's use of fossil fuels by 33 % in 2020, compared with 2009. The reduction will put Denmark well on its way to complete independence of fossil fuels by 2050. The strategy calls for a significant increase in renewable energy obtained from wind, biomass and biogas which over the next decade will increase the share of renewable to 33 % of energy consumption, if the initiatives in the strategy are implemented. The strategy offers an economically responsible path to the conversion of the Danish energy supply, and includes specific initiatives, that are all fully financed and which will not damage the nation's competitiveness. Homeowners will experience moderate increases in the costs of heat and electricity, but will also be given opportunities to lower their energy expenses through greater efficiency. Companies can expect added expenses amounting to 0.1 % of the rise in their gross revenue growth by 2020. (ln)

  2. Management Strategies of Perceived Challenges and Problems of Old People in Ihitte-Uboma Local Government Area of Imo State, Nigeria

    OpenAIRE

    Ojukwu M.O.; S.I. Woko

    2016-01-01

    It has been revealed that over the years, the number of the aged in the world has been on a steady increase. This rising number has great implications for government, researchers, families, youth and the society at large. There is therefore, the proper need for the understanding of the nature problems and challenges as well as the management strategies the aged adopt at this stage of life. The issue of old and preparation for it has been a case of global concern because of the problems associ...

  3. 政府促进合作社发展策略研究%Study on Strategy of Promoting Cooperative Development of Government

    Institute of Scientific and Technical Information of China (English)

    乔为

    2011-01-01

    The weak nature and public welfare of agricultural cooperatives were described,and the government's main strategies to promote cooperative development were analyzed from the legislative,administrative,finance,taxation and education.Finally,on the basis of analysis on the pros and cons of these strategies.it also conluded that the rational choice of government for cooperative development was to develop cooperative education.%阐述了农业合作社的弱质性和公益性,并从立法、行政管理、财政税收和教育方面,分析了政府促进合作社发展的主要策略,最后在分析了这些策略的利弊基础上,提出政府促进合作社发展的理性选择是发展合作社教育。

  4. 地方政府过度举债、风险累积和治理对策%Excessive Issuance, Cumulative Risks and Governance Strategies of Local Government Debt

    Institute of Scientific and Technical Information of China (English)

    方先明; 张谊浩; 蒋或

    2012-01-01

    Recently, China' s local government has been emerging the phenomenon of excessive issuance of local bonds, showing the characteristics of increasingly complicated forms, largescale expansion, significant growth of balance and relatively unbal anced structure. Factors leading to excessive issuance of local bonds include non supporting after tax system reform, appointment and examination system of local officials, inadequate decision making mechanism, not enough law constraints, and so on. Excessive issuance of local bonds, especially the rapid expansion of financing platform of local government, will lead to a variety of risks, and then slow down the development of local economy. This paper discusses about the scientific and operational governance strategies against the excessive issuance of local bonds and its corresponding cumulative risks.%当前我国地方政府出现了过度举债现象,表现出债务形式日趋复杂,规模大幅扩张,余额增速明显,结构相对失衡的特征。地方政府过度举债的原因在于分税制改革后的不配套、地方干部任命与考核制度、决策机制不完善、法制约束力不够等。地方政府过度举债特别是各级地方政府融资平台的迅速扩张势必诱发各种风险,进而阻碍地方经济发展。为此,文章针对地方政府过度举债及其风险累积,提出兼具科学性及可操作性的治理对策。

  5. 信任、治理策略与合资企业社会困境%Trust, Governance Strategies and Social Dilemma of Joint Ventures

    Institute of Scientific and Technical Information of China (English)

    薛晋洁; 史本山

    2016-01-01

    Although joint ventures have become a universally recognized organization form in business activities, it is reported that a considerable part of them dissolve far rapidly than assumed.For joint venture management, a primary challenge is how to settle the social dilemma.Social dilemma management capability directly affects joint ventures′effective operation.Social dilemma of joint ventures embodies the self-interest rational choice of joint venture partners lead to long-term failure of a joint venture. Therefore, it is important for researchers and practitioners to explore the influencing factors and governance strategies of social di-lemma in joint ventures and take advantages of these factors and governance strategies to improve mutual cooperation, decrease partner opportunism and settle social dilemma in Chinese society. Based on the social dilemma theory, transaction cost theory and relational exchange theory, the model of impact of trust on contract governance, relational governance and behavior of joint ventures is established.This paper employs data collected from 242 joint ventures and adopts structure equation model to examine effects of trust on two governance strategies, cooperation and partner opportunism.Meanwhile, trust is divided into two types-high and low level of trust-for investigating how trust as the moderator variable affects trust, two kinds of governance mechanism and joint venture partner′s behavior. The results of structural equation indicate that in a transactional environment of whether high or low level of trust, the influ-ence of trust on relational governance is higher than that of contract governance.Trust has a more positive effect on cooperation when trust is high than that of when trust is low.Similarly, relational governance increases cooperation more when trust is high than that of when trust is low.Unlike the previous results, the influence of contract governance on cooperation is significantly less when trust is high than

  6. Shocks and Coping Strategies of Rural Households: Evidence from Ogo-Oluwa Local Government, Oyo State, Nigeri

    Directory of Open Access Journals (Sweden)

    Seyi Olalekan, Olawuyi

    2011-12-01

    Full Text Available Rural households in Nigeria are vulnerable to shock becauseof their limited capacity to make informed decision onsecured coping strategies which is further aggravated by somehouseholds’ specific socio-economic characteristics. Attemptswere made to identify shocks being faced by households’ headsand coping strategies. Multistage sampling technique was usedto select 80 respondents and well structured questionnaire wasused to collect data through in-depth interview. Data wereanalysed using descriptive statistics to describe households’ socio-economic variables; Probit analysis was also used to determinethe relationship between personal socio-economic characteristicsof the respondents, shocks and choice of coping actions. Theresults revealed that a large share of households experiencemultidimensional shocks, which are mainly associated toecological but also suffer from other economic, demographicand social factors. Majority of households undertake copingactions in response to shocks; coping strategies employed butnot limited to include borrowing, distress sales of assets,remittances, adjustment in food intake, drawing on savings. Educational status, household size, per capita income, shocks type,coping strategies, among others are found to significantly affectthe choice of coping actions and are likely to have implicationsfor households’ future welfare status.

  7. Utilising Enterprise Risk Management Strategies to Develop a Governance and Operations Framework for a New Research Complex: A Case Study

    Science.gov (United States)

    Clyde-Smith, Jodi

    2014-01-01

    Enterprise risk management strategies were used to develop a regulatory and operational framework for a new multi-partner Research Institute that will house up to 900 staff from four different institutions in Queensland, Australia. The Institute will operate in a business environment while functioning as a research resource for the higher…

  8. A Guide for College Presidents and Governing Boards: Strategies for Eliminating Alcohol and Other Drug Abuse on Campuses.

    Science.gov (United States)

    Upcraft, M. Lee; Welty, John D.

    This guide outlines the extent of drug use and alcohol problems on college campuses and recommends five strategies for institutions of higher education: (1) develop clear policies concerning alcohol and other drugs; (2) enforce alcohol and other drug regulations; (3) provide alcohol and other drug education and prevention programs; (4) ensure…

  9. Ion channel regulation by phosphoinositides analyzed with VSPs-PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility.

    Science.gov (United States)

    Rjasanow, Alexandra; Leitner, Michael G; Thallmair, Veronika; Halaszovich, Christian R; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K(+) channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs.

  10. Ion channel regulation by phosphoinositides analyzed with VSPs – PI(4,5P2 affinity, phosphoinositide selectivity, and PI(4,5P2 pool accessibility

    Directory of Open Access Journals (Sweden)

    Alexandra eRjasanow

    2015-06-01

    Full Text Available The activity of many proteins depends on the phosphoinositide (PI content of the membrane. E.g., dynamic changes of the concentration of PI(4,5P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids.Voltage-sensitive phosphatases (VSPs turn over PI(4,5P2 to PI(4P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5P2. Because cellular PI(4,5P2 is resynthesized rapidly, steady state PI(4,5P2 changes with the degree of VSP activation and thus depends on membrane potential.Here we show that titration of endogenous PI(4,5P2 with Ci-VSP allows for the quantification of relative PI(4,5P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5P2 and PI(4P was insensitive to VSP.Surprisingly, despite comparable PI(4,5P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5P2 that differ in their accessibility to PLC and VSPs.

  11. Mitochondria-related miR-151a-5p reduces cellular ATP production by targeting CYTB in asthenozoospermia.

    Science.gov (United States)

    Zhou, Ran; Wang, Rong; Qin, Yufeng; Ji, Juan; Xu, Miaofei; Wu, Wei; Chen, Minjian; Wu, Di; Song, Ling; Shen, Hongbing; Sha, Jiahao; Miao, Dengshun; Hu, Zhibin; Xia, Yankai; Lu, Chuncheng; Wang, Xinru

    2015-12-02

    Mitochondria, acting as the energy metabolism factory, participate in many key biological processes, including the maintenance of sperm viability. Mitochondria-related microRNA (miRNA), encoded by nuclear genome or mitochondrial genome, may play an important regulatory role in the control of mitochondrial function. To investigate the potential role of mitochondria-related miRNAs in asthenozoospermia, we adopted a strategy consisting of initial screening by TaqMan Low Density Array (TLDA) and further validation with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Validation of the profiling results was conducted in two independent phases. Eventually, two seminal plasma miRNAs (sp-miRs) (miR-101-3p, let-7b-5p) were found to be significantly decreased, while sp-miR-151a-5p was significantly increased in severe asthenozoospermia cases compared with healthy controls. To further study their potential roles in asthenozoospermia, we then evaluated mitochondrial function of GC-2 cells transfected with these potentially functional miRNAs. Our results demonstrated that transfection with miR-151a-5p mimics decreased the mitochondrial respiratory activity. Besides, Adenosine Triphosphate (ATP) level was decreased when transfected with miR-151a-5p mimics. In addition, Cytochrome b (Cytb) mRNA and protein levels were also decreased when miR-151a-5p was overexpressed. These results indicate that miR-151a-5p may participate in the regulation of cellular respiration and ATP production through targeting Cytb.

  12. Brazilian policy responses to violence against women: government strategy and the help-seeking behaviors of women who experience violence.

    Science.gov (United States)

    Kiss, Ligia; d'Oliveira, Ana Flavia Lucas; Zimmerman, Cathy; Heise, Lori; Schraiber, Lilia Blima; Watts, Charlotte

    2012-06-15

    Over the past three decades, international covenants have been signed and countries have implemented strategies and legislation to address violence against women. Concurrently, strong evidence on the magnitude and impact of violence against women has emerged from around the world. Despite a growing understanding of factors that may influence women's vulnerability to violence and its effects, key questions about intervention options persist. Using evidence from a WHO household survey on domestic violence, our paper discusses women's help-seeking patterns and considers these findings in relation to Brazil's policies and strategies on violence against women. For the WHO survey, data from a large urban center (the city of São Paulo) and from a rural region (Zona da Mata Pernambucana [ZMP]) was collected. Findings from this survey indicate that in São Paulo, only 33.8% of women who experienced intimate partner violence (IPV) sought help from a formal service provider, including health, legal, social, or women's support services; in the Forest Zone of the State of Pernambuco, an even smaller proportion (17.1%) sought formal assistance. The majority of women were likely to contact only informal sources of support, such as family, friends, and neighbors. Women who used formal services were primarily those who experienced more severe levels of violence, were severely injured, had children who witnessed the violence, or whose work was disrupted by the violence. Although Brazil adopted progressive laws and national and local strategies to address violence against women (VAW), messages about violence and equality need to reach informal networks and the wider community in order to national anti-violence policies to be successful in supporting women before violence becomes intolerable.. To translate international standards and national policies into actions that genuinely reach women experiencing violence, states must carefully consider evidence on women's options and decision

  13. PRACTICE OF GOOD GOVERNANCE AND CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Bălăceanu Cristina

    2010-12-01

    Full Text Available Corporate governance reforms are occurring in countries around the globe and potentially impacting the population of the entire planet. In developing countries, such reforms occur in a larger context that is primarily defined by previous attempts at promoting “development” and recent processes of economic globalization. In this context, corporate governance reforms (in combination with the liberalising reforms associated with economic globalization, in effect represent a new development strategy for third world countries. The most basic questions that arise with respect to this situation are what the prospects for this new development model are and whether alternatives should be considered. Keywords: governance, corporate governance, economic globalization, development.

  14. MicroRNAs 99b-5p/100-5p regulated by endoplasmic reticulum stress are involved in Abeta-induced pathologies

    Directory of Open Access Journals (Sweden)

    Xiaoyang eYe

    2015-11-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia. Amyloid beta (Abeta deposition and intracellular tangles are the pathological hallmarks of AD. MicroRNAs (miRNAs are small non-coding RNAs which have been found to play very important roles and have the potential to serve as diagnostic markers during neuronal pathogenesis. In this study, we aimed to determine the roles of miR-99b-5p and miR-100-5p in Abeta-induced neuronal pathologies. We detected the expression levels of miR-99b-5p and miR-100-5p in the brains of APPswe/PS1ΔE9 double transgenic mice (APP/PS1 mice at different age stages and found both miRNAs were decreased at early stages while increased at late stages of APP/PS1 mice when compared with the age-matched wild type (WT mice. Similar phenomenon was also observed in Abeta-treated cultured cells. We also confirmed that mTOR (mammalian target of rapamycin is one of the targets of miR-99b-5p/100-5p, which is consistent with previous studies in cancer. MiR-99b-5p/100-5p have been found to promote cell apoptosis with the Abeta treatment. This effect may be induced via the mTOR pathway. In our study, we find both miR-99b-5p and miR-100-5p affect neuron survival by targeting mTOR. We also speculate that dynamic change of miR-99b-5p/100-5p levels during Abeta-associated pathologies might be attributed to Abeta-induced endoplasmic reticulum stress (ER stress, suggesting the potential role of the ER stress –miRNAs – mTOR axis in Abeta-related AD pathogenesis.

  15. Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein (VCP).

    Science.gov (United States)

    Long, Xin Hua; Zhou, Yun Fei; Peng, Ai Fen; Zhang, Zhi Hong; Chen, Xuan Yin; Chen, Wen Zhao; Liu, Jia Ming; Huang, Shan Hu; Liu, Zhi Li

    2015-05-01

    Previous studies demonstrated that increased Homo sapiens valosin-containing protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the underlying mechanism of VCP over-expression in OS remains unknown. In the present study, we found a significantly negative correlation between miR-129-5p and VCP protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = -0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p. In addition, three CPG islands in the region of miR-129-5p promoter were detected by bioinformatical prediction, and significantly higher expression of miR-129-5p and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2'-deoxycytidine (a potent DNA demethylating agent) than in those untreated cells were observed. Furthermore, lower migratory and invasive ability was found in cells with elevated miR-129-5p than in those with decreased miR-129-5p. These findings indicated that increased miR-129-5p may be mediated by demethylation and inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS management, although further studies will be necessary.

  16. Dynamics of receptor-operated Ca(2+) currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway.

    Science.gov (United States)

    Mori, Masayuki X; Itsuki, Kyohei; Hase, Hideharu; Sawamura, Seishiro; Kurokawa, Tatsuki; Mori, Yasuo; Inoue, Ryuji

    2015-01-01

    Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable, nonselective cation channels that carry receptor-operated Ca(2+) currents (ROCs) triggered by receptor-induced, phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Within the vasculature, TRPC channel ROCs contribute to smooth muscle cell depolarization, vasoconstriction, and vascular remodeling. However, TRPC channel ROCs exhibit a variable response to receptor-stimulation, and the regulatory mechanisms governing TRPC channel activity remain obscure. The variability of ROCs may be explained by their complex regulation by PI(4,5)P2 and its metabolites, which differentially affect TRPC channel activity. To resolve the complex regulation of ROCs, the use of voltage-sensing phosphoinositide phosphatases and model simulation have helped to reveal the time-dependent contribution of PI(4,5)P2 and the possible role of PI(4,5)P2 in the regulation of ROCs. These approaches may provide unprecedented insight into the dynamics of PI(4,5)P2 regulation of TRPC channels and the fundamental mechanisms underlying transmembrane ion flow. Within that context, we summarize the regulation of TRPC channels and their coupling to receptor-mediated signaling, as well as the application of voltage-sensing phosphoinositide phosphatases to this research. We also discuss the controversial bidirectional effects of PI(4,5)P2 using a model simulation that could explain the complicated effects of PI(4,5)P2 on different ROCs.

  17. Strengthening Voices: How patoralist communities and local government are shaping strategies for adaptive environmental management and poverty reduction in Tanzania's drylands

    Energy Technology Data Exchange (ETDEWEB)

    Jode, Helen de; Hesse, Ced

    2011-06-15

    Across Tanzania, climate change is being felt in the changing patterns and intensity of rainfall, and in the growing unpredictability of the seasons. The drylands are being increasingly affected, and there is an urgent need to strengthen institutional capacity and good governance for drylands planning. Pastoralism provides over 90% of the meat and milk products consumed nationally in Tanzania. The pastoralist production system successfully exploits and adapts to the disequilibrium in the dryland ecosystems, but pastoralist voices are frequently excluded from the decision-making and management of dryland resources. The marginalisation of pastoralists is resulting in falling production levels. Since 2007, IIED, the Kimmage Development Studies Centre and the Tanzania Natural Resource Forum have been undertaking a project with their partners with the specific goal of generating more informed and equitable discussion and debate on pastoralism. Using local government reform processes, the 'Strengthening Voices' project works at the community, local government and national levels - addressing the lack of knowledge and power imbalances within all three. The central pillar of the project is a training course on the economic and ecological processes at the heart of pastoral systems — clarifying the rationale that underpins livelihood strategies. National politicians, local district officials and community participants have all benefited from the training. At the end of its 1st three-year phase good progress has been made in designing and implementing tools and approaches that promote citizen access to decision-making. With their new evidence, training and advocacy skills, people are now better able to inform policy of the economic and environmental benefits of dryland livelihood systems. This booklet and accompanying DVD explain the background to the project, its achievements, and how it plans to build on its successes to roll out the project to other districts in Tanzania

  18. Global health governance and the commercial sector: a documentary analysis of tobacco company strategies to influence the WHO framework convention on tobacco control.

    Directory of Open Access Journals (Sweden)

    Heide Weishaar

    governance. Awareness of these strategies can help guard against industry efforts to disrupt the implementation of the FCTC and support the development of future, comparable initiatives in global health.

  19. Strategy of Government-Oriented Tourism Development%我国政府主导型旅游业发展策略探析

    Institute of Scientific and Technical Information of China (English)

    王珏

    2015-01-01

    At present, the rapid growth of China′s tourism industry continues to rise in the status of social development and national economy. But problems arise in the financial support, infrastructure, eco-tourism, intelligent tourism, resources sharing, environmental protection, coordination among travel security and other departments, industrial upgrading and industrial management. Thus, it is particularly important to give full play to the leading role of the government. The government should take the leading role and the dominant strategy in the tourism industry, which can sort and handle coordinating relations between the government and the tourism market, avoid blind investment and major mistakes, feasibly protect national tourism resources from destruction, and effectively guarantee the healthy and sustainable development of the tourism industry.%目前,我国旅游产业规模快速壮大,在社会发展和国民经济中的地位持续提升.但在发展的同时,也带来金融支持、基础建设、生态旅游、智能旅游、资源共享、环境保护、旅行安全等部门协调、产业升级及行业管理问题. 由此,充分发挥政府的主导作用尤为重要. 政府在旅游产业中的主导行为和采取的主导策略,能够梳理与处理协调好政府与旅游市场的关系,避免投资的盲目性与重大失误,切实保护国家旅游资源不被破坏,有效保证旅游产业健康有序的持续发展.

  20. 政府投资项目跟踪审计策略探讨%Discussion on Follow-up Auditing Strategies for Government Invested Project

    Institute of Scientific and Technical Information of China (English)

    季陆

    2014-01-01

    To carry out follow-up auditing in government invested projects is helpful for legal and reasonable use of funds, and timely controlling of construction cost. It can also improve the investment benefit, promote the project management, and reduce the loss and waste. This paper first analyzes the necessity of strengthening the follow-up auditing of government invested project, and then carries on thorough discussion on the strategies for the follow-up auditing, which is of certain referential value.%院在政府投资项目中实施跟踪审计,有利于合法、合理使用资金,对建设成本进行及时控制,也能够提高投资效益,促进项目管理,减少损失浪费。本文首先分析了加强政府投资项目跟踪审计的必要性,其次,就政府投资项目跟踪审计策略进行了较为深入的探讨,具有一定的参考价值。

  1. Diversification and Corporate Governance

    NARCIS (Netherlands)

    G.W.J. Hendrikse (George); A.A.C.J. van Oijen

    2002-01-01

    textabstractThis article addresses the impact of governance structure on diversification behavior. Hypotheses are developed regarding the differences in diversification strategy of cooperatives and stock listed companies. The analysis shows that stock listed companies are more diversified than coope

  2. A 360-degree Data Governance Strategy for Medical Institutions%面向医疗机构的360°数据管控策略研究

    Institute of Scientific and Technical Information of China (English)

    王斌; 李忠

    2012-01-01

    Objective To provide a 360-degree data governance strategy for medical institutions in order to further improve the medical information quality and access efficiency. Methods With the enterprise medical data warehouse as the basis platform, the accountability recognition mechanism of medical institutions internal data was perfected, and the active data governance was exerted with a 360-degree all-round view under data stewardship in the following areas: data quality, data integration, data security and privacy, metadata management, and master data management. Results Through this kind of full -spectrum data governance, medical institutions could greatly improve their information access efficiency and data quality, and finally step into a new elaborately-managed operational mode. Conclnsion In virtue of clear data monitoring, standardized workflow, and definitive data stewardship, this 360-degree data governance can help effectively and efficiently solve the data integration and data quality problems massively confronting medical institutions. [Chinese Medical Equipment Journal,2012,33(6) :45-48]%目的:为了进一步提高医疗数据质量和信息获取效率,提出一种面向医疗机构的360°全方位数据管控机制.方法:以企业级数据仓库为基础平台,完善医疗机构内部数据认责机制,并通过对数据质量、数据集成、数据安全与隐私、元数据管理、数据标准等细分层面的主动管控,以360°全方位视角完成整个医疗机构的数据管控.结果:通过这种全方位数据管控,医疗机构可以有效提升数据准确率和利用率,通过有效反馈,不断完善,最终步入精细化运营阶段.结论:360°全方位医疗数据管控平台通过监控数据流向、规范工作流程、明确数据职责,可以有效地解决异构系统集成问题,大幅度提升数据质量和数据访问效率.

  3. Strategies and Implementations of Government Information Charging%政府信息收费策略及其实施效果比较

    Institute of Scientific and Technical Information of China (English)

    夏义堃

    2012-01-01

    Based on theoretical analysis of government information charging, this paper points out the necessity of charging, and cards charging strategies of different countries from the points of information open and value added information access. It also has a comparative study of charging effeetiveness between marginal cost and recovery cost on information sharing, administrative cost reducing and information market competitive level, and summarizes possible problems under different eharging strategies.%通过对政府信息收费依据的分析,指出收费的必要性,并从信息公开收费与增值信息收费等角度对各国政府信息收费制度进行梳理;同时,对边际成本收费、成本性收费在促进政府信息共享、降低行政成本以及推进信息市场竞争水平等方面的实际效果进行比较,指出不同收费策略可能存在的问题。

  4. The Knowledge Governance Approach

    DEFF Research Database (Denmark)

    Foss, Nicolai

    2005-01-01

    An attempt is made to characterize a `knowledge governance approach' as a distinctive, emerging field that cuts across the fields of knowledge management, organisation studies, strategy and human resource management. Knowledge governance is taken up with how the deployment of administrative...... apparatus influences knowledge processes, such as sharing, retaining and creating knowledge. It insists on clear behavioural foundations, adopts an economizing perspective and examines efficient alignment between knowledge transactions with diverse characteristics and governance structures and mechanisms...

  5. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2012-01-01

    Most people agree that our world face daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel dominant...... perspectives in challenge per-ception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping of engineering education...... and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter strives to elicit the bodies...

  6. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2011-01-01

    Abstract: Most people agree that our world faces daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel...... dominant perspectives in challenge perception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping...... of engineering education and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter...

  7. A familial Cri-du-Chat/5p deletion syndrome resulted from rare maternal complex chromosomal rearrangements (CCRs) and/or possible chromosome 5p chromothripsis.

    Science.gov (United States)

    Gu, Heng; Jiang, Jian-hui; Li, Jian-ying; Zhang, Ya-nan; Dong, Xing-sheng; Huang, Yang-yu; Son, Xin-ming; Lu, Xinyan; Chen, Zheng

    2013-01-01

    Cri-du-Chat syndrome (MIM 123450) is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs), diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5)(p13.3p15.33) spanning ≈ 26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5) (q23;p14.1p15.31),ins(21;5)(q21;p13.3p14.1),ins(21;5)(q21;p15.31p15.33),inv(7)(p22q32)dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5) identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5). Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

  8. A familial Cri-du-Chat/5p deletion syndrome resulted from rare maternal complex chromosomal rearrangements (CCRs and/or possible chromosome 5p chromothripsis.

    Directory of Open Access Journals (Sweden)

    Heng Gu

    Full Text Available Cri-du-Chat syndrome (MIM 123450 is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs, diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5(p13.3p15.33 spanning ≈ 26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5 (q23;p14.1p15.31,ins(21;5(q21;p13.3p14.1,ins(21;5(q21;p15.31p15.33,inv(7(p22q32dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5 identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5. Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

  9. Cystein-specific ubiquitination protects the peroxisomal import receptor Pex5p against proteasomal degradation.

    Science.gov (United States)

    Schwartzkopff, Benjamin; Platta, Harald W; Girzalsky, Wolfgang; Erdmann, Ralf

    2015-05-14

    Peroxisomal matrix protein import is mediated by dynamic import receptors, which cycle between the peroxisomal membrane and the cytosol. Proteins with a type 1 peroxisomal targeting signal (PTS1) are bound by the import receptor Pex5p in the cytosol and guided to the peroxisomal membrane. After cargo translocation into the peroxisomal matrix, the receptor is released from the membrane back to the cytosol in an ATP-dependent manner by the AAA-type ATPases Pex1p and Pex6p. These mechanoenzymes recognize ubiquitinated Pex5p-species as substrates for membrane extraction. The PTS1-receptor is either polyubiquitinated via peptide-bonds at two certain lysines and results in proteasomal degradation, or monoubiquitinated via a thioester-bond at a conserved cysteine, which enables the recycling of Pex5p and further rounds of matrix protein import. To investigate the physiological relevance of the conserved N-terminal cysteine of Pex5p, the known target amino acids for ubiquitination were substituted by site-directed mutagenesis. In contrast to Pex5pC6A, Pex5pC6K turned out to be functional in PTS1 import and utilization of oleic acid, independent of the lysines at position 18 and 24. In contrast to wild-type Pex5p, Pex5pC6K displays an ubiquitination pattern, similar to the polyubiquitination pattern of Pex4p or Pex22p mutant strains. Moreover, Pex5pC6K displays a significantly reduced steady-state level when the deubiquitination enzyme Ubp15p is missing. Thus, our results indicate that not the cysteine residue but the position of ubiquitination is important for Pex5p function. The presence of the cysteine prevents polyubiquitination and rapid degradation of Pex5p.

  10. Regional governance and regional strategy development. Means of control for the energy policy turnaround using the British system of regional planning in the sub region Greater Manchester, UK; Regionale Governance und regionale Strategieentwicklung. Steuerungsmoeglichkeiten fuer die Energiewende am Beispiel des englischen Regionalplanungssystems in der Sub-Region Greater Manchester, UK

    Energy Technology Data Exchange (ETDEWEB)

    Faller, Fabian

    2011-07-01

    The contribution under consideration reports on control structures in the energy sector at regional level using the region of Greater Manchester in Northwest England as an example. The change to renewable energies is the main focus of this contribution. The strategy development process is a subject of the analytic part of this contribution. The main questions of this contribution are: (1) What are the characteristics of the Regional Governance in Greater Manchester in terms of energy supply?; (2) How does the regional governance in Greater Manchester work?; (3) How can the regional governance in the Greater Manchester be assessed with regard to the energy supply?.

  11. Inhibitory effects of gallic acid ester derivatives on Saccharomyces cerevisiae multidrug resistance protein Pdr5p.

    Science.gov (United States)

    Pereira Rangel, Luciana; Fritzen, Márcio; Yunes, Rosendo Augusto; Leal, Paulo César; Creczynski-Pasa, Tânia Beatriz; Ferreira-Pereira, Antônio

    2010-05-01

    Overexpression of the Saccharomyces cerevisiae ABC transporter Pdr5p confers resistance to a range of structurally unrelated xenobiotics. This property allows Pdr5p to be used as a target for novel multidrug resistance reversal reagents or chemosensitizers. Herein, we report the effects of gallic acid derivatives with substitutions either on the ester moiety or in the benzene ring on the activity of Pdr5p. Compounds with a longer side chain (8-16 carbons) resulted in greater inhibition of Pdr5p ATPase. Derivatives with side chains of 8-12 carbons that retained hydroxyl groups on the benzene ring extensively inhibited Pdr5p ATPase activity. These compounds almost completely inhibited the efflux of the Pdr5p fluorescent substrate Rhodamine 6G and at 25 muM chemosensitized the Pdr5p-overexpressing strain AD124567 to fluconazole (0.4 mg mL(-1)). Gallic acid derivatives may be a new class of Pdr5p inhibitors.

  12. MULTIPLET FINE-STRUCTURE IN THE PHOTOEMISSION OF THE GADOLINIUM AND TERBIUM 5P LEVELS

    NARCIS (Netherlands)

    THOLE, BT; WANG, XD; HARMON, BN; LI, DQ; DOWBEN, PA

    1993-01-01

    Fine structure is observed in the photoemission of the gadolinium and terbium 5p levels. The 5p levels are split into multiplets due to spin-orbit splitting and to Coulomb and exchange interactions with the f shell. The calculated theoretical spectra are in good agreement with the experimental resul

  13. Governance Strategies and Welfare Effects

    DEFF Research Database (Denmark)

    Trifkovic, Neda

    Using an original dataset from the Vietnamese catfish sector, we study the impact of vertical coordination options on household welfare and the implications of different stages of vertical coordination for the success of the whole sector. The welfare gain from contract farming and employment...

  14. Governance Strategies and Welfare Effects

    DEFF Research Database (Denmark)

    Trifkovic, Neda

    Using an original dataset from the Vietnamese catfish sector, we study the impact of vertical coordination options on household welfare and the implications of different stages of vertical coordination for the success of the whole sector. The welfare gain from contract farming and employment...... on processor-owned estate farms is estimated using a maximum simulated likelihood estimator. Our results show positive welfare effects from participating in contract farming, but not from employment on processor-owned estate farms. The results imply that contract farming presents opportunities for economic...

  15. Interactive governance

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob; Peters, B. Guy

    Governance has become one of the most commonly used concepts in contemporary political science. It is, however, often used to mean a variety of different things. This book helps to clarify this conceptual muddle by concentrating on one variety of governance-interactive governance. The authors argue...... that although the state may remain important for many aspects of governing, interactions between state and society represent an important, and perhaps increasingly important, dimension of governance. These interactions may be with social actors such as networks, with market actors or with other governments......, but all these forms represent means of governing involving mixtures of state action with the actions of other entities.This book explores thoroughly this meaning of governance, and links it to broader questions of governance. In the process of explicating this dimension of governance the authors also...

  16. Government Statistics Strategy Research Based on Big Data Usability%基于大数据可用性的政府统计策略研究

    Institute of Scientific and Technical Information of China (English)

    孙立; 杨军; 潘坤友

    2014-01-01

    随着大数据的指数型增长,不确定数据大幅度增加,大数据应用深度和广度有限,对传统的政府统计平台建设和统计思路带来严峻的挑战。在分析大数据可用性理论的基础上,提出大数据统计平台建设要求,并给出实施路径与建设策略。%With the exponential growth of big data,uncertain data significantly increase,but the depth and the breadth of big data applications is limited,which brings serious challenges to building traditional government statistics platform and statistics methods. On the basis of analyzing big data usability,the paper puts forward big data statistics platform construc-tion requirements,and further proposes the implementation path and the building strategy.

  17. The Role of Government and Markets in the Strategy “Europe 2020” of the European Union: A Robust Political Economy Analysis

    Directory of Open Access Journals (Sweden)

    Wandel Jürgen

    2016-03-01

    Full Text Available The EU’s current ten year strategy “Europe 2020” aims to set out a vision of a European social market economy for the 21st century that will promote economic growth with social and ecological attributes. This article analyzes the roles ascribed to the government and the market and the extent this role allocation is suitable to enhance growth of the European Union’s member states. Based on a robust political economy framework it is argued that this new economic policy concept is in essence a technocratic approach and a form of selective interventionism. As such it suffers from three major shortcomings: (1 it underestimates the difficulties of gathering and analyzing the relevant information necessary for steering the economy in the desired direction, (2 it encourages rent-seeking rather than productive entrepreneurship, and (3 it may cause a subtle transformation of the societal order through the diminution of individual liberties. It is contended that while an interventionist policy approach meets the preferences of large parts of the population, not the least in Germany, it is unlikely to boost economic growth and employment in the EU.

  18. Consultancy support to GCC ICT Authorities to assist in creating common guidelines and strategies to enhance the development of eGovernment within the eGULF Initiative: final report

    NARCIS (Netherlands)

    Millard, J.; Shahin, J.

    2010-01-01

    This consultancy support analyses global experience in eGovernment cooperation between responsible authorities, examines the needs and existing strategies of each of the six GCC Countries, identifies common elements and areas where mutual cooperation will be beneficial, and proposes common guideline

  19. 政府行为对物流企业战略影响的实证分析%An Analysis of the Influence of Government Action on Logistic Business Strategy

    Institute of Scientific and Technical Information of China (English)

    陈青兰; 赵梦楚

    2012-01-01

    This paper is about the influence of Government action on the logistic business strategy. Combining the government behavior theory and enterprise strategic theory, This paper put forward three hypotheses through logical deduction of the influence on business strategy by government action. It goes on with a structural analysis of 30 logistic enterprises using a content analysis, and the quantitative data acquired show the effect of 10 government action index on corporate strategy. The paper brings forward that logistic is inevitably influenced by government action, and that government action has greater positive than impact, and more direct than indirect impact on logistic business strategy. In making strategic decision, business should find out impacts of government action on corporate strategy and adjust their business accordingly in order to maximize the benefit of resources from the Government. business negative logistics strategy%通过逻辑演绎,给出企业战略受政府行为彰响的3个假设,在此基础上,应用内容分析法对30家物流企业的资料进行结构化分析,得到定量数据,从而验证了10种政府行为指标对企业战略的影响效应。研究认为:政府行为对物流企业的影响具有必然性;政府行为对物流企业战略的积极影响多于消极影响,直接影响多于间接影响。指出物流企业在战略管理过程中应该分析政府行为对企业战略的不同影响。适时调整企业战略,最大限度地利用政府提供的资源。

  20. Enterprise IT governance key decision-making based on strategy alignment and analytic hierarchy process%基于战略匹配和层次分析的企业IT治理关键问题决策

    Institute of Scientific and Technical Information of China (English)

    计春阳; 唐志豪

    2012-01-01

    The alignment between business strategy and IT strategy is the bases for good IT governance performance. And enterprises have to do five key decisions for their IT governance. To convert the alignment ideal into quantitative model so as to support enterprise IT governance decision, the Analytic Network Process (ANP) algorithm was introduced , and collaboration between business and IT strategy was simulated. Business strategy management of Porter, and strategy alignment management of Henderson were borrowed to represent business strategy and IT strategy. An IT governance key decision-making model based on the quantitative results of strategic alignment was put forward and validated through computation and analysis of real cases.%企业战略与IT战略之间的匹配是确保IT治理取得良好绩效的重要前提.企业的IT治理必须完成五个关键问题的决策.为有效地将战略对应的思想转化为量化模型,支持企业决策,本文引入网络层次分析法模拟企业战略与IT战略之间的匹配关系,分别借用Porter的战略管理理论和Henderson的战略匹配模型代表企业战略和IT战略,提出了基于战略匹配的企业IT治理五个关键问题决策模型,并通过实例分析与运算验证了该模型的有效性.

  1. Interactive Governance

    DEFF Research Database (Denmark)

    Bang, Henrik

    2016-01-01

    Governance analysis has exploded in recent years, and it has become nearly impossible to tell what difference the concept and practice of governance makes from those of government and state. In addition governance analysis has been placed more and more in the shadow of the new institutionalisms and...... and growth. However, interactive governance is not a property or effect of institutions; nor does it apply solely to those individuals who seek success above everything else. It is connective more than individualistic or collectivistic in nature; and it manifests a governability capacity which...

  2. 浅析突发事件处理中政府与媒体的沟通策略%on Government and Media's Communication Strategies During the Process of Emergencies

    Institute of Scientific and Technical Information of China (English)

    李姗姗

    2012-01-01

    在突发事件的处理过程中,政府部门能否成功与媒体沟通、把握舆论导向已经成为决定突发事件处理效果的关键因素。因此在突发事件的处理中,政府应该要掌握与媒体沟通的各种策略。主要体现为政府与媒体沟通中的信息掌控策略——主动提供;政府与媒体沟通中的信息处理策略——真实有效;政府与媒体沟通中的信息发布策略——及时渐进;政府与媒体沟通中的信息提供策略——口径一致;政府与媒体沟通中的信息表达策略——有人情味;政府与媒体沟通中的信息选择策略——勇于担当。%During the process of emergencies, it has become a key factor to decide the effect of handling the emergencies, whether the government can communicate with media successfully and steer the public opinions. So, in the course of handling the emergencies, government should master all kinds of communication strategies with media. Mainly , they are strategies of controlling the information in government and media communication, to provide actively; They are they are strategies of han- dling the information in government and media communication,to he real effective;They are they are strategies of puhlishng the information in government and media communication, to be timely and gradual;They are they are strategies of providng the in- formation in government and media communication, to be one voice; They are they are strategies of expressling the information in government and media communication,to be human;

  3. LPS-induced clustering of CD14 triggers generation of PI(4,5)P2.

    Science.gov (United States)

    Płóciennikowska, Agnieszka; Zdioruk, Mykola I; Traczyk, Gabriela; Świątkowska, Anna; Kwiatkowska, Katarzyna

    2015-11-15

    Bacterial lipopolysaccharide (LPS) induces strong pro-inflammatory reactions after sequential binding to CD14 protein and TLR4 receptor. Here, we show that CD14 controls generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in response to LPS binding. In J774 cells and HEK293 cells expressing CD14 exposed to 10-100 ng/ml LPS, the level of PI(4,5)P2 rose in a biphasic manner with peaks at 5-10 min and 60 min. After 5-10 min of LPS stimulation, CD14 underwent prominent clustering in the plasma membrane, accompanied by accumulation of PI(4,5)P2 and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms Iα and Iγ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region. Clustering of CD14 with antibodies, without LPS and TLR4 participation, was sufficient to trigger PI(4,5)P2 elevation. The newly generated PI(4,5)P2 accumulated in rafts, which also accommodated CD14 and a large portion of PIP5K Iα and PIP5K Iγ. Silencing of PIP5K Iα and PIP5K Iγ, or application of drugs interfering with PI(4,5)P2 synthesis and availability, abolished the LPS-induced PI(4,5)P2 elevation and inhibited downstream pro-inflammatory reactions. Taken together, these data indicate that LPS induces clustering of CD14, which triggers PI(4,5)P2 generation in rafts that is required for maximal pro-inflammatory signaling of TLR4.

  4. Dynamics of receptor-operated Ca2+ Currents Through TRPC Channels Controlled via the PI(4,5P2-PLC Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Masayuki X Mori

    2015-02-01

    Full Text Available Transient receptor potential canonical (TRPC channels are Ca2+-permeable, nonselective cation channels that carry receptor-operated Ca2+ currents (ROCs triggered by receptor-induced, phospholipase C (PLC-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5P2. Within the vasculature, TRPC channel ROCs contribute to smooth muscle cell depolarization, vasoconstriction and vascular remodeling. However, TRPC channel ROCs exhibit a variable response to receptor-stimulation, and the regulatory mechanisms governing TRPC channel activity remain obscure. The variability of ROCs may be explained by their complex regulation by PI(4,5P2 and its metabolites, which differentially affect TRPC channel activity. To resolve the complex regulation of ROCs, the use of voltage-sensing phosphoinositide phosphatases and model simulation have helped to reveal the time-dependent contribution of PI(4,5P2 and the possible role of PI(4,5P2 in the regulation of ROCs. These approaches may provide unprecedented insight into the dynamics of PI(4,5P2 regulation of TRPC channels and the fundamental mechanisms underlying transmembrane ion flow. Within that context, we summarize the regulation of TRPC channels and their coupling to receptor-mediated signaling, as well as the application of voltage-sensing phosphoinositide phosphatases to this research. We also discuss the controversial bidirectional effects of PI(4,5P2 using a model simulation that could explain the complicated effects of PI(4,5P2 on different ROCs.

  5. Crystal Structure of Prp5p Reveals Interdomain Interactions that Impact Spliceosome Assembly

    Directory of Open Access Journals (Sweden)

    Zhi-Min Zhang

    2013-12-01

    Full Text Available The DEAD-box adenosine triphosphatase (ATPase Prp5p facilitates U2 small nuclear ribonucleoprotein particle (snRNP binding to the intron branch site region during spliceosome assembly. We present crystal structures of S. cerevisiae Prp5p alone and in complex with ADP at 2.12 Å and 1.95 Å resolution. The three-dimensional packing of Prp5p subdomains differs strikingly from that so far observed in other DEAD-box proteins: two RecA-like subdomains adopt an “open state” conformation stabilized by extensive interactions involving sequences that flank the two subdomains. This conformation is distinct from that required for ATP hydrolysis. Consistent with this, Prp5p mutations that destabilize interdomain interactions exhibited increased ATPase activity in vitro and inhibited splicing of suboptimal branch site substrates in vivo, whereas restoration of interdomain interactions reversed these effects. We conclude that the Prp5p open state conformation is biologically relevant and that disruption of the interdomain interaction facilitates a large-scale conformational change of Prp5p during U2 snRNP-branch site recognition.

  6. CRAC channel is inhibited by neomycin in a Ptdlns(4,5)P2-independent manner.

    Science.gov (United States)

    Huang, Kun; Wang, Xuemei; Liu, Yanjun; Zhao, Yi

    2015-03-01

    Depletion of intracellular Ca(2+) stores evokes store-operated Ca(2+) entry through the Ca(2+) release-activated Ca(2+) (CRAC) channels. In this study, we found that the store-operated Ca(2+) entry was inhibited by neomycin, an aminoglycoside that strongly binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Patch clamp recordings revealed that neomycin blocked the CRAC currents reconstituted by co-expression of Orai1 and Stim1 in HEK293 cells. Using a rapamycin-inducible PtdIns(4,5)P2-specific phosphatase (Inp54p) system to manipulate the PtdIns(4,5)P2 in the plasma membrane, we found that the CRAC current was not altered by PtdIns(4,5)P2 depletion. This result suggests that PtdIns(4,5)P2 is not required for CRAC channel activity, and thereby, neomycin inhibits CRAC channels in a manner that is independent of neomycin-PtdIns(4,5)P2 binding.

  7. Emerging roles of PtdIns(4,5)P2--beyond the plasma membrane.

    Science.gov (United States)

    Tan, Xiaojun; Thapa, Narendra; Choi, Suyong; Anderson, Richard A

    2015-11-15

    Phosphoinositides are a collection of lipid messengers that regulate most subcellular processes. Amongst the seven phosphoinositide species, the roles for phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at the plasma membrane, such as in endocytosis, exocytosis, actin polymerization and focal adhesion assembly, have been extensively studied. Recent studies have argued for the existence of PtdIns(4,5)P2 at multiple intracellular compartments, including the nucleus, endosomes, lysosomes, autolysosomes, autophagic precursor membranes, ER, mitochondria and the Golgi complex. Although the generation, regulation and functions of PtdIns(4,5)P2 are less well-defined in most other intracellular compartments, accumulating evidence demonstrates crucial roles for PtdIns(4,5)P2 in endolysosomal trafficking, endosomal recycling, as well as autophagosomal pathways, which are the focus of this Commentary. We summarize and discuss how phosphatidylinositol phosphate kinases, PtdIns(4,5)P2 and PtdIns(4,5)P2-effectors regulate these intracellular protein and membrane trafficking events.

  8. Smooth muscle length-dependent PI(4,5)P2 synthesis and paxillin tyrosine phosphorylation.

    Science.gov (United States)

    Sul, D; Baron, C B; Broome, R; Coburn, R F

    2001-07-01

    We studied effects of increasing the length of porcine trachealis muscle on 5.5 microM carbachol (CCh)-evoked phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] synthesis and other parameters of phosphatidylinositol (PI) turnover. PI(4,5)P2 resynthesis rates in muscle held at 1.0 optimal length (L(o)), measured over the first 6 min of CCh stimulation, were 140 +/- 12 and 227 +/- 14% of values found in muscle held at 0.5 L(o) and in free-floating muscle, respectively. Time-dependent changes in cellular masses of PI(4,5)P2, PI, and phosphatidic acid, and PI resynthesis rates, were also altered by the muscle length at which contraction occurred. In free-floating muscle, CCh did not evoke increases in tyrosine-phosphorylated paxillin (PTyr-paxillin), an index of beta1-integrin signaling; however, there were progressive increases in PTyr-paxillin in muscle held at 0.5 and 1.0 L(o) during contraction, which correlated with increases in PI(4,5)P2 synthesis rates. These data indicate that PI(4,5)P2 synthesis rates and other parameters of CCh-stimulated inositol phospholipid turnover are muscle length-dependent and provide evidence that supports the hypothesis that length-dependent beta1-integrin signals may exert control on CCh-activated PI(4,5)P2 synthesis.

  9. Electronic Government

    DEFF Research Database (Denmark)

    Wimmer, Maria A.; Traunmüller, Roland; Grönlund, Åke

    This book constitutes the refereed proceedings of the 4th International Conference on Electronic Government, EGOV 2005, held in Copenhagen, Denmark, in August 2005. The 30 revised papers presented were carefully reviewed and selected from numerous submissions, and assess the state-of-the-art in e-government/e-governance...

  10. Identification of Blood Let-7e-5p as a Biomarker for Ischemic Stroke

    Science.gov (United States)

    Guo, Yi; Li, Lu; Zhang, Yanwei; Zhou, Li; Yang, Binyao; Wu, Shuang; Zhang, Ying; Xie, Changhui; Li, Shanshan; Cheng, Jinquan

    2016-01-01

    Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p. The results suggest that the blood level of let-7e-5p was significantly higher in patients with ischemic stroke than in controls (p<0.05). Higher levels of let-7e-5p were associated with increased occurrence of ischemic stroke (adjusted OR, 1.89; 95% CI, 1.61~2.21, p<0.001) in the combined population. The addition of let-7e-5p to traditional risk factors led to an improvement in the area under the curve, which increased from 0.74 (95% CI, 0.70~0.78) to 0.82 (95% CI, 0.78~0.85), with a net reclassification improvement of 16.76% (p<0.0001) and an integrated discrimination improvement of 0.10 (p<0.0001) for patients with ischemic stroke. Bioinformatics prediction and cell experiments suggested that the expression levels of four genes enriched in the MAPK signaling pathway were down-regulated by let-7e-5p transfection. Specifically, the expression levels of the genes CASP3 and NLK were significantly lower in ischemic stroke patients than in controls and were negatively correlated with let-7e-5p expression. In summary, our study suggests the potential use of blood let-7e-5p as a biomarker for ischemic stroke and indicates its involvement in the related pathomechanism. PMID:27776139

  11. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Menard, Claude

    2014-01-01

    Plural governance is a form of governance where a firm both makes and buys similar goods or services. Despite a widespread use of plural governance there are no transaction cost models of how plural governance affects performance. This paper reviews the literature about plural forms and proposes...... a model relating transaction cost and resource-based variables to the cost of the plural form. The model is then used to analyze when the plural form is efficient compared to alternative governance structures. We also use the model to discuss the strength of three plural form synergies....

  12. Program governance

    CERN Document Server

    Khan, Muhammad Ehsan

    2014-01-01

    FOUNDATION OF GOVERNANCEGovernanceDefining GovernanceGovernance at Multiple LevelsSummaryReferencesTransaction Cost EconomicsTransactions-Core Elements and Attributes     Behavioral Assumptions     Governance Structure AttributesHazards of Concern     Incomplete Contracting     Bilateral Dependency and Fundamental Transformation     Adaptation or MaladaptationLinking Governance, Governance Structures, and ContractsThe Impact of Asset Specificity and Behavioral Assumptions on ContractsAp

  13. Corporate governance cycles during transition

    DEFF Research Database (Denmark)

    Mygind, Niels; Demina, Natalia; Gregoric, Aleksandra

    2004-01-01

    -nancial system. To provide simple hypothesis tests, we use Russian enterprise data for 1995-2003 and Slovenian data covering 1998-2003. In spite of differences in institutional development, con-cerning privatization and development of corporate governance institutions, we find that govern-ance cycles are broadly...... of ownership on managers, external domestic and foreign owners. JEL-codes: G3, J5, P2, P3 - Keywords: corporate governance, life-cycle, privatization, ownership change, transition economies, Russia and Slovenia.......Ownership is determined by firm specific factors and the environment. Firms change over their life-cycle. The governance cycle - here defined as changes in identity of the dominant owner and own-ership concentration - is marked by key phases including start-up, growth, and possibly a restructur...

  14. PI(3,5)P2 biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms.

    Science.gov (United States)

    Mironova, Yevgeniya A; Lenk, Guy M; Lin, Jing-Ping; Lee, Seung Joon; Twiss, Jeffery L; Vaccari, Ilaria; Bolino, Alessandra; Havton, Leif A; Min, Sang H; Abrams, Charles S; Shrager, Peter; Meisler, Miriam H; Giger, Roman J

    2016-03-23

    Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4, Pikfyve or Vac14, encoding key components of the PI(3,5)P2 biosynthetic complex, each lead to impaired OL maturation, severe CNS hypomyelination and delayed propagation of compound action potentials. Primary OLs deficient in Fig4 accumulate large LAMP1(+) and Rab7(+) vesicular structures and exhibit reduced membrane sheet expansion. PI(3,5)P2 deficiency leads to accumulation of myelin-associated glycoprotein (MAG) in LAMP1(+)perinuclear vesicles that fail to migrate to the nascent myelin sheet. Live-cell imaging of OLs after genetic or pharmacological inhibition of PI(3,5)P2 synthesis revealed impaired trafficking of plasma membrane-derived MAG through the endolysosomal system in primary cells and brain tissue. Collectively, our studies identify PI(3,5)P2 as a key regulator of myelin membrane trafficking and myelinogenesis.

  15. MicroRNA-125b-5p mimic inhibits acute liver failure

    Science.gov (United States)

    Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P.; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep

    2016-01-01

    The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF. PMID:27336362

  16. 大股东干预对上市公司多元化投资影响的实证分析%The Empirical Analysis on the Impact of the Listed Companies' Diversification Strategies from Government Interference

    Institute of Scientific and Technical Information of China (English)

    梁瀛

    2012-01-01

    This article is mainly about the impact from government interference. The local government is the ultimate owner of state-owned enterprises (SOE), and is also the important participant in market-based economy. This article takes analysis on the Impact of the Listed Companies' Diversification Strategies for the big shareholder' character, from the viewpoint that the local government is a participant in the market.%本文主要从大股东干预的角度出发,通过分析政府作为国有上市公司大股东终极所有权人以及地方政府作为市场管制主体的角度来分析大股东性质对上市公司多元化投资决策的影响。

  17. PtdIns(4,5)P2 signaling regulates ATG14 and autophagy.

    Science.gov (United States)

    Tan, Xiaojun; Thapa, Narendra; Liao, Yihan; Choi, Suyong; Anderson, Richard A

    2016-09-27

    Autophagy is a regulated self-digestion pathway with fundamental roles in cell homeostasis and diseases. Autophagy is regulated by coordinated actions of a series of autophagy-related (ATG) proteins. The Barkor/ATG14(L)-VPS34 (a class III phosphatidylinositol 3-kinase) complex and its product phosphatidylinositol 3-phosphate [PtdIns(3)P] play key roles in autophagy initiation. ATG14 contains a C-terminal Barkor/ATG14(L) autophagosome-targeting sequence (BATS) domain that senses the curvature of PtdIns(3)P-containing membrane. The BATS domain also strongly binds PtdIns(4,5)P2, but the functional significance has been unclear. Here we show that ATG14 specifically interacts with type Iγ PIP kinase isoform 5 (PIPKIγi5), an enzyme that generates PtdIns(4,5)P2 in mammalian cells. Autophagosomes have associated PIPKIγi5 and PtdIns(4,5)P2 that are colocalized with late endosomes and the endoplasmic reticulum. PtdIns(4,5)P2 generation at these sites requires PIPKIγi5. Loss of PIPKIγi5 results in a loss of ATG14, UV irradiation resistance-associated gene, and Beclin 1 and a block of autophagy. PtdIns(4,5)P2 binding to the ATG14-BATS domain regulates ATG14 interaction with VPS34 and Beclin 1, and thus plays a key role in ATG14 complex assembly and autophagy initiation. This study identifies an unexpected role for PtdIns(4,5)P2 signaling in the regulation of ATG14 complex and autophagy.

  18. Role of mast cell-miR-490-5p in irritable bowel syndrome

    Science.gov (United States)

    Ren, Hai-Xia; Zhang, Fa-Can; Luo, He-Sheng; Zhang, Guo; Liang, Lie-Xin

    2017-01-01

    AIM To determine the functional role of miR-490-5p in mast cell proliferation and apoptosis, and in the mast cell tryptase/PAR-2 signal pathway. METHODS The 3rd generation of lentivirus vector systems containing enhanced green fluorescent protein (EGFP) (Ruisai Inc., Shanghai, China), which acts as a reporter gene was used to construct the mmu-miR-490-5p lentivirus expression vector pEGFP-antagomiR-490-5p, and the lentivirus vector pEGFP-negative was used as a negative control. The stably transfected mast cell line p815 was then constructed. GFP positive cells were successfully transfected cells. We determined the expression of miR-490-5p in p815 mast cells before and after transfection using quantitative real-time PCR (qRT-PCR). In addition, after transduction with the lentivirus vectors, the role of miR-490-5p in mast cell proliferation and apoptosis was investigated using the CCK-8 assay and flow cytometry, respectively. The mRNA levels of tryptase and PAR-2 were detected by qRT-PCR and the protein levels were detected by Western blot. RESULTS The inhibition of miR-490-5p expression promoted apoptosis and inhibited proliferation of p815 mast cells. The mRNA levels of tryptase and PAR-2 were significantly increased after transfection compared with the control group, tryptase (P = 0.721, normal vs null; P = 0.001, siRNA vs normal; P = 0.002, siRNA vs null) and PAR-2 (P = 0.027, siRNA vs null; P = 0.353, normal vs null; P = 0.105, siRNA vs normal). The protein levels of tryptase and PAR2 were slightly higher in the siRNA group than those in the control group, but the difference was not statistically significant (P > 0.05). CONCLUSION miR-490-5p plays a vital role in the pathogenesis of irritable bowel syndrome by affecting mast cell proliferation and apoptosis; with down-regulation of miR-490-5p, the mRNA level of mast cell tryptase and PAR-2 increased, and the protein level increased, but the difference was not statistically significant.

  19. Remaking Governance.

    Science.gov (United States)

    Carver, John

    2000-01-01

    The Policy Governance model's philosophical foundations lie in Rousseau's social contract, Greenleaf's servant-leadership, and modern management theory. Policy Governance stresses primacy of the owner-representative role; full-board authority; superintendents as chief executive officers; authoritative prescription of "ends," bounded freedom for…

  20. Diversification and Corporate Governance

    OpenAIRE

    Hendrikse, George; van Oijen, A.A.C.J.

    2002-01-01

    textabstractThis article addresses the impact of governance structure on diversification behavior. Hypotheses are developed regarding the differences in diversification strategy of cooperatives and stock listed companies. The analysis shows that stock listed companies are more diversified than cooperatives, related as well as unrelated.

  1. Competence, governance, and entrepreneurship

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahnke, Volker

    This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives on the f......, and entrepreneurship to advance and stimulate economic strategy research....

  2. Howland Island Site 5P 2/7/2001 19-20M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (0 48.340 N, 176 37.272 W), between 19 and 20 meters along a permanent transect.

  3. Baker Island Site 5P 1/24/2004 12-13M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 12 and 13 meters along a permanent transect.

  4. MicroRNA-199a-5p Affects Porcine Preadipocyte Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Xin-E Shi

    2014-05-01

    Full Text Available MicroRNAs (miRNAs, a class of small non-coding RNAs, have emerged as novel and potent regulators of adipogenesis. However, few miRNAs have been fully investigated in porcine adipogenesis, given the fact that pig is not only an apropos model of human obesity research, but also a staple meat source of human diet. In this study, we showed that miRNA-199a-5p is highly expressed in porcine subcutaneous fat deposits compared to several other tissue types and organs measured alongside. Overexpression of miR-199a-5p in porcine preadipocytes significantly promoted cell proliferation while attenuating the lipid deposition in porcine adipocytes. By target gene prediction and experimental validation, we demonstrated that caveolin-1 (Cav-1 may be a bona fide target of miR-199a-5p in porcine adipocytes, accounting for some of miR-199a-5p’s functions. Taken together, our data established a role of miR-199a-5p in porcine preadipocyte proliferation and differentiation, which is at least partially played by downregulating Cav-1.

  5. Howland Island Site 5P 2/7/2001 34-35M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (0 48.340 N, 176 37.272 W), between 34 and 35 meters along a permanent transect.

  6. Howland Island Site 5P 3/17/2000 50-51M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 50 and 51 meters along a permanent transect.

  7. Howland Island Site 5P 1/31/2002 8-9M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 8 and 9 meters along a permanent transect.

  8. Rose Atoll Site 5P 2/10/2004 14-13M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Rose Atoll, site 5P (14 33.280 S, 168 09.878 W), between 14 and 15 meters along a permanent transect.

  9. Rose Atoll Site 5P 2/10/2004 46-45M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Rose Atoll, site 5P (14 33.280 S, 168 09.878 W), between 46 and 47 meters along a permanent transect.

  10. Kingman Reef Site 5P 3/17/2002 28-29M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Kingman Reef, site 5P (6 23.805N, 162 20.941W), between 28 and 29 meters along a permanent transect.

  11. Johnston Atoll Site 5P 7/2/2000 30-31M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 5P (16 46.392N, 169 29.893W), between 30 and 31 meters along a permanent transect.

  12. Kingman Reef Site 5P 4/3/2004 26-27M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Kingman Reef, site 5P (6 23.805N, 162 20.941W), between 26 and 27 meters along a permanent transect.

  13. Kingman Reef Site 5P 3/17/2002 30-31M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Kingman Reef, site 5P (6 23.805N, 162 20.941W), between 30 and 31 meters along a permanent transect.

  14. Howland Island Site 5P 1/21/2004 17-18M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 17 and 18 meters along a permanent transect.

  15. Howland Island Site 5P 1/21/2004 36-37M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 36 and 37 meters along a permanent transect.

  16. Rose Atoll Site 5P 2/20/2002 18-19M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Rose Atoll, site 5P (14 33.280S, 168 09.878W), between 18 and 19 meters along a permanent transect.

  17. Rose Atoll Site 5P 2/10/2004 22-21M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Rose Atoll, site 5P (14 33.280 S, 168 09.878 W), between 22 and 23 meters along a permanent transect.

  18. Baker Island Site 5P 1/24/2004 49-50M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 49 and 50 meters along a permanent transect.

  19. Auditory pathology in cri-du-chat (5p-) syndrome: phenotypic evidence for auditory neuropathy.

    Science.gov (United States)

    Swanepoel, D

    2007-10-01

    5p-(cri-du-chat syndrome) is a well-defined clinical entity presenting with phenotypic and cytogenetic variability. Despite recognition that abnormalities in audition are common, limited reports on auditory functioning in affected individuals are available. The current study presents a case illustrating the auditory functioning in a 22-month-old patient diagnosed with 5p- syndrome, karyotype 46,XX,del(5)(p13). Auditory neuropathy was diagnosed based on abnormal auditory evoked potentials with neural components suggesting severe to profound hearing loss in the presence of cochlear microphonic responses and behavioral reactions to sound at mild to moderate hearing levels. The current case and a review of available reports indicate that auditory neuropathy or neural dys-synchrony may be another phenotype of the condition possibly related to abnormal expression of the protein beta-catenin mapped to 5p. Implications are for routine and diagnostic specific assessments of auditory functioning and for employment of non-verbal communication methods in early intervention.

  20. Baker Island Site 5P 3/19/2000 34-35M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 34 and 35 meters along a permanent transect.

  1. Howland Island Site 5P 3/17/2000 87-88M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 87 and 88 meters along a permanent transect.

  2. Kingman Reef Site 5P 4/1/2000 40-41M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Kingman Reef, site 5P (06 23.805N, 162 20.941W), between 40 and 41 meters along a permanent transect.

  3. Kingman Reef Site 5P 4/3/2004 23-24M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Kingman Reef, site 5P (6 23.805N, 162 20.941W), between 23 and 24 meters along a permanent transect.

  4. Baker Island Site 5P 1/29/2002 18-19M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 18 and 19 meters along a permanent transect.

  5. Baker Island Site 5P 1/24/2004 33-34M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 33 and 34 meters along a permanent transect.

  6. Howland Island Site 5P 1/21/2004 39-40M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 39 and 40 meters along a permanent transect.

  7. Baker Island Site 5P 3/19/2000 29-30M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 29 and 30 meters along a permanent transect.

  8. Howland Island Site 5P 2/7/2001 23-24M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (0 48.340 N, 176 37.272 W), between 23 and 24 meters along a permanent transect.

  9. Howland Island Site 5P 3/17/2000 85-86M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 85 and 86 meters along a permanent transect.

  10. Rose Atoll Site 5P 2/10/2004 29-28M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Rose Atoll, site 5P (14 33.280 S, 168 09.878 W), between 29 and 30 meters along a permanent transect.

  11. Howland Island Site 5P 1/21/2004 30-31M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 30 and 31 meters along a permanent transect.

  12. Baker Island Site 5P 2/9/2001 80-81M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (0 11.781N, 176 29.176W), between 80 and 81 meters along a permanent transect.

  13. Rfc5p regulates alternate RFC complex functions in sister chromatid pairing reactions in budding yeast.

    Science.gov (United States)

    Maradeo, Marie E; Garg, Anisha; Skibbens, Robert V

    2010-11-01

    Sister chromatid pairing reactions, termed cohesion establishment, occur during S-phase and appear to be regulated by Replication Factor C (RFC) complexes. For instance, RFCs that contain Ctf18p exhibit pro-establishment activities while those that contain Elg1p exhibit anti-establishment activities. It remains unknown whether Ctf18p-RFC and Elg1p-RFC functions are simply opposing or instead reveal complicated and non-parallel regulatory mechanisms. To better understand the nature of these novel pathways, we analyzed the small RFC subunit Rfc5p that is common to both Ctf18p-RFC and Elg1p-RFC. Despite this commonality, the data show that diminished Rfc5p function rescues ctf7/eco1 mutant cell phenotypes, revealing that Rfc5p promotes anti-establishment activities. This rescue is specific to establishment pathways in that rfc5-1 greatly accentuates growth defects when expressed in scc2 (deposition), mcd1/scc1 or smc3 (cohesion maintenance) mutated cells. Our results reveal for the first time a role for small RFC subunits in directing RFC complex functions-in this case towards anti-establishment pathways. We further report that Pds5p exhibits both establishment and anti-establishment functions in cohesion. This duality suggests that categorizations of establishment and anti-establishment activities require further examination.

  14. Closure of the telephone switchboard at 5 p.m. on 20 December

    CERN Multimedia

    Communications Support Section

    2013-01-01

    Exceptionally, the telephone switchboard will close at 5 p.m. on Friday 20 December, instead of 6 p.m. (usual time), to allow time for all systems to be properly closed before the annual closure.   Therefore, switchboard operator assistance to transfer calls from/to external lines will cease. All other phone services will run as usual.

  15. Howland Island Site 5P 3/17/2000 2-3M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Howland Island, site 5P (00 48.340 N, 176 37.272 W), between 2 and 3 meters along a permanent transect.

  16. Kingman Reef Site 5P 3/17/2002 12-13M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Kingman Reef, site 5P (6 23.805N, 162 20.941W), between 12 and 13 meters along a permanent transect.

  17. Baker Island Site 5P 3/19/2000 87-88M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Baker Island, site 5P (00 11.781N, 176 29.176W), between 87 and 88 meters along a permanent transect.

  18. Identification of miR-194-5p as a potential biomarker for postmenopausal osteoporosis.

    Science.gov (United States)

    Meng, Jia; Zhang, Dapeng; Pan, Nanan; Sun, Ning; Wang, Qiujun; Fan, Jingxue; Zhou, Ping; Zhu, Wenliang; Jiang, Lihong

    2015-01-01

    The incidence of osteoporosis is high in postmenopausal women due to altered estrogen levels and continuous calcium loss that occurs with aging. Recent studies have shown that microRNAs (miRNAs) are involved in the development of osteoporosis. These miRNAs may be used as potential biomarkers to identify women at a high risk for developing the disease. In this study, whole blood samples were collected from 48 postmenopausal Chinese women with osteopenia or osteoporosis and pooled into six groups according to individual T-scores. A miRNA microarray analysis was performed on pooled blood samples to identify potential miRNA biomarkers for postmenopausal osteoporosis. Five miRNAs (miR-130b-3p, -151a-3p, -151b, -194-5p, and -590-5p) were identified in the microarray analysis. These dysregulated miRNAs were subjected to a pathway analysis investigating whether they were involved in regulating osteoporosis-related pathways. Among them, only miR-194-5p was enriched in multiple osteoporosis-related pathways. Enhanced miR-194-5p expression in women with osteoporosis was confirmed by quantitative reverse transcription-polymerase chain reaction analysis. For external validation, a significant correlation between the expression of miR-194-5p and T-scores was found in an independent patient collection comprised of 24 postmenopausal women with normal bone mineral density, 30 postmenopausal women with osteopenia, and 32 postmenopausal women with osteoporosis (p osteoporosis.

  19. The Governance Structure, Mechanism and Strategy of Library Consortia%图书馆联盟治理的结构、机制及策略

    Institute of Scientific and Technical Information of China (English)

    刘丽萍

    2015-01-01

    文章在探究图书馆联盟治理的涵义和主要特征的基础上,对图书馆联盟治理结构模型和管理机制进行了重点分析,从政府、行业协会、图书馆、社会以及科研角度出发,提出了改进和提升图书馆联盟治理水平的对策和建议,为促进图书馆联盟治理和提高协同水平,实现可持续发展目标提供理论依据.%On the basis of the meaning and key feature of library consortia governance this paper analyzes the governance structure model and management mechanism and proposes the countermeasures and suggestions to enhance level of library consortia governance in order to promote the library consortia governance and improve the cooperative level, achieve the goal of sustainable development providing theoretical foundation from the government, industry associations, library, social and scientiifc research.

  20. Corporate governance cycles during transition

    DEFF Research Database (Denmark)

    Jones, Derek C.; Mygind, Niels

    2004-01-01

    is faster in Estonia and this can be explained by the relatively fast pace of institutional change and evolution of important gov-ernance institutions, including tough bankruptcy legislation and advances in the financial system. JEL-codes: G3, J5, P2, P3 Keywords: corporate governance, life......We begin by identifying a typical governance life-cycle, defined as changes in ownership structure, and including both the identity of the major owner and ownership concentration. The cycle is marked by key events and phases including start-up, initial growth, mature growth, and possibly a crisis...... and restructuring stage or exit stage. The governance cycle for transitional countries reflects some specific characteristics -e.g. often privatization produces specific initial ownership structures, with an unusually high proportion of insider, especially, employee ownership. Subsequently pres...

  1. Flat color TV 'FACE{sub TM}' 32Z5P; Flat color TV 'FACE{sub TM}' 32Z5P

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    A flat wide color TV, 'FACE{sub TM}' 32Z5P, was commercialized that was mounted with the 'digital million progressive circuit' in which points constituting a signal were increased to about one million. This circuit made the horizontal density to be twice in addition to the conventional vertical density, enabling more precise image expression. Further, the TV was mounted with a three-dimensional DNR (Digital Noise Reduction) circuit that reduces noise without sacrificing the picture quality, allowing the reproduction of a clean image even with the source having a lot of noise. For the purpose of coping with the diversification of an image source, the TV is equipped with two systems of D terminals which are convenient in connecting an adapter for receiving digital broadcasting for example. Furthermore, a miniaturizing design for the audio/mechanism system realized the horizontal width equivalent to that of the conventional 28 type TV. (translated by NEDO)

  2. Hot money speculation scale towards commodities and government's optimal regulation strategies%商品热钱投机规模与政府最优监管策略

    Institute of Scientific and Technical Information of China (English)

    张磊; 赵进文

    2012-01-01

    Hot money speculations have a large impact on our country' s macro - market' s operation mechanism and the stability of people' s living. In order to stabilize the price level and to regulate the market mechanism, local governments at all levels are active on establishing and implementing the regulation measures towards the hot money speculations. This paper put forward a dynamic game mechanism between the governments and the speculators, analyzed the governments' optimal regulation strategies on the equilibrium path. And discussed the inhibition effects of the government' s regulations to the speculation scale on the disequilibrium path, combined the featured of the governments regulation regime in our country nowadays. Applied the numerical stimulation methods to verify the features of the government's equilibrium regulation mechanism.%热钱的投机炒作对我国宏观市场运行机制和居民生活稳定产生了严重冲击.为稳定物价水平和规范市场机制,全国各级地方政府正在积极制定和实施对热钱投机的监管措施.构建了一个政府与投机者之间的动态博弈结构,分析了均衡路径上的政府最优监管策略,并结合我国当前的政府监管制度特点,讨论了非均衡路径上的政府监管对投机规模的抑制效应.最后采用数值模拟方法对均衡的政府监管机制的特征进行了验证.

  3. Organizational governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Klein, Peter G.

    This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory, and the ......This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory...

  4. 我国供应商与外国零售商交易冲突的博弈分析%An Analysis of the Influence of Government Action on Logistic Business Strategy

    Institute of Scientific and Technical Information of China (English)

    戴五七; 陈金龙

    2012-01-01

    This paper is about the influence of Government action on the logistic business strategy. Combining the government behavior theory and enterprise strategic theory, This paper put forward three hypotheses through logical deduction of the influence on business strategy by government action. It goes on with tructural analysis of 30 logistic enterprises using a content analysis, and the quantitative data acquired show%在厘清外国零售商与我国供应商交易冲突的内容和特点的基础上,运用完全信息博弈法,通过构建外国零售商和国内供应商的两级供应链存在性博弈模型,分析我国供应商在与外国零售商交易冲突中所处的被动地位。从数理和应用两个角度研究对策后指出:我国供应商可利用主导价格的主动合作型策略,变零供独立决策为集中决策的集中决策型策略以及建立长期的合作关系的市场交易策略,以摆脱劣势。

  5. MicroRNA-542-5p as a novel tumor suppressor in neuroblastoma.

    Science.gov (United States)

    Bray, Isabella; Tivnan, Amanda; Bryan, Kenneth; Foley, Niamh H; Watters, Karen M; Tracey, Lorraine; Davidoff, Andrew M; Stallings, Raymond L

    2011-04-01

    Several studies have implicated the dysregulation of microRNAs in neuroblastoma pathogenesis, an often fatal paediatric cancer arising from precursor cells of the sympathetic nervous system. Our group and others have demonstrated that lower expression of miR-542-5p is highly associated with poor patient survival, indicating a potential tumor suppressive function. Here, we demonstrate that ectopic over-expression of this miRNA decreases the invasive potential of neuroblastoma cell lines in vitro, along with primary tumor growth and metastases in an orthotopic mouse xenograft model, providing the first functional evidence for the involvement of miR-542-5p as a tumor suppressor in any type of cancer.

  6. Microstates of D1–D5(-P black holes, as interacting D-branes

    Directory of Open Access Journals (Sweden)

    Takeshi Morita

    2015-07-01

    Full Text Available In our previous study (Morita et al., 2014 [1], we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal. We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves. It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P black holes in superstring theory.

  7. Microstates of D1-D5(-P) black holes as interacting D-branes

    CERN Document Server

    Morita, Takeshi

    2014-01-01

    In our previous study [1] (1311.6540), we figured out that the thermodynamics of the near extremal black $p$-branes can be explained as the collective motions of gravitationally interacting elementary $p$-branes (the $p$-soup proposal). We test this proposal in the near-extremal D1-D5 and D1-D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black $p$-brane are explained in the unified picture. We also argue the relation between the $p$-soup proposal and the conformal field theory calculations of the D1-D5(-P) black holes in superstring theory.

  8. Microstates of D1-D5(-P) black holes, as interacting D-branes

    Science.gov (United States)

    Morita, Takeshi; Shiba, Shotaro

    2015-07-01

    In our previous study (Morita et al., 2014 [1]), we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal). We test this proposal in the near-extremal D1-D5 and D1-D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1-D5(-P) black holes in superstring theory.

  9. Microstates of D1–D5(-P) black holes, as interacting D-branes

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Takeshi, E-mail: morita.takeshi@shizuoka.ac.jp [Department of Physics, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan); Shiba, Shotaro, E-mail: sshiba@cc.kyoto-su.ac.jp [Maskawa Institute for Science and Culture, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555 (Japan)

    2015-07-30

    In our previous study (Morita et al., 2014 [1]), we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal). We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P) black holes in superstring theory.

  10. Corporate Governance

    Directory of Open Access Journals (Sweden)

    Dragoș-Mihail Daghie

    2011-05-01

    Full Text Available The purpose of this study is to analyze and understand the recently introduced form of managementof a company limited by shares. The Law no. 441/2006, which fundamentally amended Company Law,created this form of controlling the company, the corporate governance, but the legislation does not explicitlydefine what it wants to achieve through this instrument. This topic is recent in research as the theme ofgerman-roman commercial law systems (in French corporate governance system was introduced in 1966 andin Romania in 2006 but in terms of Anglo-Saxon law, the topic has been addressed years since 1776 (AdamSmith: The Wealth of Nations The concept of corporate governance would like, as a result, to establish somerules that companies must comply in order to achieve effective governance, transparent and beneficial forboth shareholders and for the minority. Corporate governance is a key element with an aim at improvingefficiency and economic growth in full accordance with the increase of investors’ confidence. Corporategovernance assumes a series of relationship between the company management, leadership, shareholders andthe other people concerned. Also corporate governance provides for that structure by means of which thecompany’s targets are set out and the means to achieve them and also the manner how to monitor such.

  11. Cri du chat syndrome and primary ciliary dyskinesia: a common genetic cause on chromosome 5p.

    Science.gov (United States)

    Shapiro, Adam J; Weck, Karen E; Chao, Kay C; Rosenfeld, Margaret; Nygren, Anders O H; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A

    2014-10-01

    Cri du chat syndrome (CdCS) and primary ciliary dyskinesia (PCD) are rare diseases that present with frequent respiratory symptoms. PCD can be caused by hemizygous DNAH5 mutation in combination with a 5p segmental deletion attributable to CdCS on the opposite chromosome. Chronic oto-sino-pulmonary symptoms or organ laterality defects in CdCS should prompt an evaluation for PCD.

  12. miR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lianyong; Wang, Jingnan; Li, Xiangqi; Ma, Junhua; Shi, Chao; Zhu, Hongling; Xi, Qian; Zhang, Jichen; Zhao, Xuemei; Gu, Mingjun, E-mail: mjgugonglihos@yeah.net

    2015-02-20

    microRNAs (miRNAs) are frequently dysregulated in human malignancies. It was recently shown that miR-204-5p is downregulated in papillary thyroid carcinoma (PTC); however, the functional significance of this observation is not known. This study investigated the role of miR-204-5p in PTC. Overexpressing miR-204-5p suppressed PTC cell proliferation and induced cell cycle arrest and apoptosis. The results of a luciferase reporter assay showed that miR-204-5p can directly bind to the 3′ untranslated region (UTR) of insulin-like growth factor-binding protein 5 (IGFBP5) mRNA, and IGFBP5 overexpression partially reversed the growth-inhibitory effects of miR-204-5p. These results indicate that miR-204-5p acts as a tumor suppressor in PTC by regulating IGFBP5 expression and that miR-204-5p can potentially serve as an antitumorigenic agent in the treatment of PTC. - Highlights: • miR-204-5p expression is downregulated in PTC tissues and cell lines. • miR-204-5p suppresses proliferation and promotes apoptosis in PTC cells. • miR-204-5p suppresses IGFBP5 expression by direct binding to the 3′-UTR. • IGFBP5 overexpression reverses the effects of miR-204-5p.

  13. Making Migrants Governable

    DEFF Research Database (Denmark)

    Stenum, Helle

    2012-01-01

    This paper will investigate the production of knowledge regarding the number of illegalized migrants. Estimation of the number has been the common frame for production of this kind of knowledge, performed by social scientists, government officials, NGOs and others, but now biometric technology...... by biometric technology will produce increased objectivity and depolitization in numbers of irregular migrants which could not be obtained in the field of estimation. The level of truth reflects the level of control and surveillance fixed as a strategy of government of mobility in the biometric technology....

  14. Regulation of voltage-gated potassium channels by PI(4,5)P2.

    Science.gov (United States)

    Kruse, Martin; Hammond, Gerald R V; Hille, Bertil

    2012-08-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) regulates activities of numerous ion channels including inwardly rectifying potassium (K(ir)) channels, KCNQ, TRP, and voltage-gated calcium channels. Several studies suggest that voltage-gated potassium (K(V)) channels might be regulated by PI(4,5)P(2). Wide expression of K(V) channels in different cells suggests that such regulation could have broad physiological consequences. To study regulation of K(V) channels by PI(4,5)P(2), we have coexpressed several of them in tsA-201 cells with a G protein-coupled receptor (M(1)R), a voltage-sensitive lipid 5-phosphatase (Dr-VSP), or an engineered fusion protein carrying both lipid 4-phosphatase and 5-phosphatase activity (pseudojanin). These tools deplete PI(4,5)P(2) with application of muscarinic agonists, depolarization, or rapamycin, respectively. PI(4,5)P(2) at the plasma membrane was monitored by Förster resonance energy transfer (FRET) from PH probes of PLCδ1 simultaneously with whole-cell recordings. Activation of Dr-VSP or recruitment of pseudojanin inhibited K(V)7.1, K(V)7.2/7.3, and K(ir)2.1 channel current by 90-95%. Activation of M(1)R inhibited K(V)7.2/7.3 current similarly. With these tools, we tested for potential PI(4,5)P(2) regulation of activity of K(V)1.1/K(V)β1.1, K(V)1.3, K(V)1.4, and K(V)1.5/K(V)β1.3, K(V)2.1, K(V)3.4, K(V)4.2, K(V)4.3 (with different KChIPs and DPP6-s), and hERG/KCNE2. Interestingly, we found a substantial removal of inactivation for K(V)1.1/K(V)β1.1 and K(V)3.4, resulting in up-regulation of current density upon activation of M(1)R but no changes in activity upon activating only VSP or pseudojanin. The other channels tested except possibly hERG showed no alteration in activity in any of the assays we used. In conclusion, a depletion of PI(4,5)P(2) at the plasma membrane by enzymes does not seem to influence activity of most tested K(V) channels, whereas it does strongly inhibit members of the K(V)7 and K(ir) families.

  15. Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines.

    Science.gov (United States)

    Dluzen, Douglas F; Sutliff, Aimee K; Chen, Gang; Watson, Christy J W; Ishmael, Faoud T; Lazarus, Philip

    2016-10-01

    The UDP-glucuronosyltransferase (UGT) 2B enzymes are important in the detoxification of a variety of endogenous and exogenous compounds, including many hormones, drugs, and carcinogens. Identifying novel mechanisms governing their expression is important in understanding patient-specific response to drugs and cancer risk factors. In silico prediction algorithm programs were used to screen for microRNAs (miRNAs) as potential regulators of UGT2B enzymes, with miR-216b-5p identified as a potential candidate. Luciferase data suggested the presence of a functional miR-216b-5p binding motif within the 3' untranslated regions of UGTs 2B7, 2B4, and 2B10. Overexpression of miR-216b-5p mimics significantly repressed UGT2B7 (P < 0.001) and UGT2B10 (P = 0.0018) mRNA levels in HuH-7 cells and UGT2B4 (P < 0.001) and UGT2B10 (P = 0.018) mRNA in Hep3B cells. UGT2B7 protein levels were repressed in both HuH-7 and Hep3B cells in the presence of increasing miR-216b-5p concentrations, corresponding with significant (P < 0.001 and P = 0.011, respectively) decreases in glucuronidation activity against the UGT2B7-specific substrate epirubicin. Inhibition of endogenous miR-216b-5p levels significantly increased UGT2B7 mRNA levels in HuH-7 (P = 0.021) and Hep3B (P = 0.0068) cells, and increased epirubicin glucuronidation by 85% (P = 0.057) and 50% (P = 0.012) for HuH-7 and Hep3B cells, respectively. UGT2B4 activity against codeine and UGT2B10 activity against nicotine were significantly decreased in both HuH-7 and Hep3B cells (P < 0.001 and P = 0.0048, and P = 0.017 and P = 0.043, respectively) after overexpression of miR-216b-5p mimic. This is the first evidence that miRNAs regulate UGT 2B7, 2B4, and 2B10 expression, and that miR-216b-5p regulation of UGT2B proteins may be important in regulating the metabolism of UGT2B substrates.

  16. Green governance - one solution for two problems? : climate change and economic shocks ; risk perceptions and coping strategies in China, India and Bangladesh

    OpenAIRE

    2010-01-01

    This collection of papers is based on an international workshop held in the summer of 2009 at the University of Duisburg-Essen. It brings together different perceptions regarding China, India and Bangladesh as they face the risks and crises of climate change and economic shocks like the recent global financial crisis. The papers reflect assumptions concerning the concept of Risk Society and discuss the extent to which Sustainable Development and the rather new concepts of Green Governance, Gr...

  17. Research on Pricing Strategy of the Reverse Supply Chain Considering the Government's Rewards and Punishment%考虑政府奖惩的逆向供应链定价策略研究

    Institute of Scientific and Technical Information of China (English)

    李锦飞; 刘坪; 贡文伟

    2013-01-01

    探讨一个制造商和多个零售商组成的逆向供应链定价策略问题,以再制品市场需求信息不完全为前提,运用博弈论和委托代理理论研究分析政府不参与逆向供应链运作、政府对制造商实施奖惩措施和政府对零售商实施奖惩措施三种情形下逆向供应链各主体的定价策略.并通过数值仿真验证了定价策略分别与市场需求和奖惩力度的关系.研究表明:成本较高的零售商期望收益较小;在两种奖惩力度相同的情况下,政府对制造商实施奖惩措施后逆向供应链的整体收益更大,而政府对零售商实施奖惩措施后制造商会更倾向于不传递真实市场信息的信号.%The article discusses pricing strategy problem of the reverse supply chain consisted of a manufacturer and multiple retailers.With the remade-products' market demand information incomplete as premise,using the game theory and the principal-agent theory to analyze the pricing strategy of the reverse supply chain in three situations such as when government does not participate in reverse supply chain operation,when government implements reward and punishment policy to the manufacturer and when government implements reward and punishment policy to retailers.Also,the relationship between pricing strategies and market requirements or punishment strengths is been proved through numerical simulation.The study shows that:retailers with higher cost expect less profit.Under the condition that two kinds of rewards and punishment strength is equal,when government implements rewards and punishment policy to manufacturer,the reverse supply chain obtains more overall revenue,but when government implements rewards and punishment policy to retailers,the manufacturer will have more tendency to conceal real market information signal.

  18. Discussion on the Government Network Information Security and Prevention Strategies%浅议政府机关网络信息安全及防范策略

    Institute of Scientific and Technical Information of China (English)

    樊峰鑫; 黄宇明

    2014-01-01

    伴随着全球信息一体化进程的不断加快,信息安全也开始受到多方面的威胁,同样,对于各级政府来说,网络信息化在提高政府工作效率和服务质量的同时,网络与信息安全问题也日益凸显。该文结合自身实际工作经验,针对政府信息安全问题,进行了细致的分析并提出整体安全防护策略。%With the rapid development of modern society, computer network, global information integration process accelerat-ing, information security has received many threats. For all levels of government, the network of information technology in im-proving the government efficiency and the quality of service, network and information security issues are also increasingly promi-nent. Combined with the author's own practical experience, in view of the government information security issues, a detailed analysis and put forward the overall safety recommendations.

  19. 基层政府应对社会网络舆情策略研究%Research on the Strategy of Basic-level Government to Deal with the Social Network Public Opinion

    Institute of Scientific and Technical Information of China (English)

    尹俊

    2016-01-01

    阐释社会网络舆情的内涵及基层政府应对社会网络舆情的重要性。分析目前基层政府在应对社会网络舆情上存在的主要问题。提出基层政府应对社会网络舆情的策略:更新危机管理观念,增强现代网络舆情危机意识;提高基层政府网络执政能力;提高基层政府官员网络媒介素养;构建立体化网络舆情监控长效机制;建立应对处置机制,有效控制网络舆情;完善舆情应对管理机制和保障机制。%The paper expounds the connotation of the social network public opinion,and the important role of basic-level government in dealing with social network public opinion.It analy-zes the main problems for the current basic-level government departments to deal with social network public opinion.The strategy to deal with the social network public opinion is proposed:updating the concept of crisis management to enhance the crisis consciousness of the modern network public opinion;strengthening the network governance capacity of basic-level government;improving the network media literacy of basic-level government officials;con-structing a long-term three-dimensional network public opinion monitoring mechanism;estab-lishing response mechanism to effectively control the network public opinion;perfecting the management and safeguard mechanism of public opinion response work.

  20. T-government for benefit realisation

    OpenAIRE

    2007-01-01

    This paper proposes a model for t-Government and highlights the research agenda needed to increase understanding of transformational government and the processes involved in furthering the agenda of the t-Government. In particular, both an operational and a conceptual model for the effective involvement of citizens and businesses in government functioning have been proposed. This will help to define an agenda for t-Government research that emerges from national UK strategy and ...

  1. Aviation Weapon Equipment Innovation Knowledge Governance Model and Governance Strategy%航空武器装备创新的知识治理模式及治理策略

    Institute of Scientific and Technical Information of China (English)

    郭永辉

    2015-01-01

    在系统分析航空武器装备创新知识特性的基础上,研究了集成创新下知识治理的内涵及模式。基于知识视角,分析了航空武器装备创新中的知识治理困境,提出了中心式、串联式、互通式和集成式4种知识治理模式,通过系统分析和比较,指出集成式知识治理能够较好解决航空武器装备集成创新困境。最后,针对我国航空武器装备创新困境给出了知识治理对策。%Based on the analysis of characteristics of aviation weapon equipment innovation knowledge ,studies the integrat‐ed innovation under the knowledge management connotation and management model .Aviation weapon equipment innova‐tion are analyzed based on the perspective of knowledge ,the knowledge management ,puts forward the center tandem ,in‐teroperable and integrated type ,four kinds of knowledge governance model ,through the system analysis and comparison , points out that the integrated knowledge management can better solve the aviation weapon equipment integrated innova‐tion .Finally ,in view of Chinese aviation weapon equipment innovation knowledge management countermeasures are giv‐en .

  2. MiR-15a-5p regulates viability and matrix degradation of human osteoarthritis chondrocytes via targeting VEGFA.

    Science.gov (United States)

    Chen, Hongwei; Tian, Yun

    2017-01-16

    Previous studies demonstrated that miR-15a-5p was probably associated with human hepatocellular carcinoma, while the function of miR-15a-5p in OA (Osteoarthritis) still remains unknown. Here, we uncovered the potential role of miR-15a-5p on OA pathogenesis and confirmed its predicted target VEGFA (Vascular Endothelial Growth Factor A). Measured by RT-PCR, miR-15a-5p expression increased remarkably while VEGFA expression was significantly decreased in OA chondrocytes compared with normal conditions. According to Luciferase activity assay, miR-15a-5p directly targeted the 3'-UTR of VEGFA to inhibit its expression. Functional analysis including CCK-8 assay and flow cytometry revealed that overexpression of VEGFA or inhibition of miR-15a-5p promoted cell proliferation, suppressed cell apoptosis and reduced matrix degradation in OA chondrocytes. Moreover, rescue assays carried out with both expression of VEGFA and miR-15a-5p demonstrated that miR-15a-5p contributes to cell apoptosis and matrix degradation via inhibiting VEGFA. We further provided evidence that multiple proteins related to matrix synthesis were regulated by miR-15a-5p and VEGFA using Western blot and ELISA assays. Taken together, our findings elucidated an underlying mechanism by which miR-15a-5p regulates viability and matrix degradation of OA and indicated a new target for OA diagnosis and therapy.

  3. Serum microRNA-125a-5p, a useful biomarker in liver diseases, correlates with disease progression.

    Science.gov (United States)

    Zheng, Jianjian; Zhou, Zhenxu; Xu, Ziqiang; Li, Guojun; Dong, Peihong; Chen, Zhanguo; Lin, Dezhao; Chen, Bicheng; Yu, Fujun

    2015-07-01

    It has been demonstrated that liver microRNA-125a-5p (miR-125a-5p) is correlated with disease progression in different liver diseases, including liver fibrosis and hepatocellular carcinoma (HCC). The present study investigated whether serum miR-125a-5p correlated with the progression of different liver diseases. Serum samples were obtained from healthy individuals, patients with chronic hepatitis B who had undergone a liver biopsy, and patients with HCC and were analyzed for the levels of miR-125a-5p. Compared with the healthy controls, the serum levels of miR-125a-5p were significantly higher in the liver fibrosis serum, and were reduced in HCC. With the development of liver fibrosis, there was a significant increase in the expression of miR-125a-5p (Pserum miR-125a-5p and viral replication (Pserum levels of miR-125a-5p were correlated with a poor prognosis, determined by Kaplan-Meier curve analysis (P=0.009). In the liver fibrosis and HCC groups, different expression levels of serum miR-125a-5p were observed, and were correlated with disease progression. The results of the present study suggested that serum miR-125a-5p may be used as a non-invasive biomarker for monitoring disease progression in liver diseases.

  4. Inhibition of Saccharomyces cerevisiae Pdr5p by a natural compound extracted from Brazilian Red Propolis

    Directory of Open Access Journals (Sweden)

    Cinzia Lotti

    2011-10-01

    Full Text Available Multidrug resistance of cancer cells and pathogenic microorganisms leading to the treatment failure of some forms of cancer or life-threatening bacterial or fungal infections is often caused by the overexpression of multidrug efflux pumps belonging to the ATP-binding cassette transporters superfamily. The multidrug resistance of fungal cells often involves the overexpression of efflux pumps belonging to the pleiotropic drug resistance (PDR family of ABC transporters. Possibly the best-studied fungal PDR transporter is the multidrug resistance transporter Pdr5p of Saccharomyces cerevisiae. Some research groups have been searching for new inhibitors of these efflux pumps in order to alleviate resistance. Natural products are a great source for the discovery of new compounds with biological activity. Propolis is a complex resinous material collected by honeybees from exudates and buds of certain plant sources and this material is thought to serve as a defense substance for bee hives. Propolis is widely used in traditional medicine and is reported to have a broad spectrum of pharmacological properties. Literature reported some biological functionalities of propolis, such as antibacterial, antiviral, fungicidal, anti-inflammatory and anti-carcinogenic activities. The chemical composition of propolis is qualitatively and quantitatively variable. Components isolated from methanolic extract of red Brazilian propolis (Alagoas, Northeast of Brazil are isoflavonoids (including pterocarpans, isoflavans, isoflavones, flavanones and polyprenylated benzophenones. In this work we demonstrated the effects of five different isolated compounds on the ATPase activity of Pdr5p. Out of all five substances tested, only BRP-1 was able to completely abolish the enzymatic activity while others worked as positive modulators of the enzyme activity. BRP-1also inhibited the efflux of Rhodamine 6G from yeast cells overexpressing Pdr5p. Taken together, these results

  5. Military Government

    Science.gov (United States)

    1949-07-01

    Public finance -------------------~·---------------------22 Civilian protection -------------------------------------23 Public health and sanitation...22. PUBLIC. ~INANCE.~q. Basic "planning data for public finance in- clude-- (1) ·rrax·ation systems: - .(2)- ~ethods of_tpaking appropriations.- ( 3...Probable ·adequacy- of public funds. (.4) Administrative .. _ organization for_ public finance sections. b. Military government -staff sections

  6. Small government or big government?

    Directory of Open Access Journals (Sweden)

    MATEO SPAHO

    2015-03-01

    Full Text Available Since the beginning of the twentieth century, economists and philosophers were polarizedon their positions beyond the role that the government should have in the economy. On one hand John Maynard Keynes represented, within the optics of market economy, a position where the state should intervene in the economy to maintain the aggregate demand and the employment in the country, without hesitation in creating budget deficits and public debt expansion. This approach happens especially in the moments when the domestic economy and global economic trends show a weak growth or a recession. This means a heavy interference inthe economy, with higher income but with high expenditure to GDP too. On the other side, Liberals and Neoliberalsled by Friedrich Hayek advocated a withdrawal of the government from economic activity not just in moments of economic growth but also during the crisis, believing that the market has self-regulating mechanisms within itself. The government, as a result will have a smaller dimension with lower income and also low expenditures compared to the GDP of the country. We took the South-Eastern Europe countries distinguishing those with a "Big Government" or countries with "Small Government". There are analyzed the economic performances during the global crisis (2007-2014. In which countries the public debt grew less? Which country managed to attract more investments and which were the countries that preserved the purchasing power of their consumers? We shall see if during the economic crisis in Eastern Europe the Great Government or the Liberal and "Small" one has been the most successful the model.

  7. Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

    Directory of Open Access Journals (Sweden)

    Julien Robert-Paganin

    Full Text Available FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686: one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

  8. Local Government Internal Audit Compliance

    Directory of Open Access Journals (Sweden)

    Greg Jones

    2015-09-01

    Full Text Available Local government councils (LGC rely on a number of funding sources including state and federal governments as well as their community constituents to enable them to provide a range of public services. Given the constraints on these funding sources councils need to have in place a range of strategies and policies capable of providing good governance and must appropriately discharge their financial accountabilities. To assist LGC with meeting their governance and accountability obligations they often seek guidance from their key stakeholders. For example, in the Australian State of New South Wales (NSW, the Office of Local Government has developed a set of guidelines, the Internal Audit Guidelines. In 2010 the NSW Office of Local Government issued revised guidelines emphasising that an internal audit committee is an essential component of good governance. In addition, the guidelines explained that to improve the governance and accountability of the councils, these committees should be composed of a majority of independent members. To maintain committee independence the guidelines indicated that the Mayor should not be a member of the committee. However these are only guidelines, not legislated requirements and as such compliance with the guidelines, before they were revised, has been demonstrated to be quite low (Jones & Bowrey 2013. This study, based on a review of NSW Local Government Councils’ 2012/2013 reports, including Annual Reportsrelation to internal audit committees, to determine if the guidelines are effective in improving local government council governance.

  9. Bogotá experience in government: device and educational strategies to expressions, scenarios and breaks on a proposal for citizen culture

    Directory of Open Access Journals (Sweden)

    Gloria Clemencia VALENCIA GONZÁLEZ

    2012-05-01

    Full Text Available The Bogotá currently known, rebuilt from the ashes of 9 April got used for decades to live labors, fear and mistrust, but particularly in exclusion. With the arrival of Antanas Mockus to Mayor broke various paradigms: he and his cabinet not came from the traditional political caste, came from the Academy and claimed other relationships with citizenship. In addition, became the city learning space because their Government project drew on the political but evidenced in the pedagogical and found its deployment in the communicative. Six priorities proposed for government experience are articulated around one: civic culture. Culture that should be disseminated, learned and implementation from train in town, then so is generate sense of belonging, would facilitate urban coexistence and would lead to the respect of the common heritage and recognition of the rights and duties of citizens. In the Mayor Mockus’s «great classroom» citizenship would of apathy to the habitancia. Far pedagogy and communication, as not nominated devices, managed to go beyond the labelling and the indication and approached the civic culture to political socialization? This reflection article links to research «higher education and training citizen, case Bogotá» and consists of five sections.

  10. miR-487b-5p Regulates Temozolomide Resistance of Lung Cancer Cells Through LAMP2-Medicated Autophagy.

    Science.gov (United States)

    Bao, Liang; Lv, Lei; Feng, Jinping; Chen, Yuyu; Wang, Xinhua; Han, Shuguang; Zhao, Hongqing

    2016-08-01

    Temozolomide (TMZ) is a standard agent used in the treatment of various types of cancers, including lung carcinoma, but TMZ resistance is common and accounts for many treatment failures. We investigated miRNA-487b-5p (miR-487b-5p) was highly expressed in A549 and H1299 cells which acquired TMZ resistance. Suppression of miR-487b-5p had overt effects on cellular proliferation and migration in the presence of TMZ. On the other hand, knockdown of miR-487b-5p resulted in increased survival and moderate tumor growth in vivo. In addition, the decreased cellular proliferation following miR-487b-5p suppression was linked to enhanced autophagy, evident by drastically increased levels of LC3-II, BECLIN1, and LAMP2 when miR-487b-5p was knocked down. Further analysis revealed that LAMP2 might be the target gene of miR-487b-5p. In conclusion, our study suggested that miR-487b-5p may be a potential biomarker of acquired TMZ resistance in lung cancer cells, and miR-487b-5p inhibition can be further explored as a chemotherapy target in the treatment of TMZ-resistant lung carcinoma.

  11. Mobilizing Government

    DEFF Research Database (Denmark)

    Wang, Cancan; Medaglia, Rony; Jensen, Tina Blegind

    2016-01-01

    The nature of inter-organizational collaboration between government and other stakeholders is rapidly changing with the introduction of open social media (OSM) platforms. Characterized by a high degree of informality as well as a blurred personal/professional nature, OSM can potentially introduce...... changes and tensions in the well-established routines of the public sector. This paper aims at shedding light on such changes, presenting findings from a study on the use of an OSM platform, WeChat, in an interorganizational collaboration project between government, university, and industry stakeholders...... in the four dimensions of time, task, team, and transition. Specifically, we report on new collaboration procedures that are characterized by an ad-hoc and non-linear management of time; a sense of shared commitment to the accomplishment of tasks; a serendipitous recruitment of team members based on expertise...

  12. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Hansen, Jesper Rosenberg; Villadsen, Anders Ryom

    We suggest that both making and buying the same product or service has several effects on market performance. A model is developed and tested by use of 170 answers gathered from the Danish municipalities. The results support the hypotheses that both making and buying: (1) moderates the negative r...... on how the plurality is measured. The results indicate that internal production may facilitate effective governance of the relationships with suppliers. Implications for research on firm boundaries and for practice are also discussed....

  13. 论政府责任与残疾人就业促进保障策略%Government Responsibility an Strategy in Promoting the Disable’s Employment

    Institute of Scientific and Technical Information of China (English)

    姜竹

    2012-01-01

      残疾人失业问题是我国转型期以及后危机时期面临的最严峻挑战之一。在应对这个挑战的过程中,政府的战略选择经历了一个重要的转变。从最初实行再就业工程,逐渐过渡到采取“再就业”、“失业保障”等多管齐下的策略,来应对严峻而复杂的残疾人就业形势。可见,升级公共就业服务能力的同时健全残疾人就业保障体系将是我国经济社会和谐发展的重要任务之一。结合残疾人所面临的就业压力及制约就业的因素,应当彰显政府责任,激发社会资源共同创建“灵活性”与“安全性”并行的就业格局是实现残疾人就业促进目标的必然选择,为此,完善政府相关就业保障策略是十分必要的。%  The unemployment problem is one of the most serious challenges in China in transition and post-crisis period. Therefore, the government's strategic choice has undergone a major transformation:from the initial implementation of re-employment project, a gradual transition to adopt a“re-employment”and “social protection against unemployment”, two-pronged approach to deal with severe and complex employment situation. It’s thus clear that upgrading public employment capacity and services and employment security system will be an important task of China's economic and social development. By summing up the international experience and analysis of the employment pressure facing with China, the authors believed that it’s the inevitable choice to reaffirm government's responsibility to create a employment pattern with “flexibility” and “security”. It’s necessary to reform government-related employment security policy.

  14. CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Dan Alexandru SITARU

    2009-10-01

    Full Text Available The work is aimed to examine the issues “corporate governance” involves, with the goal set to clarify the meanings of such notion, and to provide an overall image of the positive effects arising implementing the corporate governance principles. The first section includes a series of definitions for the purpose of explaining and outlining the concept of “corporate governance”, subsequently giving a definition that appears adequate to us, from the legal standpoint pre eminently. The second section has for purpose to state the corporate governance Principles, and briefly examine the same. Its purpose also includes concretely illustrating the efficient operation methods for a “corporation”, as well as the main dilemmas, and the existing solutions for the same within the internal structure of a joint stock company to adopt, and subject itself to, such principles. Finally, the last section of the work underlines the corporate governance importance, and states the goals to be attained for purposes of securing effective, balanced, and not in the last place profitable management.

  15. Activity-dependent PI(3,5)P2 synthesis controls AMPA receptor trafficking during synaptic depression.

    Science.gov (United States)

    McCartney, Amber J; Zolov, Sergey N; Kauffman, Emily J; Zhang, Yanling; Strunk, Bethany S; Weisman, Lois S; Sutton, Michael A

    2014-11-11

    Dynamic regulation of phosphoinositide lipids (PIPs) is crucial for diverse cellular functions, and, in neurons, PIPs regulate membrane trafficking events that control synapse function. Neurons are particularly sensitive to the levels of the low abundant PIP, phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], because mutations in PI(3,5)P2-related genes are implicated in multiple neurological disorders, including epilepsy, severe neuropathy, and neurodegeneration. Despite the importance of PI(3,5)P2 for neural function, surprisingly little is known about this signaling lipid in neurons, or any cell type. Notably, the mammalian homolog of yeast vacuole segregation mutant (Vac14), a scaffold for the PI(3,5)P2 synthesis complex, is concentrated at excitatory synapses, suggesting a potential role for PI(3,5)P2 in controlling synapse function and/or plasticity. PI(3,5)P2 is generated from phosphatidylinositol 3-phosphate (PI3P) by the lipid kinase PI3P 5-kinase (PIKfyve). Here, we present methods to measure and control PI(3,5)P2 synthesis in hippocampal neurons and show that changes in neural activity dynamically regulate the levels of multiple PIPs, with PI(3,5)P2 being among the most dynamic. The levels of PI(3,5)P2 in neurons increased during two distinct forms of synaptic depression, and inhibition of PIKfyve activity prevented or reversed induction of synaptic weakening. Moreover, altering neuronal PI(3,5)P2 levels was sufficient to regulate synaptic strength bidirectionally, with enhanced synaptic function accompanying loss of PI(3,5)P2 and reduced synaptic strength following increased PI(3,5)P2 levels. Finally, inhibiting PI(3,5)P2 synthesis alters endocytosis and recycling of AMPA-type glutamate receptors (AMPARs), implicating PI(3,5)P2 dynamics in AMPAR trafficking. Together, these data identify PI(3,5)P2-dependent signaling as a regulatory pathway that is critical for activity-dependent changes in synapse strength.

  16. Holographic description of non-supersymmetric orbifolded D1-D5-P solutions

    CERN Document Server

    Chakrabarty, Bidisha; Virmani, Amitabh

    2015-01-01

    Non-supersymmetric black hole microstates are of great interest in the context of the black hole information paradox. We identify the holographic description of the general class of non-supersymmetric orbifolded D1-D5-P supergravity solutions found by Jejjala, Madden, Ross and Titchener. This class includes both completely smooth solutions and solutions with conical defects, and in the near-decoupling limit these solutions describe degrees of freedom in the cap region. The CFT description involves a general class of states obtained by fractional spectral flow in both left-moving and right-moving sectors, generalizing previous work which studied special cases in this class. We compute the massless scalar emission spectrum and emission rates in both gravity and CFT and find perfect agreement, thereby providing strong evidence for our proposed identification. We also investigate the physics of ergoregion emission as pair creation for these orbifolded solutions. Our results represent the largest class of non-supe...

  17. Smooth non-extremal D1-D5-P solutions as charged gravitational instantons

    CERN Document Server

    Chakrabarty, Bidisha; Virmani, Amitabh

    2016-01-01

    We present an alternative and more direct construction of the non-supersymmetric D1-D5-P supergravity solutions found by Jejjala, Madden, Ross and Titchener. We show that these solutions --- with all three charges and both rotations turned on --- can be viewed as a charged version of the Myers-Perry instanton. We present an inverse scattering construction of the Myers-Perry instanton metric in Euclidean five-dimensional gravity. The angular momentum bounds in this construction turn out to be precisely the ones necessary for the smooth microstate geometries. We add charges on the Myers-Perry instanton using appropriate SO(4,4) hidden symmetry transformations. The full construction can be viewed as an extension and simplification of a previous work by Katsimpouri, Kleinschmidt and Virmani.

  18. Electric-dipole 5s - 5p Transitions in Promethiumlike Ions

    Energy Technology Data Exchange (ETDEWEB)

    Vilkas, M J; Ishikawa, Y; Trabert, E

    2008-02-29

    The 5s-5p electric-dipole resonance transitions in highly ionized promethiumlike ions have been studied applying relativistic multi-reference Moeller-Plesset second-order perturbation theory. The transition wavelengths are determined to within 0.2 {angstrom} in the more highly charged ions, where the level degeneracies are small. For somewhat lighter ions a very large reference space was used in order to account for the many degeneracies. In order to calculate transition probabilities and lifetimes, correlation corrections have been added to the transition operator in the next order. The contributions from the higher orders of the theory, that is, frequency-dependent Breit correction, Lamb shift, and mass shifts, have been estimated. The results are used to re-assess spectroscopic data from beam-foil, electron beam ion trap, and tokamak observations.

  19. Sua5p is required for telomere recombination in Saccharomyces cerevisiae

    Institute of Scientific and Technical Information of China (English)

    Fei-Long Meng; Xiao-Fen Chen; Yan Hu; Hong-Bo Tang; Wei Dang; Jin-Qiu Zhou

    2010-01-01

    @@ Dear Editor, Telomeres are highly organized DNA-protein struc-tures at the ends of linear eukaryotic chromosomes [1]. In budding yeast Saccharomyces cerevisiae, each chro-mosome end has TG_(1-3)/C_(1-3)A double-stranded telomeric DNA and a G-rich single-stranded tail [2]. The replica-tion of telomere involves both telomerase and recombi-nation pathways [3, 4]. When telomerase is absent, te-lomeric DNA will progressively shorten, and the colony will eventually undergo senescence [4]. Some survivors will escape senescence by maintaining telomeres through a Rad52-dependent homologous recombination mecha-nism [3]. Our previous work had identified a conserved non-OB-fold single-stranded telomeric (ssTG) DNA binding protein Sua5p, which facilitates telomerase ac-tivity [5].

  20. Using glycosaminoglycan/chemokine interactions for the long-term delivery of 5P12-RANTES in HIV prevention.

    Science.gov (United States)

    Wang, Nick X; Sieg, Scott F; Lederman, Michael M; Offord, Robin E; Hartley, Oliver; von Recum, Horst A

    2013-10-07

    5P12-RANTES is a recently developed chemokine analogue that has shown high level protection from SHIV infection in macaques. However, the feasibility of using 5P12-RANTES as a long-term HIV prevention agent has not been explored partially due to the lack of available delivery devices that can easily be modified for long-term release profiles. Glycosaminoglycans (GAGs) have been known for their affinity for various cytokines and chemokines, including native RANTES, or CCL5. In this work, we investigated used of GAGs in generating a chemokine drug delivery device. Initial studies used surface plasmon resonance analysis to characterize and compare the affinities of different GAGs to 5P12-RANTES. These different GAGs were then incorporated into drug delivery polymeric hydrogels to engineer sustained release of the chemokines. In vitro release studies of 5P12-RANTES from the resulting polymers were performed, and we found that 5P12-RANTES release from these polymers can be controlled by the amount and type of GAG incorporated. Polymer disks containing GAGs with stronger affinity to 5P12-RANTES resulted in more sustained and longer term release than did polymer disks containing GAGs with weaker 5P12-RANTES affinity. Similar trends were observed by varying the amount of GAGs incorporated into the delivery system. 5P12-RANTES released from these polymers demonstrated good levels of CCR5 blocking, retaining activity even after 30 days of incubation.

  1. PtdIns(3,4,5)P3 is a regulator of myosin-X localization and filopodia formation

    DEFF Research Database (Denmark)

    Plantard, Laure; Arjonen, Antti; Lock, John G

    2010-01-01

    Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] is a key regulator of cell signaling that acts by recruiting proteins to the cell membrane, such as at the leading edge during cell migration. Here, we show that PtdIns (3,4,5)P3 plays a central role in filopodia formation via the bindi...

  2. New EMBO members' review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts.

    Science.gov (United States)

    Caroni, P

    2001-08-15

    The phosphoinositide lipid PI(4,5)P(2) is now established as a key cofactor in signaling to the actin cytoskeleton and in vesicle trafficking. PI(4,5)P(2) accumulates at membrane rafts and promotes local co-recruitment and activation of specific signaling components at the cell membrane. PI(4,5)P(2) rafts may thus be platforms for local regulation of morphogenetic activity at the cell membrane. Raft PI(4,5)P(2) is regulated by lipid kinases (PI5-kinases) and lipid phosphatases (e.g. synaptojanin). In addition, GAP43-like proteins have recently emerged as a group of PI(4,5)P(2) raft-modulating proteins. These locally abundant proteins accumulate at inner leaflet plasmalemmal rafts where they bind to and co-distribute with PI(4,5)P(2), and promote actin cytoskeleton accumulation and dynamics. In keeping with their proposed role as positive modulators of PI(4,5)P(2) raft function, GAP43-like proteins confer competence for regulated morphogenetic activity on cells that express them. Their function has been investigated extensively in the nervous system, where their expression promotes neurite outgrowth, anatomical plasticity and nerve regeneration. Extrinsic signals and intrinsic factors may thus converge to modulate PI(4,5)P(2) rafts, upstream of regulated activity at the cell surface.

  3. Synaptic PI(3,4,5)P3 Is Required for Syntaxin1A Clustering and Neurotransmitter Release

    NARCIS (Netherlands)

    Khuong, T.M.; Habets, R.L.; Kuenen, S.; Witkowska, A.; Kasprowicz, J.; Swerts, J.; Jahn, R.; Bogaart, G. van den; Verstreken, P.

    2013-01-01

    PI(3,4,5)P3 is a low-abundance lipid thought to play a role in the regulation of synaptic activity; however, the mechanism remains obscure. We have constructed novel split Venus-based probes and used superresolution imaging to localize PI(3,4,5)P3 at Drosophila larval neuromuscular synapses. We find

  4. miR-3940-5p enhances homologous recombination after DSB in Cr(VI) exposed 16HBE cell.

    Science.gov (United States)

    Li, Yang; Hu, Guiping; Li, Ping; Tang, Shichuan; Zhang, Ji; Jia, Guang

    2016-02-17

    Hexavalent chromium (Cr(VI)) is a well-recognized human carcinogen, yet the molecular mechanisms by which cause human cancer are still not well understood. MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in carcinogenesis and DNA damage repair. Previous occupational population study showed that hexavalent chromium (Cr(VI)) downregulated plasma miR-3940-5p level, and a low miR-3940-5p level was associated with high XRCC2 expression in lymphocytes, indicating that miR-3940-5p maybe play a protective effect in Cr(VI) induced DNA damage. Here we investigated miR-3940-5p expression and its roles in DNA repair in Cr(VI)-treated 16HBE cells. miR-3940-5p change was detected by qRT-PCR. Rad51 foci formation and double strand break (DSB) were investigated to assess homologous recombination repair (HR) capacity by Immunofluorescent assay and Neutral Comet assay. XRCC2 expression was also evaluated after miRNA oligonucleotides transfection using Western blot. Cr(VI) treatment suppressed miR-3940-5p level in 16HBE cells. miR-3904-5p mimic downregulated XRCC2 expression. As a result, the formation of Rad51-foci was inhibited and DSB repair was prolonged. The results indicate that miR-3940-5p plays a protective effect in Cr(VI) induced DNA damage.

  5. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Saunders, Edward J; Leongamornlert, Daniel A

    2013-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that...

  6. Insights into the molecular recognition of the granuphilin C2A domain with PI(4,5)P2.

    Science.gov (United States)

    Wan, Chanjuan; Wu, Bo; Song, Zhenwei; Zhang, Jiahai; Chu, Huiying; Wang, Aoli; Liu, Qingsong; Shi, Yunyu; Li, Guohui; Wang, Junfeng

    2015-02-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a key player in regulating the process of excytosis, including insulin secretion. Granuphilin, a tandem C2 domain containing protein, mediates the docking of insulin granules onto plasma membrane. The C2A domain plays key roles in this process through interaction with PI(4,5)P2. In this study, we have investigated the molecular recognition mechanism of granuphilin-C2A domain to PI(4,5)P2 head group, and further to PI(4,5)P2-nanodisc by NMR, ITC, MST and SEC methods. Our results demonstrate that PI(4,5)P2 binds to the concave surface of granuphilin-C2A domain. The key residues involved in the binding were validated by mutation analysis.

  7. Research on the relation between the knowledge governance mechanism and the strategy orientation%知识治理机制和战略导向的关系研究

    Institute of Scientific and Technical Information of China (English)

    陈俊; 王影

    2013-01-01

    在认同知识治理的本质是对知识活动所涉主体行为的协调这一基础上,归纳和分析官僚控制、社区自治、市场调节三类典型的知识治理机制的总体特征;同时,基于顾客导向、创新导向的战略导向分类,以不同战略导向匹配相异的知识治理机制组合权重为切入点,提出环境变动、知识活动障碍是企业战略导向、知识治理机制、知识活动之间演进关系的内在机理;最后,总结分析两条典型的演进路径,并指出顾客知识、治理经验的累积是演进关系螺旋上升的源动力。%On the basis of the fact that the essence of knowledge governance is to coordinate the behavior of knowledge sub -jects related to the knowledge activity , we analyze the general feature of hierarchy control、 communication autonomy、 mar-ket transaction by means of theory induction.At the same time , in this paper , the variation of environment and the barrier of knowledge activity are the inner cause of the evolutionary relation between strategy orientation 、 knowledge governance mechanism and knowledge activity if the different strategy , which includes customer orientation and innovation orientation , match the different combined weight of the governance mechanisms.Finally, two typical evolutionary paths are generated in this paper.And the original dynamic leading to the upward spiral of evolutionary relation lies in the accumulation of custom -er knowledge and governance experience.

  8. MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Jian; Xiao, Gelei [Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008 (China); Peng, Gang [Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Liu, Dingyang [Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008 (China); Wang, Zeyou [Cancer Research Institute, Central South University, Changsha, Hunan 410008 (China); Liao, Yiwei; Liu, Qing [Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008 (China); Wu, Minghua [The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008 (China); Cancer Research Institute, Central South University, Changsha, Hunan 410008 (China); Yuan, Xianrui, E-mail: xry69@163.com [Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008 (China)

    2015-02-06

    Highlights: • Expression of miR-125a-5p is inversely correlated with that of TAZ in glioma cells. • MiR-125a-5p represses TAZ expression in glioma cells. • MiR-125a-5p directly targets the 3′ UTR of TAZ mRNA and promotes its degradation. • MiR-125a-5p represses CTGF and survivin via TAZ, and inhibits glioma cell growth. • MiR-125a-5p inhibits the stem cell features of HFU-251 MG cells. - Abstract: Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3′ UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.

  9. hsa-miR-125a-5p Enhances Invasion Ability in Non-Small Lung Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Enhua WANG

    2009-09-01

    Full Text Available Background and objective MicroRNAs (miRNAs are short non-coding RNAs that posttranscriptionally regulate gene expression by partially binding complementary to target sites in mRNAs. Although some impaired miRNA regulations have been observed in many human cancers, the functions of miR-125a are still unclear. The aim of this study is to investigate the expression of hsa-miR-125a-5p in NSCLC cell lines and the relationship between hsa-miR-125a-5p and the invasion of lung cancer cells. Methods The expression of hsa-miR-125a-5p and the effectiveness for a given period time after being transfected sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide, which were 24 h, 36 h, 48 h, 60 h and 72 h, were examined by realtime PCR. Meanwhile, we investigated the modification of invasive ability in A549 and NCI-H460 cells by transwell. Results Real-time PCR showed that hsa-miR-125a-5p was poorly-expressed in 6 lung cancer cell lines, especially in LH7, NCI-H460, SPC-A-1 and A549. The highest expression of hsa-miR-125a-5p occurred in the cells transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide 36 h. Furthermore, the invasive abilities of A549 and NCI-H46O were enhanced by up-regulating hsa-miR-125a-5p. Conclusion hsa-miR-125a-5p was poorly-expressed in lung cancer cells and it could enhance lung cancer cell invasion by up-regulating hsa-miR-125a-5p.

  10. Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating.

    Science.gov (United States)

    Maléth, Jozsef; Choi, Seok; Muallem, Shmuel; Ahuja, Malini

    2014-12-17

    The Orai1-STIM1 current undergoes slow Ca(2+)-dependent inactivation (SCDI) mediated by the binding of SARAF to STIM1. Here we report the use of SCDI by SARAF as a probe of the conformation and microdomain localization of the Orai1-STIM1 complex. We find that the interaction of STIM1 with Orai1 carboxyl terminus (C terminus) and the STIM1 K-domain are required for the interaction of SARAF with STIM1 and SCDI. STIM1-Orai1 must be in a PM/ER microdomain tethered by E-Syt1, stabilized by septin4 and enriched in PI(4,5)P2 for STIM1-SARAF interaction. Targeting STIM1 to PI(4,5)P2-rich and -poor microdomains reveals that SARAF-dependent SCDI is observed only when STIM1-Orai1 are within the PI(4,5)P2-rich microdomain. Notably, store depletion results in transient localization of STIM1-Orai1 in the PI(4,5)P2-poor microdomain, which then translocates to the PI(4,5)P2-rich domain. These findings reveal the role of PM/ER tethers in the regulation of Orai1 function and a mode of regulation by PI(4,5)P2 involving translocation between PI(4,5)P2 microdomains.

  11. Visualization of Ins(1,4,5)P3 dynamics in living cells: two distinct pathways for Ins(1,4,5)P3 generation following mechanical stimulation of HSY-EA1 cells.

    Science.gov (United States)

    Nezu, Akihiro; Tanimura, Akihiko; Morita, Takao; Tojyo, Yosuke

    2010-07-01

    In the present study, the contribution of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] generation on the mechanical-stimulation-induced Ca(2+) response was investigated in HSY-EA1 cells. Mechanical stimulation induced a local increase in the cytosolic concentration of Ins(1,4,5)P(3) ([IP(3)](i)), as indicated by the Ins(1,4,5)P(3) biosensor LIBRAvIII. The area of this increase expanded like an intracellular Ins(1,4,5)P(3) wave as [IP(3)](i) increased in the stimulated region. A small transient [IP(3)](i) increase was subsequently seen in neighboring cells. The phospholipase C inhibitor U-73122 abolished these Ins(1,4,5)P(3) responses and resultant Ca(2+) releases. The purinergic receptor blocker suramin completely blocked increases in [IP(3)](1) and the Ca(2+) release in neighboring cells, but failed to attenuate the responses in mechanically stimulated cells. These results indicate that generation of Ins(1,4,5)P(3) in response to mechanical stimulation is primarily independent of extracellular ATP. The speed of the mechanical-stimulation-induced [IP(3)](i) increase was much more rapid than that induced by a supramaximal concentration of ATP (1 mM). The contribution of the Ins(1,4,5)P(3)-induced Ca(2+) release was larger than that of Ca(2+) entry in the Ca(2+) response to mechanical stimulation in HSY-EA1 cells.

  12. Government Construction Safety Supervision and Strategies Game%政府建筑安全监管博弈分析及策略选择

    Institute of Scientific and Technical Information of China (English)

    陈宝春

    2011-01-01

    建筑安全事故的频繁发生已严重制约着和谐社会的构建和建筑业的健康发展.基于博弈论原理,从政府监管机构、承包商、监理三个安全责任主体利益考虑,构建了监管机构与承包商、监管机构与监理的博弈模型,分析了建筑安全事故产生的本质原因,并提出了安全监管的应对措施,以降低建筑安全事故的发生.%The frequent occurrence of accidents in censtruction has seriously restricted the construction of harmonious society and the healthy development of the construction industry.Based on the game theory, from the government regulatory agencies, contractors, supervision of the security responsibility of the three main interests, the paper builds regulatory agencies and contractors, regulatory agencies and supervision of the game model to analyze the construction safety accidents of nature, and puts forward security control measures in order to lower construction safety accidents.

  13. Strategi Pemberdayaan Perusahaan Waralaba Lokal Menuju Waralaba Global: Studi Kasus Good Corporate Governance oleh Eksekutif Puncak di J.Co, Es Teller 77, dan Pecel Lele Lela

    Directory of Open Access Journals (Sweden)

    Lelo Yosep Laurentius

    2015-08-01

    Full Text Available This research is mainly intended for reviewing and strengthening leadership, corporate governance good practices and management philosophy in the concepts, systems, and human resources (HR of the company. A new progressive corporate leader should be able to quickly identify the strengths and weaknesses of his/her business, to increase the first and to reduce the pressures or to liquidate the later. Finally, he/she must be able to encourage his/her subordinates to achieve easily identified and highly attractive goals. The target is to build the 21st-century company where all employees realize that they can make it different and that they will warmly welcome the managerial motivation. Thus, the chief executive officer assumes the responsibility for constructive managerial skills. Research used qualitative approach to disclose GCG in local franchise companies. Case study was done purposively with chief executive officer of the company. Data were gathered by observation and literature study. Analysis was conducted by data reduction, data presentation, and conclusion.

  14. Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells.

    Science.gov (United States)

    Kong, Lu; Hao, Qi; Wang, Ying; Zhou, Ping; Zou, Binbin; Zhang, Yu-xiang

    2015-09-29

    nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays a tumor-suppressive role in a wide range of cancer cells through its activity as a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by sequencing stem-PCR products, we found that a microRNA originating from this precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The expression levels of the predicted targets of VTRNA2-1-5p are negatively correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues. Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has oncogenic activity related to the progression of cervical cancer. Here, we report that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion, proliferation, and tumorigenicity while increasing apoptosis and p53 expression. Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53 expression and high VTRNA2-1-5p expression were positively associated.In addition, VTRNA2-1-5p was found to directly target the 5' and 3' untranslated regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53 and suggest that it plays an essential role in the apoptosis and proliferation of cervical cancer cells.

  15. Evaluating the ability of artificial neural network and PCA-M5P models in predicting leachate COD load in landfills.

    Science.gov (United States)

    Azadi, Sama; Amiri, Hamid; Rakhshandehroo, G Reza

    2016-09-01

    Waste burial in uncontrolled landfills can cause serious environmental damages and unpleasant consequences. Leachates produced in landfills have the potential to contaminate soil and groundwater resources. Leachate management is one of the major issues with respect to landfills environmental impacts. Improper design of landfills can lead to leachate spread in the environment, and hence, engineered landfills are required to have leachate monitoring programs. The high cost of such programs may be greatly reduced and cost efficiency of the program may be optimized if one can predict leachate contamination level and foresee management and treatment strategies. The aim of this study is to develop two expert systems consisting of Artificial Neural Network (ANN) and Principal Component Analysis-M5P (PCA-M5P) models to predict Chemical Oxygen Demand (COD) load in leachates produced in lab-scale landfills. Measured data from three landfill lysimeters, including rainfall depth, number of days after waste deposition, thickness of top and bottom Compacted Clay Liners (CCLs), and thickness of top cover over the lysimeter, were utilized to develop, train, validate, and test the expert systems and predict the leachate COD load. Statistical analysis of the prediction results showed that both models possess good prediction ability with a slight superiority for ANN over PCA-M5P. Based on test datasets, the mean absolute percentage error for ANN and PCA-M5P models were 4% and 12%, respectively, and the correlation coefficient for both models was greater than 0.98. Developed models may be used as a rough estimate for leachate COD load prediction in primary landfill designs, where the effect of a top and/or bottom liner is disputed.

  16. PU.1 Is Identified as a Novel Metastasis Suppressor in Hepatocellular Carcinoma Regulating the miR-615-5p/IGF2 Axis.

    Science.gov (United States)

    Song, Li-Jie; Zhang, Wei-Jie; Chang, Zhi-Wei; Pan, Yan-Feng; Zong, Hong; Fan, Qing-Xia; Wang, Liu-Xing

    2015-01-01

    Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

  17. Molecular Recognition of PTS-1 Cargo Proteins by Pex5p: Implications for Protein Mistargeting in Primary Hyperoxaluria

    Directory of Open Access Journals (Sweden)

    Noel Mesa-Torres

    2015-02-01

    Full Text Available Peroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1, where alanine:glyoxylate aminotransferase (AGT undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3–4 orders of magnitude reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.

  18. PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility.

    Science.gov (United States)

    Golub, Tamara; Caroni, Pico

    2005-04-11

    The lipid second messenger PI(4,5)P(2) modulates actin dynamics, and its local accumulation at plasmalemmal microdomains (rafts) might mediate regulation of protrusive motility. However, how PI(4,5)P(2)-rich rafts regulate surface motility is not well understood. Here, we show that upon signals promoting cell surface motility, PI(4,5)P(2) directs the assembly of dynamic raft-rich plasmalemmal patches, which promote and sustain protrusive motility. The accumulation of PI(4,5)P(2) at rafts, together with Cdc42, promotes patch assembly through N-WASP. The patches exhibit locally regulated PI(4,5)P(2) turnover and reduced diffusion-mediated exchange with their environment. Patches capture microtubules (MTs) through patch IQGAP1, to stabilize MTs at the leading edge. Captured MTs in turn deliver PKA to patches to promote patch clustering through further PI(4,5)P(2) accumulation in response to cAMP. Patch clustering restricts, spatially confines, and polarizes protrusive motility. Thus, PI(4,5)P(2)-dependent raft-rich patches enhance local signaling for motility, and their assembly into clusters is regulated through captured MTs and PKA, coupling local regulation of motility to cell polarity, and organization.

  19. MiR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma.

    Science.gov (United States)

    Liu, Lianyong; Wang, Jingnan; Li, Xiangqi; Ma, Junhua; Shi, Chao; Zhu, Hongling; Xi, Qian; Zhang, Jichen; Zhao, Xuemei; Gu, Mingjun

    2015-02-20

    microRNAs (miRNAs) are frequently dysregulated in human malignancies. It was recently shown that miR-204-5p is downregulated in papillary thyroid carcinoma (PTC); however, the functional significance of this observation is not known. This study investigated the role of miR-204-5p in PTC. Overexpressing miR-204-5p suppressed PTC cell proliferation and induced cell cycle arrest and apoptosis. The results of a luciferase reporter assay showed that miR-204-5p can directly bind to the 3' untranslated region (UTR) of insulin-like growth factor-binding protein 5 (IGFBP5) mRNA, and IGFBP5 overexpression partially reversed the growth-inhibitory effects of miR-204-5p. These results indicate that miR-204-5p acts as a tumor suppressor in PTC by regulating IGFBP5 expression and that miR-204-5p can potentially serve as an antitumorigenic agent in the treatment of PTC.

  20. Synaptic PI(3,4,5)P3 is required for Syntaxin1A clustering and neurotransmitter release.

    Science.gov (United States)

    Khuong, Thang Manh; Habets, Ron L P; Kuenen, Sabine; Witkowska, Agata; Kasprowicz, Jaroslaw; Swerts, Jef; Jahn, Reinhard; van den Bogaart, Geert; Verstreken, Patrik

    2013-03-20

    PI(3,4,5)P3 is a low-abundance lipid thought to play a role in the regulation of synaptic activity; however, the mechanism remains obscure. We have constructed novel split Venus-based probes and used superresolution imaging to localize PI(3,4,5)P3 at Drosophila larval neuromuscular synapses. We find the lipid in membrane domains at neurotransmitter release sites, where it concentrates with Syntaxin1A, a protein essential for vesicle fusion. Reducing PI(3,4,5)P3 availability disperses Syntaxin1A clusters and increasing PI(3,4,5)P3 levels rescues this defect. In artificial giant unilamellar vesicles, PI(3,4,5)P3 also induces Syntaxin1A domain formation and this clustering, in vitro and in vivo, is dependent on positively charged residues in the Syntaxin1A-juxtamembrane domain. Functionally, reduced PI(3,4,5)P3 causes temperature-sensitive paralysis and reduced neurotransmitter release, a phenotype also seen in animals expressing a Syntaxin1A with a mutated juxtamembrane domain. Thus, our data indicate that PI(3,4,5)P3, based on electrostatic interactions, clusters Syntaxin1A at release sites to regulate neurotransmitter release.

  1. PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site.

    Science.gov (United States)

    Bothe, Ingo; Deng, Su; Baylies, Mary

    2014-06-01

    Cell-cell fusion is a regulated process that requires merging of the opposing membranes and underlying cytoskeletons. However, the integration between membrane and cytoskeleton signaling during fusion is not known. Using Drosophila, we demonstrate that the membrane phosphoinositide PI(4,5)P2 is a crucial regulator of F-actin dynamics during myoblast fusion. PI(4,5)P2 is locally enriched and colocalizes spatially and temporally with the F-actin focus that defines the fusion site. PI(4,5)P2 enrichment depends on receptor engagement but is upstream or parallel to actin remodeling. Regulators of actin branching via Arp2/3 colocalize with PI(4,5)P2 in vivo and bind PI(4,5)P2 in vitro. Manipulation of PI(4,5)P2 availability leads to impaired fusion, with a reduction in the F-actin focus size and altered focus morphology. Mechanistically, the changes in the actin focus are due to a failure in the enrichment of actin regulators at the fusion site. Moreover, improper localization of these regulators hinders expansion of the fusion interface. Thus, PI(4,5)P2 enrichment at the fusion site encodes spatial and temporal information that regulates fusion progression through the localization of activators of actin polymerization.

  2. PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin-actin interactions.

    Science.gov (United States)

    Hong, Nan Hyung; Qi, Aidong; Weaver, Alissa M

    2015-08-31

    Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7(+) endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor-induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover.

  3. Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD.

    Science.gov (United States)

    Kim, Hyoji; Choi, Hoyun; Lee, Suk Kyeong

    2015-01-28

    Although Epstein-Barr virus (EBV) BamHI A rightward transcript (BART) microRNAs (miRNAs) are ubiquitously expressed in EBV-associated tumors, the role of most BART miRNAs is unclear. In this study, we showed that Bcl-2-associated death promoter (BAD) expression was significantly lower in EBV-infected AGS-EBV cells than in EBV-negative AGS cells and investigated whether BART miRNAs target BAD. Using bioinformatics analysis, five BART miRNAs showing seed match with the 3' untranslated region (3'-UTR) of BAD were selected. Of these, only miR-BART20-5p reduced BAD expression when individually transfected into AGS cells. A luciferase assay revealed that miR-BART20-5p directly targets BAD. The expression of BAD mRNA and protein was decreased by miR-BART20-5p and increased by an inhibitor of miR-BART20-5p. PE-Annexin V staining and cell proliferation assays showed that miR-BART20-5p reduced apoptosis and enhanced cell growth. Furthermore, miR-BART20-5p increased chemoresistance to 5-fluorouracil and docetaxel. Our data suggest that miR-BART20-5p contributes to tumorigenesis of EBV-associated gastric carcinoma by directly targeting the 3'-UTR of BAD.

  4. Research on Strategies for the Government to Deal With Online Public Opinion in We-Media Era%自媒体时代政府应对网络舆情策略研究

    Institute of Scientific and Technical Information of China (English)

    郭三强; 陈静; 王燕华; 胡晖

    2015-01-01

    The production of We-Media makes the network public opinions evolve rapidly,making the gov-ernment face new challenges.Based on summarizing the characteristics of network public opinion in the age of We-Media,the paper analyzes the problems and reasons when dealing with network public opinion,and proposes the corresponding strategies.%自媒体的产生使网络舆情发展迅猛,政府应对出现了新挑战.本文在概括自媒体时代网络舆情特点的基础上,分析了政府应对网络舆情存在的问题及原因,并提出了政府应对策略.

  5. Governing Warfare

    DEFF Research Database (Denmark)

    Harste, Gorm

      It would seem as though warfare has gotten out of control, not only in Iraq and Afghanistan, but also in Central Africa. The paper outlines the strategic history of politically controlled warfare since the early Enlightenment. The argument is that control is implausible. The idea of control has...... the risks of lacking unity and displays the organisational trap to the fatal political myth of controlled warfare: Does it come from the military organisation system itself, from political ideologies of goal-rational governance, or from the chameleonic logic of wars?  ...... administration. While organisation systems continue to make some kind of political control possible, this is not the case in relation to wars. The organisation system is the in-between that should mediatise politics and war but is not functionally equivalent to just and unjust wars. The paper investigates...

  6. Internet Governance

    Directory of Open Access Journals (Sweden)

    Pedro Veiga

    2010-01-01

    Full Text Available It has now become quite obvious that the Internet has brought significant changes to our society and a break on how we lived before its emergence. It is still too early to assess the impact on society of the new services at our disposal, such as the capacity to communicate faster and cheaper on a global scale, access information and, perhaps more importantly, to produce and disseminate information in a way that is accessible to all.It is clear that the advent of the Information Society implies changes in our society that constitute a point of no return. However, contrary to what happened when we entered the Industrial Age about three centuries ago, when the changing process was slow and led by older individuals, these days the entrance into the Information Society is taking place rapidly and the decisive players are younger people. The global nature of the Internet, the possibility of producing and distributing any type of content in digital form at almost zero cost, as well as the vast number of people who use the web, have highlighted the need for new forms of intervention in a sector where there are many types of players. It is in this context that the problem of Internet Governance becomes a very current issue, inasmuch as one feels the need to guarantee a diversity of rights and duties, which may appear difficult to reconcile.This paper presents a brief overview of the main players and initiatives which, in the field of Internet Governance, have tried to contribute to turning this network into a factor for social development and democraticity on a global scale.

  7. Urban Governance of Disease

    Directory of Open Access Journals (Sweden)

    Julie E. Fischer

    2012-04-01

    Full Text Available Rapid population growth, urbanization, and the growing challenges faced by the urban poor require redefining the paradigm for public health interventions in the 21st century, creating new approaches that take urban determinants of health into consideration. The widening disparity between the urban poor and the urban rich further exacerbates health inequities. Existing tools for global governance of urban health risks fall short, particularly in the lack of formal mechanisms to strengthen collaboration and communication among national and municipal agencies and between their local and international non-governmental partners. There is also a clear disconnect between governance strategies crafted at the international level and implementation on the ground. The challenge is to find common ground for global goods and municipal needs, and to craft innovative and dynamic policy solutions that can benefit some of the poorest citizens of the global urban network.

  8. Homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system at ER-PM junctions.

    Science.gov (United States)

    Chang, Chi-Lun; Liou, Jen

    2016-08-01

    The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca(2+) signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca(2+) from the endoplasmic reticulum (ER) store to the cytosol to activate Ca(2+)-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca(2+) must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca(2+). Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca(2+) influx across the PM is required to refill the ER Ca(2+) store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca(2+) signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca(2+) signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occur, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca(2+) signaling, including the ER Ca(2+) sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  9. Dawn of e-government

    DEFF Research Database (Denmark)

    Henriksen, Helle Zinner; Damsgaard, Jan

    2007-01-01

    Danish initiative implemented to stimulate e-government adoption. The e-Day initiative simply yet powerfully states that 'one governmental authority has the right to demand that its communication with another authority must be in electronic format' which is expected to create ripple effects both...... internally and externally. The e-Day initiative represents a drastic change in the former policy statements concerning IT adoption and diffusion in Danish government. The policy statements had previously been based on voluntary adoption focusing on visions and pedagogical intervention in governmental......Most countries have defined strategies for e-government. The objectives for implementing e-government are often defined but the means for fuelling the adoption and diffusion of e-government are typically less well clear in the policy statements. The present study assesses the impact of latest...

  10. Governance processes and change within organizational participants of multi-sectoral community health care alliances: the mediating role of vision, mission, strategy agreement and perceived alliance value.

    Science.gov (United States)

    Hearld, Larry R; Alexander, Jeffrey A

    2014-03-01

    Multi-sectoral community health care alliances are organizations that bring together individuals and organizations from different industry sectors to work collaboratively on improving the health and health care in local communities. Long-term success and sustainability of alliances are dependent on their ability to galvanize participants to take action within their 'home' organizations and institutionalize the vision, goals, and programs within participating organizations and the broader community. The purpose of this study was to investigate two mechanisms by which alliance leadership and management processes may promote such changes within organizations participating in alliances. The findings of the study suggest that, despite modest levels of change undertaken by participating organizations, more positive perceptions of alliance leadership, decision making, and conflict management were associated with a greater likelihood of participating organizations making changes as a result of their participation in the alliance, in part by promoting greater vision, mission, and strategy agreement and higher levels of perceived value. Leadership processes had a stronger relationship with change within participating organizations than decision-making style and conflict management processes. Open-ended responses by participants indicated that participating organizations most often incorporated new measures or goals into their existing portfolio of strategic plans and activities in response to alliance participation.

  11. Problems and strategies of cateringfood safety governance%餐饮业食品安全治理存在的问题及策略

    Institute of Scientific and Technical Information of China (English)

    韩秀婷

    2015-01-01

    Objective In order to improve food safety in catering food system to ensure people's physical and mental health, and strengthen the management of cateringfood safety. Methods The current status and problems existing in the cateringfoodsystemwereunderstood by means of investigation and interviews. Results Five problems exist in catering foodindustry security governance, including:characteristics of restaurant industry, complex causes of restaurant industry food safety, imperfection of food safety testing, and inspection system, more subject of restaurant industry food safety supervision and weak management of restaurant industry food safety. Four countermeasures wereput forward to, which including strengtheningself-disciplinein food safety industry itself, forming the supervision model of cooperation, improving the food safety inspection system and intensifying catering foodindustry illegal molecular composition.Conclusion The five questions andfour countermeasures are helpfulto the catering industry for the management of food safety problems.%目的:提高餐饮业食品安全,保障人们的身心健康,加强餐饮业食品安全的治理。方法通过调研、走访了解目前餐饮业食品安全现状及存在的问题。结果餐饮业食品安全治理存在的五个方面的问题,餐饮业自身特点、餐饮业食品安全成因复杂、食品安全检测检验体系不完善、餐饮业食品安全监管多主体、餐饮业食品安全自身管理薄弱。并提出了四个对策建议,增强餐饮业自身食品安全的自律,形成通力合作的监管模式,完善食品安全的检测检验体系,加大餐饮业违法分子的惩罚力度。结论总结出的五大问题和四大对策有利于餐饮业食品安全问题的治理。

  12. The Problem of Corporate Environmental Responsibility and Its Governance Strategy%中国企业社会环保责任困境与治理策略

    Institute of Scientific and Technical Information of China (English)

    叶陈毅; 罗书章; 陈爱英

    2016-01-01

    随着全球经济的飞速发展与人类物质水平的日益提高,环境污染危机已严重影响到人们的生活质量,公众对外部环境提出了更高的要求。以企业社会责任为出发点,强调环境保护责任,针对企业在生产发展过程中出现的高污染的难题,透析企业环保责任的滞后成因,通过实施环境战略管理和技术革新来提高生产力,减少对环境的污染,增强民众的环保意识,提高消费观念,提出关于企业自身、政府和消费者等方面的应对措施,以创立和改进企业环保责任治理体系,从而构建和谐社会,实现企业的可持续发展。%With the rapid development of economy, people's material living standards continue to improve, but the environmental pollution and damage has seriously affected people's lives, people's demands for the surrounding envi-ronment is getting higher and higher. The corporate social responsibility as the starting point, this article leads to corporate environmental protection responsibility, from the industry of high pollution of for textile companies in the process of production and development of high pollution present situation and confusion, analysis of lag reasons for corporate environmental responsibility, through the implementation of the environment of strategic management and technological innovation to improve productivity, reduce pollution to the environment, enhance the public's aware-ness of environmental protection, increase consumption ideas, also put forward the relevant countermeasures to deal with the enterprises themselves, the government and consumers, to build and improve the evaluation system of cor-porate environmental responsibility, so as to realize the enterprise sustainable development, building a harmonious society.

  13. PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels.

    Science.gov (United States)

    Itsuki, Kyohei; Imai, Yuko; Hase, Hideharu; Okamura, Yasushi; Inoue, Ryuji; Mori, Masayuki X

    2014-02-01

    Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7 are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2 depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and TRPC7 activity independently of DAG; however, the physiological role of PI(4,5)P2 reduction on channel activity remains unclear. We used Förster resonance energy transfer (FRET) to measure PI(4,5)P2 or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist stimulation of receptors that couple to Gq and thereby activate PLC. Measurements made at different levels of receptor activation revealed a correlation between the kinetics of PI(4,5)P2 reduction and those of receptor-operated TRPC6 and TRPC7 current activation and inactivation. In contrast, DAG production correlated with channel activation but not inactivation; moreover, the time course of channel inactivation was unchanged in protein kinase C-insensitive mutants. These results suggest that inactivation of receptor-operated TRPC currents is primarily mediated by the dissociation of PI(4,5)P2. We determined the functional dissociation constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used this constant to fit our experimental data to a model in which channel gating is controlled by PI(4,5)P2 and DAG. This model predicted similar FRET dynamics of the PHd to measured FRET in either human embryonic kidney cells or smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation failed to reproduce the experimental data, confirming the inhibitory role of PI(4,5)P2 depletion on TRPC currents. Our model also explains various PLC-dependent characteristics of channel activity, including limitation of maximum open probability, shortening of the peak time, and the bell-shaped response of total

  14. Binding of PLCδ1PH-GFP to Ptdlns(4,5)P2 prevents inhibition of phospholipase C-mediated hydrolysis of Ptdlns(4,5)P2 by neomycin

    Institute of Scientific and Technical Information of China (English)

    Chuan WANG; Xiao-na DU; Qing-zhong JIA; Hai-lin ZHANG

    2005-01-01

    Aim: To investigate the effects of the pleckstrin homology (PH) domain of phospholipase Cδ1 (PLCδ1PH) on inhibition of phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] by neomycin.Methods: A fusion construct of green fluorescent protein (GFP) and PLCδ1PH (PLCδ1PH-GFP), which is known to bind Ptdlns(4,5)P2 specifically, together with laser-scanning confocal microscopy, was used to trace PtdIns(4,5)P2 translocation.Results: Stimulation of the type 1 muscarinic receptor and the bradykinin 2 receptor induced a reversible PLCδ1PH-GFP translocation from the membrane to the cytosol in COS-7 cells. PLC inhibitor U73122 blocked the translocation.Wortmannin, a known PtdIns kinase inhibitor, did not affect the translocation induced by ACh, but blocked recovery after translocation, indicating that PtdIns(4,5)P2 hydrolysis occurs through receptor-mediated PLC activation.Neomycin, a commonly used phospholipase C blocker, failed to block the receptor-induced PLCδ1PH-GFP translocation, indicating that neomycin is unable to block PLC-mediated PtdIns(4,5)P2 hydrolysis. However, in the absence of PLCδ1PH-GFP expression, neomycin abolished the receptor-induced hydrolysis of PtdIns(4,5)P2 by PLC. Conclusion: Although PLCδ1PH and neomycin bind to PtdIns(4,5)P2 in a similar way, they have distinct effects on receptor-mediated activation of PLC and PtdIns(4,5)P2 hydrolysis.

  15. REGULATION OF HISTAMINE-INDUCED AND UTP-INDUCED INCREASES IN INS(1,4,5)P-3, INS(1,3,4,5)P-4 AND CA2+ BY CYCLIC-AMP IN DDT1 MF-2 CELLS

    NARCIS (Netherlands)

    SIPMA, H; DUIN, M; HOITING, B; DENHERTOG, A; NELEMANS, A

    1995-01-01

    1 Stimulation of P-2U-purinoceptors with UTP or histamine H-1-receptors with histamine gave rise to the formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P-4) in DDT1 MF-2 smooth muscle cells. 2 Stimulation of P-2U-purinoceptors or histamin

  16. National Privacy Research Strategy

    Data.gov (United States)

    Networking and Information Technology Research and Development, Executive Office of the President — On July 1, NITRD released the National Privacy Research Strategy. Research agencies across government participated in the development of the strategy, reviewing...

  17. On the causes of juvenile delinquency and governance strategy%浅谈农村青少年犯罪成因及治理策略

    Institute of Scientific and Technical Information of China (English)

    李峰

    2013-01-01

    The reform and opening up, with the rural economic policies, the introduction of new, rural productivity has been greatly liberated, resulting in a large number of surplus labor, they poured into the city and region, seek the new way of life, because the comparison of difference of the rich and the poor living conditions, low, stimulate some adolescents in rural areas have a strong material desire, but because the legitimate means, the desire of the ability, lack of conditions, resulting in a part of people rush into danger, cause of crime, juvenile crime in rural areas in recent years, the upward trend, therefore causes of rural juvenile crime and the control strategy has the important practical significance.%  改革开放后,随着新的农村经济政策的出台,农村的生产力得到了极大的解放,造成大量的剩余劳动力,他们涌入城市和发达地区,寻求新的生活方式,由于贫富差别的对比,生活条件的低下,刺激了一些农村青少年产生了强烈的物质欲望,但是由于欲望的正当手段、能力、条件的欠缺,致使一部份人铤而走险,导致犯罪,近些年来农村青少年犯罪呈上升的趋势,为此探讨农村青少年犯罪成因及治理策略具有重要的现实意义。

  18. Quantitative analysis of photoquadrats 1-35 acquired at Baker Island permanent transect site 5P on March 19, 2000

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This spreadsheet summarizes the number of corals photographed along a permanent transect line at Underwater Site 5P at Baker Island on 3/19/2000.

  19. Quantitative analysis of photoquadrats acquired at Howland Island permanent transect site 5P on January 21, 2004

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This spreadsheet summarizes the number of corals photographed along a permanent transect line at Underwater Site 5P at Howland Island on 1/21/2004.

  20. Quantitative analysis of photoquadrats acquired at Johnston Atoll permanent transect site 5P on July 2, 2000

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This spreadsheet summarizes the number of corals photographed along a permanent transect line at Underwater Site 5P at Johnston Atoll on 7/2/2000.

  1. Quantitative analysis of photoquadrats acquired at Kingman Reef permanent transect site 5P on March 17, 2002

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This spreadsheet summarizes the number of corals photographed along a permanent transect line at Underwater Site 5P at Kingman Reef on 3/17/2002.

  2. A combined M5P tree and hazard-based duration model for predicting urban freeway traffic accident durations.

    Science.gov (United States)

    Lin, Lei; Wang, Qian; Sadek, Adel W

    2016-06-01

    The duration of freeway traffic accidents duration is an important factor, which affects traffic congestion, environmental pollution, and secondary accidents. Among previous studies, the M5P algorithm has been shown to be an effective tool for predicting incident duration. M5P builds a tree-based model, like the traditional classification and regression tree (CART) method, but with multiple linear regression models as its leaves. The problem with M5P for accident duration prediction, however, is that whereas linear regression assumes that the conditional distribution of accident durations is normally distributed, the distribution for a "time-to-an-event" is almost certainly nonsymmetrical. A hazard-based duration model (HBDM) is a better choice for this kind of a "time-to-event" modeling scenario, and given this, HBDMs have been previously applied to analyze and predict traffic accidents duration. Previous research, however, has not yet applied HBDMs for accident duration prediction, in association with clustering or classification of the dataset to minimize data heterogeneity. The current paper proposes a novel approach for accident duration prediction, which improves on the original M5P tree algorithm through the construction of a M5P-HBDM model, in which the leaves of the M5P tree model are HBDMs instead of linear regression models. Such a model offers the advantage of minimizing data heterogeneity through dataset classification, and avoids the need for the incorrect assumption of normality for traffic accident durations. The proposed model was then tested on two freeway accident datasets. For each dataset, the first 500 records were used to train the following three models: (1) an M5P tree; (2) a HBDM; and (3) the proposed M5P-HBDM, and the remainder of data were used for testing. The results show that the proposed M5P-HBDM managed to identify more significant and meaningful variables than either M5P or HBDMs. Moreover, the M5P-HBDM had the lowest overall mean

  3. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China); Wei, Guangkuan [Department of Neurology, Heilongjiang Provincial Hospital, Harbin 150036 (China); Di, Zhiyong [Department of Laboratory, Heilongjiang Provincial Hospital, Harbin 150036 (China); Zhao, Qingjie, E-mail: zhaoqingjie2013@163.com [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China)

    2014-09-26

    Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

  4. Active vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency.

    Science.gov (United States)

    Compton, Lauren M; Ikonomov, Ognian C; Sbrissa, Diego; Garg, Puneet; Shisheva, Assia

    2016-09-01

    The two evolutionarily conserved mammalian lipid kinases Vps34 and PIKfyve are involved in an important physiological relationship, whereby the former produces phosphatidylinositol (PtdIns) 3P that is used as a substrate for PtdIns(3,5)P2 synthesis by the latter. Reduced production of PtdIns(3,5)P2 in proliferating mammalian cells is phenotypically manifested by the formation of multiple translucent cytoplasmic vacuoles, readily rescued upon exogenous delivery of PtdIns(3,5)P2 or overproduction of PIKfyve. Although the aberrant vacuolation phenomenon has been frequently used as a sensitive functional measure of localized PtdIns(3,5)P2 reduction, cellular factors governing the appearance of cytoplasmic vacuoles under PtdIns3P-PtdIns(3,5)P2 loss remain elusive. To gain further mechanistic insight about the vacuolation process following PtdIns(3,5)P2 reduction, in this study we sought for cellular mechanisms required for manifestation of the aberrant endomembrane vacuoles triggered by PIKfyve or Vps34 dysfunction. The latter was achieved by various means such as pharmacological inhibition, gene disruption, or dominant-interference in several proliferating mammalian cell types. We report here that inhibition of V-ATPase with bafilomycin A1 as well as inactivation of the GTP-GDP cycle of Rab5a GTPase phenotypically rescued or completely precluded the cytoplasmic vacuolization despite the continued presence of inactivated PIKfyve or Vps34. Bafilomycin A1 also restored the aberrant EEA1-positive endosomes, enlarged upon short PIKfyve inhibition with YM201636. Together, our work identifies for the first time that factors such as active V-ATPase or functional Rab5a cycle are acting coincidentally with the PtdIns(3,5)P2 reduction in triggering formation of aberrant cytoplasmic vacuoles under PIKfyve or Vps34 dysfunction.

  5. Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae.

    Science.gov (United States)

    Rogers, Jason V; Rose, Mark D

    2014-12-02

    During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p's functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion.

  6. miR-483-5p and miR-486-5p are down-regulated in cumulus cells of metaphase II oocytes from women with polycystic ovary syndrome.

    Science.gov (United States)

    Shi, Lin; Liu, Shan; Zhao, Wanqiu; Shi, Juanzi

    2015-10-01

    The aim of this study was to compare the expression of microRNAs (miRNAs) in cumulus cells from polycystic ovary syndrome (PCOS) and non-PCOS women. In the present study, miRNA expression profiles of the cumulus cell samples were determined by miRNA microarrays. Quantification of selected miRNAs and predicted target genes was performed using quantitative real-time PCR (qRT-PCR). The results showed that miR-483-5p and miR-486-5p are significantly decreased in cumulus cells of PCOS patients PCOS (fold change >2, false discovery rate <0.001). qRT-PCR found that four predicted genes, SOCS3, SRF, PTEN and FOXO1, were significantly increased in PCOS cumulus cells (all P < 0.001), and IGF2 (host gene of miR-483-5p) was significantly decreased in PCOS cumulus cells (P < 0.001). These results indicated that miR-483-5p might play an important role in reducing insulin resistance, and that miR-486-5p might promote cumulus cell proliferation through activation of PI3K/Akt. The findings from this study provided new insights into the complex molecular mechanisms involved in PCOS by revealing pathways possibly regulated by miRNAs. The differences in miRNAs (miR-483-5p, miR-486-5p) and their target gene expression in cumulus cells may provide clues for future research and help to explain aberrant follicular development and subfertility in women with PCOS.

  7. A Structural Equation Model (SEM of Governing Factors Influencing the Implementation of T-Government

    Directory of Open Access Journals (Sweden)

    Sameer Alshetewi

    2015-11-01

    Full Text Available Governments around the world have invested significant sums of money on Information and Communication Technology (ICT to improve the efficiency and effectiveness of services been provided to their citizens. However, they have not achieved the desired results because of the lack of interoperability between different government entities. Therefore, many governments have started shifting away from the original concept of e-Government towards a much more transformational approach that encompasses the entire relationship between different government departments and users of public services, which can be termed as transformational government (t- Government. In this paper, a model is proposed for governing factors that impact the implementation of t-Government such as strategy, leadership, stakeholders, citizen centricity and funding in the context of Saudi Arabia. Five constructs are hypothesised to be related to the implementation of t-Government. To clarify the relationships among these constructs, a structural equation model (SEM is utilised to examine the model fit with the five hypotheses. The results show that there are positive and significant relationships among the constructs such as the relationships between strategy and t-Government; the relationships between stakeholders and t-Government; the relationships between leadership and t-Government. This study also showed an insignificant relationship between citizens’ centricity and t-Government and also an insignificant relationship between funding and t-Government. document is a “live” template and already defines the components of your paper [title, text, heads, etc.] in its style sheet.

  8. Building Blocks of an E-Government: A Framework

    OpenAIRE

    Sharma, Sushil K.; Jatinder N. Gupta

    2003-01-01

    The movement toward electronic government (e-government) is rapidly advancing as nations exploit new electronic means of communication such as the Internet. The e-government transformation process can be and often is seriously hindered when initiatives are disjointed and uncoordinated by an overall strategy. Although many countries are creating e-government services, there is no documentation of an e-government framework to guide the process. Guidelines for implementation of e-government are ...

  9. miR-382-5p Controls Hematopoietic Stem Cell Differentiation Through the Downregulation of MXD1.

    Science.gov (United States)

    Zini, Roberta; Rossi, Chiara; Norfo, Ruggiero; Pennucci, Valentina; Barbieri, Greta; Ruberti, Samantha; Rontauroli, Sebastiano; Salati, Simona; Bianchi, Elisa; Manfredini, Rossella

    2016-10-01

    microRNAs are key regulators of gene expression that control stem cell fate by posttranscriptional downregulation of hundreds of target genes through seed pairing in their 3' untranslated region. In fact, miRNAs tightly regulate fundamental stem cell processes, like self-renewal, proliferation, and differentiation; therefore, miRNA deregulation may contribute to the development of solid tumors and hematological malignancies. miR-382-5p has been found to be upregulated in patients with myeloid neoplasms, but its role in normal hematopoiesis is still unknown. In this study, we demonstrated that miR-382-5p overexpression in CD34(+) hematopoietic stem/progenitor cells (HSPCs) leads to a significant decrease of megakaryocyte precursors coupled to increase of granulocyte ones. Furthermore, by means of a computational analysis using different prediction algorithms, we identified several putative mRNA targets of miR-382-5p that are downregulated upon miRNA overexpression (ie, FLI1, GATA2, MAF, MXD1, RUNX1, and SGK1). Among these, we validated MXD1 as real target of miR-382-5p by luciferase reporter assay. Finally, we showed that MXD1 knockdown mimics the effects of miR-382-5p overexpression on granulocyte and megakaryocyte differentiation of CD34(+) cells. Overall, our results demonstrated that miR-382-5p expression favors the expansion of granulocyte lineage and impairs megakaryocyte commitment through MXD1 downregulation. Therefore, our data showed for the first time that the miR-382-5p/MXD1 axis plays a critical role in myelopoiesis by affecting the lineage choice of CD34(+) HSPCs.

  10. Role of miR-181a-5p and endoplasmic reticulum stress in the regulation of myogenic differentiation.

    Science.gov (United States)

    Wei, Yingying; Tao, Xuelian; Xu, Huaming; Chen, Yan; Zhu, Li; Tang, Guoqing; Li, Mingzhou; Jiang, Anan; Shuai, Surong; Ma, Jideng; Jin, Long; Wen, Anxiang; Wang, Qin; Zhu, Guangxiang; Xie, Meng; Wu, Jiayun; He, Tao; Jiang, Yanzhi; Li, Xuewei

    2016-10-30

    Accumulating evidence has indicated that microRNAs (miRNAs) and endoplasmic reticulum (ER) stress play critical roles in myoblast differentiation. However, the regulation roles of miRNAs and ER stress in myogenic differentiation have not been fully revealed and need to be further studied. Here, we discovered that the expression levels of miR-181a-5p were strongly upregulated during C2C12 cell differentiation. miR-181a-5p overexpression promoted ER stress and differentiation of C2C12 cells, which was accompanied by increasing expression levels of marker genes related to ER stress-mediated apoptosis and myogenic differentiation. Opposite results were observed after inhibition of the miR-181a-5p expression. The gain- and loss-of-function experiments on C2C12 cells showed that miR-181a-5p affected the development of muscle fiber type, but had no significant influence on C2C12 cell proliferation. In the ER-stressed C2C12 cells induced by thapsigargin (Tg), the expression levels of both miR-181a-5p and marker genes related to ER stress and myogenesis were upregulated. In the ER-stressed C2C12 cells and porcine muscle fibroblast (PMF) cells pretreated with Tg, we found that miR-181a-5p targeted glucose-regulated protein, 78kDa/binding immunoglobulin protein (GRP78/BIP), and influenced cell apoptosis. In conclusion, these results indicate that miR-181a-5p and ER stress have positive synergistic effects on myogenic differentiation by increasing the expression levels of myogenic differentiation key genes and activating the ER stress-mediated apoptosis signaling pathway.

  11. Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

    Directory of Open Access Journals (Sweden)

    Chao-Yu Pan

    2017-01-01

    Full Text Available MicroRNAs (miRNAs play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

  12. IT governance a pocket guide

    CERN Document Server

    Calder, Alan

    2007-01-01

    This new downloadable pocket guide in the Practical IT Governance series, is designed to provide the reader with a basic understanding of how an organization's Information Technology supports and enables the achievement of its strategies and objectives.

  13. 我国服务外包产业集群的治理策略研究%Study on the Governance Strategy of Service Outsourcing Clusters in China

    Institute of Scientific and Technical Information of China (English)

    陈建斌; 付丽丽; 牛敏杰

    2014-01-01

    With the rapid development of outsourcing clusters, we need more effective and accurate industrial policy. Industrial cluster is a kind of organization with rich social capital and the demand of clusters surplus is one of the motivations of industry centralization. This paper firstly teased out the current situation of effect evaluation of service outsourcing policies and proposed the core thinking that policies should be made and evaluated in view of cluster governance. Secondly, the social capital characteristic of cluster surplus of cluster governance and the dominant position of our government had been studied, then it constructed a structure entropy model of industrial cluster network in order to exhibit the evolution of social capital or cluster surplus in it and discussed the governance strategy of industrial clusters. In the end, it is proposed that the industrial policies should be revised from decreasing operation cost to advancing social capital or cluster surplus. With such strategies as providing more public service or products, developing informal relationship and building transaction platform, the cluster network should be stickier and more good factors of production should be collected so as to improve the vitality and competiveness of industrial cluster.%服务外包产业集群快速发展,需要更有效、更准确的产业政策继续扶持。产业集群是社会资本丰富的组织,集群剩余索取权是产业集聚的动力之一。文章对服务外包产业政策效果评价现状进行了梳理,提出了从产业集群治理层面进行政策制定及效果评估的核心思想,并进一步分析了产业集群治理的基本机制-集群剩余索取权的社会资本特性以及政府在产业集群治理中主导作用的形成,建构了产业集群网络的结构熵模型以反映社会资本或集群剩余的演化。有关基于熵变的产业集群治理策略方面,文章提出产业政策应从降低企业经营成

  14. 韩国政府反腐倡廉策略及其对我国的启示%The Implementation of Anti-corruption Strategies by Korea's Government and the Significance to China

    Institute of Scientific and Technical Information of China (English)

    许吉

    2012-01-01

    韩国曾经是一个腐败问题比较严重的国家之一。为打击腐败和发展经济,韩国走过了一条曲折的反腐败道路,并经过多年的努力正在逐步走向清廉的国家。综观其反腐历程,韩国政府所采取的行政伦理法制化策略、政府运作"阳光机制"策略、加大腐败成本策略、鼓励社会力量参与反腐败策略等,对有效遏制与消除公职人员和公共部门的腐败起到了十分重要的作用,确实有不少经验值得中国借鉴。%Korea has made great efforts to fight against corruption and develop its economy, and now a clean and honest government is being built. The successful implementation of anti-corruption strategies in- cluding the legalization of administrative ethics, the "sunshine mechanism" of government operation, the increase of corruption cost and the participation of nongovernmental sectors in anti-corruption plays impor- tant role in restraining and eliminating corruption by civil servants and public sectors. All this is beneficial to China to refer to in fighting against its corruption.

  15. Ins(1,4,5)P3 receptor-mediated Ca2+ signaling and autophagy induction are interrelated.

    Science.gov (United States)

    Decuypere, Jean-Paul; Welkenhuyzen, Kirsten; Luyten, Tomas; Ponsaerts, Raf; Dewaele, Michael; Molgó, Jordi; Agostinis, Patrizia; Missiaen, Ludwig; De Smedt, Humbert; Parys, Jan B; Bultynck, Geert

    2011-12-01

    The role of intracellular Ca2+ signaling in starvation-induced autophagy remains unclear. Here, we examined Ca2+ dynamics during starvation-induced autophagy and the underlying molecular mechanisms. Tightly correlating with autophagy stimulation, we observed a remodeling of the Ca2+ signalosome. First, short periods of starvation (1 to 3 h) caused a prominent increase of the ER Ca2+-store content and enhanced agonist-induced Ca2+ release. The mechanism involved the upregulation of intralumenal ER Ca2+-binding proteins, calreticulin and Grp78/BiP, which increased the ER Ca2+-buffering capacity and reduced the ER Ca2+ leak. Second, starvation led to Ins(1,4,5)P3R sensitization. Immunoprecipitation experiments showed that during starvation Beclin 1, released from Bcl-2, first bound with increasing efficiency to Ins(1,4,5)P3Rs; after reaching a maximal binding after 3 h, binding, however, decreased again. The interaction site of Beclin 1 was determined to be present in the N-terminal Ins(1,4,5)P3-binding domain of the Ins(1,4,5)P3R. The starvation-induced Ins(1,4,5)P3R sensitization was abolished in cells treated with BECN1 siRNA, but not with ATG5 siRNA, pointing toward an essential role of Beclin 1 in this process. Moreover, recombinant Beclin 1 sensitized Ins(1,4,5)P3Rs in 45Ca2+-flux assays, indicating a direct regulation of Ins(1,4,5)P3R activity by Beclin 1. Finally, we found that Ins(1,4,5)P3R-mediated Ca2+ signaling was critical for starvation-induced autophagy stimulation, since the Ca2+ chelator BAPTA-AM as well as the Ins(1,4,5)P3R inhibitor xestospongin B abolished the increase in LC3 lipidation and GFP-LC3-puncta formation. Hence, our results indicate a tight and essential interrelation between intracellular Ca2+ signaling and autophagy stimulation as a proximal event in response to starvation.

  16. Endomembrane PtdIns(3,4,5)P3 activates the PI3K-Akt pathway.

    Science.gov (United States)

    Jethwa, Nirmal; Chung, Gary H C; Lete, Marta G; Alonso, Alicia; Byrne, Richard D; Calleja, Véronique; Larijani, Banafshé

    2015-09-15

    PKB/Akt activation is a common step in tumour growth, proliferation and survival. Akt activation is understood to occur at the plasma membrane of cells in response to growth factor stimulation and local production of the phosphoinositide lipid phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] following phosphoinositide 3-kinase (PI3K) activation. The metabolism and turnover of phosphoinositides is complex--they act as signalling molecules as well as structural components of biological membranes. The localisation and significance of internal pools of PtdIns(3,4,5)P3 has long been speculated upon. By using transfected and recombinant protein probes for PtdIns(3,4,5)P3, we show that PtdIns(3,4,5)P3 is enriched in the nuclear envelope and early endosomes. By exploiting an inducible dimerisation device to recruit Akt to these compartments, we demonstrate that Akt can be locally activated in a PtdIns(3,4,5)P3-dependent manner and has the potential to phosphorylate compartmentally localised downstream substrates. This could be an important mechanism to regulate Akt isoform substrate specificity or influence the timing and duration of PI3K pathway signalling. Defects in phosphoinositide metabolism and localisation are known to contribute to cancer, suggesting that interactions at subcellular compartments might be worthwhile targets for therapeutic intervention.

  17. Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

    Directory of Open Access Journals (Sweden)

    Alessandra Mangolini

    2014-01-01

    Full Text Available Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs, which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma.

  18. Involvement of microRNA-135a-5p in the Protective Effects of Hydrogen Sulfide Against Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Yuanyuan Liu

    2016-11-01

    Full Text Available Background/Aims: Development of effective therapeutic drugs for Parkinson's disease is in great need. During the progression of Parkinson's disease, Rho-associated protein kinase 2 (ROCK2 is activated to promote neurodegeneration. Hydrogen sulfide (H2S has a neuroprotective effect during the neural injury of Parkinson's disease. However, the mechanisms that underlie the effects of ROCK2 and H2S remain ill-defined. In the current study, we addressed these questions. Methods: We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced mouse subacute model of Parkinson's disease to study the effects of H2S on astrocytic activation in the mouse striatum, on the levels of tyrosine-hydroxylase (TH-positive neuron loss, on the apomorphine-induced rotational behavior of the mice, and on the changes in ROCK2 and miR-135a-5p expression. Plasmid transfection was applied to modify miR-135a-5p levels in a neuronal cell line HCN-1A. Bioinformatics analysis was performed to predict the relationship between ROCK2 and miR-135a-5p in neuronal cells, and then was confirmed by luciferase reporter assay. Results: H2S alleviated MPTP-induced astrocytic activation in the mouse striatum, alleviated the increases in TH-positive neuron loss, and improved the apomorphine-induced rotational behavior of the mice. H2S significantly attenuated the increases in ROCK2 and the decreases in miR-135a-5p by MPTP. MiR-135a-5p targeted the 3'-UTR of ROCK2 mRNA to inhibit its translation in neuronal cells. Conclusion: MiR-135a-5p-regulated ROCK2 may play a role in the protective effects of hydrogen sulfide against Parkinson's disease.

  19. Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.

    Science.gov (United States)

    Wong, Albert; Grubb, David R; Cooley, Nicola; Luo, Jieting; Woodcock, Elizabeth A

    2013-01-01

    Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic responses in neonatal rat ventricular myocytes (NRVM). Treatment with the IP(3)-receptor (IP(3)-R) antagonist 2-aminoethoxydiphenyl borate (2-APB) at 5 or 20 μmol/L resulted in an increase in autophagosome content, defined as puncta labeled by antibody to microtubule associated light chain 3 (LC3). 2-APB also increased autophagic flux, indicated by heightened LC3II accumulation, which was further enhanced by bafilomycin (10nmol/L). Expression of Ins(1,4,5)P(3) 5-phosphatase (IP(3)-5-Pase) to deplete Ins(1,4,5)P(3) also increased LC3-labeled puncta and LC3II content, suggesting that Ins(1,4,5)P(3) inhibits autophagy. The IP(3)-R can act as an inhibitory scaffold sequestering the autophagic effector, beclin-1 to its ligand binding domain (LBD). Expression of GFP-IP(3)-R-LBD inhibited autophagic signaling and furthermore, beclin-1 co-immunoprecipitated with the IP(3)-R-LBD. A mutant GFP-IP(3)-R-LBD with reduced ability to bind Ins(1,4,5)P(3) bound beclin-1 and inhibited autophagy similarly to the wild type sequence. These data provide evidence that Ins(1,4,5)P(3) and IP(3)-R act as inhibitors of autophagic responses in cardiomyocytes. By suppressing autophagy, IP(3)-R may contribute to cardiac pathology.

  20. MiR-129-5p-mediated Beclin-1 suppression inhibits endothelial cell autophagy in atherosclerosis.

    Science.gov (United States)

    Geng, Zhaohua; Xu, Fei; Zhang, Yiguan

    2016-01-01

    Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells antagonizes the development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-129-5p (miR-129-5p) is a well-defined tumor suppressorin some types of cancer, while it is unknown whether miR-129-5p may also play a role in the development of atherosclerosis. Here, we addressed this question in the current study. We examined the levels of endothelial cell autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of Beclin-1 and the levels of miR-129-5p in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-129-5p and 3'-UTR of Beclin-1 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-129-5p were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). We found that HFD mice developed atherosclerosisin 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as CTL mice) did not. Compared to CTL mice, HFD mice had significantly lower levels of endothelial cell autophagy, resulting from decreases in Beclin-1 protein, but not mRNA. The decreases in Beclin-1 in endothelial cells were due to HFD-induced increases inmiR-129-5p, which suppressed the translation of Beclin-1 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Together, these data suggest that upregulation of miR-129-5p by HFD may impair the protective effects of endothelial cell autophagy against development of atherosclerosis through suppressing protein translation of Beclin-1.

  1. SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

    DEFF Research Database (Denmark)

    Wainwright, Elanor N; Jorgensen, Joan S; Kim, Youngha;

    2013-01-01

    . Expression of the primary transcript of miR-202-5p/3p remained low in XY gonads in a conditional Sox9-null mouse model, suggesting that pri-miR-202 transcription is downstream of SOX9, a transcription factor that is both necessary and sufficient for male sex determination. We identified the pri-miR-202...... findings indicate that expression of the conserved gonad microRNA, miR-202-5p/3p, is downstream of the testis-determining factor SOX9, suggesting an early role in testis development....

  2. miR-181b-5p, miR-195-5p and miR-301a-3p are related with treatment resistance in schizophrenia.

    Science.gov (United States)

    Alacam, Huseyin; Akgun, Sakir; Akca, Hakan; Ozturk, Onder; Kabukcu, Burge Basay; Herken, Hasan

    2016-11-30

    The aim of the study was to determine the differences between expression levels of certain miRNAs, as their association with schizophrenia has been well presented in the literature, and to investigate their relation to treatment resistance in schizophrenic patients. Three groups were formed: 1) treatment-resistant group, 2) treatment responsive group and 3) healthy control group. Expression levels of miRNAs from peripheric blood samples were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We investigated the roles of 29 schizophrenia-related miRNAs in schizophrenia treatment and their potentials to be considered as indicators. Among these miRNAs, only miR-181b-5p, miR-195-5p and miR-301a-3p expressions were found to be significantly different between the treatment-resistant group and the group responding well to the treatment. miRNAs may cause resistance by silencing the receptor genes of the drugs used for schizophrenia treatment. miR-181b-5p, miR-195-5p and miR-301a-3p may be candidate indicators that can be used to reveal resistance against schizophrenia treatment.

  3. Governance Structure, Product Diversification, and Performance

    NARCIS (Netherlands)

    A.A.C.J. van Oijen; G.W.J. Hendrikse (George)

    2002-01-01

    textabstractProduct diversification and its financial outcomes have been studied exhaustively. However, previous literature has focused on corporations, ignoring other important legal organizations or governance structures. In this paper, we study the diversification strategies of cooperatives and c

  4. Sistemi documentari ed e-government

    OpenAIRE

    Giuva, Linda

    2006-01-01

    The text analyses the role of record management strategies in the e-government process. In this context information technology, policy, standard and procedures are essential to reach the integration between record management and content management.

  5. 论G20机制化及中国在全球经济治理中的策略%Institutionalization of G20 and China's Strategy in Global Economic Governance

    Institute of Scientific and Technical Information of China (English)

    邹亚宝; 王凯

    2011-01-01

    2008年金融危机以来,G20成为最重要的国际经济协商机制。本文对(320机制化的动因和制约因素加以分析,认为G20机制化的主要动因是金融危机后世界力量格局和经济结构的变迁。而由于G20受到内部和外部的双重制约,其机制化前景并不明朗,很难突破原有的G8模式。本文在此基础上提出中国在全球经济治理中的策略。%G20 has become the most important international economic consultation mechanism after the financial crisis in 2008. This article analyzes the motivations and constraints of the G20 institutionalization, and points out that the pivotal reason of its institutionalization is the change of the power pattern and the economic structure of the world after the financial crisis. Moreover, as the G20 is restricted by both the internal and external factors, its institutionalizing prospect is still uncertain. It may not be able to dismantle the basis of G8. With this consideration, the article offers some useful strategies for China in global economic governance.

  6. 基于空间格局的西安大都市主体功能区划管治策略%Zoning Governance Strategy of the Metropolitan Main Function of Xi’an Based on Spatial Pattern

    Institute of Scientific and Technical Information of China (English)

    刘冬; 王欣

    2014-01-01

    本文基于对西安大都市区的空间格局窘况,进一步审视主体功能区划作为协调各类空间规划和专项规划、提高资源利用效率的要义,立足于规划体制、资源环境承载力和城乡发展,提出西安大都市区主体功能区划的管治策略。%This paper based on the predicament of the spatial pat ern of Xi’an metropolitan area, further examines the es-sence of the main function division as the coordination of va-rious spatial planning and special planning, improvement the efficiency of resource use, based on the planning system, the bearing capacity of resources, environment and urban and rural development, puts forward the governance strategy of main function zoning of Xi'an metropolitan.

  7. Audit mode change, corporate governance

    Directory of Open Access Journals (Sweden)

    Limei Cao

    2015-12-01

    Full Text Available This study investigates changes in audit strategy in China following the introduction of risk-based auditing standards rather than an internal control-based audit mode. Specifically, we examine whether auditors are implementing the risk-based audit mode to evaluate corporate governance before distributing audit resources. The results show that under the internal control-based audit mode, the relationship between audit effort and corporate governance was weak. However, implementation of the risk-based mode required by the new auditing standards has significantly enhanced the relationship between audit effort and corporate governance. Since the change in audit mode, the Big Ten have demonstrated a significantly better grasp of governance risk and allocated their audit effort accordingly, relative to smaller firms. The empirical evidence indicates that auditors have adjusted their audit strategy to meet the regulations, risk-based auditing is being achieved to a degree, reasonable and effective corporate governance helps to optimize audit resource allocation, and smaller auditing firms in particular should urgently strengthen their risk-based auditing capability. Overall, our findings imply that the mandatory switch to risk-based auditing has optimized audit effort in China.

  8. Engineering governance: introducing a governance meta framework.

    NARCIS (Netherlands)

    Brand, N.; Beens, B.; Vuuregge, E.; Batenburg, R.

    2011-01-01

    There is a need for a framework that depicts strategic choices within an organisation with regard to potential governance structures. The governance meta framework provides the necessary structure in the current developments of governance. Performance as well as conformance are embedded in this fram

  9. MicroRNA-181b-5p, ETS1, and the c-Met pathway exacerbate the prognosis of pancreatic ductal adenocarcinoma after radiation therapy.

    Science.gov (United States)

    Tomihara, Hideo; Yamada, Daisaku; Eguchi, Hidetoshi; Iwagami, Yoshifumi; Noda, Takehiro; Asaoka, Tadafumi; Wada, Hiroshi; Kawamoto, Koichi; Gotoh, Kunihito; Takeda, Yutaka; Tanemura, Masahiro; Mori, Masaki; Doki, Yuichiro

    2017-03-01

    Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens show remnant tumor cells, which indicate that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the EMT and the presence of CSCs, were reported to be associated with resistance in various cancers. Previous reports showed that HGF could induce EMT in PDAC cells; moreover, the HGF receptor, c-Met, was identified as a dominant pancreatic CSC marker. However, the clinical significance of c-Met expression remains unclear. So, we hypothesized that remnant PDAC tissue after CRT might harbor cells with high c-Met expression, and these cells may exacerbate patients' prognosis. In the immunohistochemical analysis, we showed that preoperative CRT was significantly associated with high c-Met expression; moreover, high c-Met expression was a significant marker of a dismal prognosis. Next, we investigated mechanisms of c-Met upregulation in PDAC cells. We established GEM-resistant and radioresistant PDAC cells to analyze the transcriptome involved in c-Met expression. The microarray data for the established radiation-resistant PDAC cells indicated miR-181b-5p downregulation, which targets ETS1, one of the transcription factors for c-Met, and it was shown that radiation exposure induced c-Met expression through ETS1 increase by the suppression of miR-181b-5p. These results suggested that targeting these mechanisms may promote the development of a novel multidisciplinary treatment strategy for improving preoperative CRT efficiency.

  10. Dual Embeddedness of Governance and Strategy-Analysis Based on Interlocking Directorate Network%治理与战略的双重嵌入性——基于连锁董事网络的研究

    Institute of Scientific and Technical Information of China (English)

    郑方

    2011-01-01

    迄今为止,连锁董事网络效应方面的研究还存在着很大的分歧。本文打开连锁董事网络运作的“黑箱”,以可以消除分歧的嵌入性视角进行分析.认为连锁董事网络嵌入实质上体现了治理与战略的双重嵌入性,是以连锁董事网络为载体.通过连锁董事社会资本到企业社会资本的内化,以治理与战略的整合作用而产生效应的.并因嵌入惰性和嵌入寻租而存在过度嵌入陷阱。为了不囿于连锁董事研究,本文进行了扩展性分析.探讨企业社会关系的“差序格局”和嵌入层次,以及三层次嵌入下的关系治理与网络战略.在此基础上,认为可以将嵌入的本质收益和成本理解为社会资本和社会责任.而社会责任可分为保健型和激励型两类,分别起到维持和提升社会资本的作用.并针对连锁董事网络制度设计等问题提出了相关建议.%So far, there are differences on interlocking directorate network eiffel. This paper opened the black box of interlocking directorate network, taking the perspective of embeddedness, which can eliminate differences. Interlocking directorate network embeddedness embodies double embeddedness of corporate governanee and strategy in essence, and it takes network as carrier, having effect though social capital from individual to enterprise and integrated action of corporate governance and strategy. And it is constrained within the moderate embeddedness. In order not to be limited to interlocking directorate study, extended analysis was taken in this paper, discussing the enterprise's Chaxu pattern of social relationship, embeddedness levels and corporate relational governance and network strategy under three-level embeddedness. On this basis, this paper considered social capital and social responsibility as benefit and cost of embeddedness, social responsibility can be divided into motivation and hygiene, which taking

  11. Elevated expression of circulating miR876-5p is a specific response to severe EV71 infections.

    Science.gov (United States)

    Wang, Robert Y L; Weng, Kuo-Feng; Huang, Yhu-Chering; Chen, Chih-Jung

    2016-01-01

    Human enterovirus 71 (EV71) is a major causative agent of hand, foot, and, mouth disease, accounting for more than 65% of recent outbreaks. Following enteroviral infection, the host responses are crucial indicators for the development of a diagnosis regarding the clinical severity of EV71 infections. In this study, we implemented NanoString nCounter technology to characterize the responses of serum microRNA (miRNA) profiles to various EV71 infection diseases. Upon EV71 infection, 44 miRNAs were observed in patients with EV71 infections, with at least a 2-fold elevation and 133 miRNAs with a 2-fold reduction compared with the same miRNAs in healthy controls. Further detailed work with miR876-5p, a 9.5-fold change of upregulated miR-876-5p expression was observed in cases with severe EV71 symptoms, revealed that in vitro and in vivo knockdown of miR876-5p reduced viral RNA in cultured cells, and attenuated the severity of symptoms in EV71-infected mice. Altogether, we demonstrated that the elevated expression of circulating miR876-5p is a specific response to severe EV71 infections.

  12. Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer

    NARCIS (Netherlands)

    R.L. Milne (Roger); E.L. Goode (Ellen); M. García-Closas (Montserrat); F.J. Couch (Fergus); G. Severi (Gianluca); R. Hein (Rebecca); Z. Fredericksen (Zachary); N. Malats (Núria); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); J. Benítez (Javier); T. Dörk (Thilo); P. Schürmann (Peter); J.H. Karstens (Johann); P. Hillemanns (Peter); A. Cox (Angela); I.W. Brock (Ian); K.S. Elliot (Katherine); S.S. Cross (Simon); S. Seal (Sheila); C. Turnbull (Clare); A. Renwick (Anthony); N. Rahman (Nazneen); C-Y. Shen (Chen-Yang); J-C. Yu (Jyh-Cherng); C.-S. Huang (Chiun-Sheng); M.-F. Hou (Ming-Feng); B.G. Nordestgaard (Børge); S.E. Bojesen (Stig); C. Lanng (Charlotte); G.G. Alnæs (Grethe); V. Kristensen (Vessela); A.-L. Børrensen-Dale (Anne-Lise); J.L. Hopper (John); G.S. Dite (Gillian); C. Apicella (Carmel); M.C. Southey (Melissa); D. Lambrechts (Diether); B.T. Yesilyurt (Betül); O.A.M. Floris; K. Leunen; S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); J. Chang-Claude (Jenny); S. Wang-Gohrke (Shan); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); G.G. Giles (Graham); L. Baglietto (Laura); E.M. John (Esther); A. Miron (Alexander); S.J. Chanock (Stephen); J. Lissowska (Jolanta); M.E. Sherman (Mark); J.D. Figueroa (Jonine); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); I.V. Zalutsky (Iosif); Y.I. Rogov (Yuri); P.A. Fasching (Peter); T. Bayer (T.); A.B. Ekici (Arif); M.W. Beckmann (Matthias); H. Brenner (Hermann); H. Müller (Heike); V. Arndt (Volker); C. Stegmaier (Christa); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); A. Meindl (Alfons); J. Heil (Joerg); C.R. Bartram (Claus); R.K. Schmutzler (Rita); G. Thomas (Gilles); R.N. Hoover (Robert); O. Fletcher (Olivia); L.J. Gibson (Lorna); I. dos Santos Silva (Isabel); J. Peto (Julian); S. Nickels (Stefan); D. Flesch-Janys (Dieter); H. Anton-Culver (Hoda); A. Ziogas (Argyrios); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); R.A.E.M. Tollenaar (Rob); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); K.A. Pooley (Karen); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); B. Burwinkel (Barbara); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); D. Kang (Daehee); K-Y. Yoo (Keun-Young); D-Y. Noh (Dong-Young); S.-H. Ahn (Sei-Hyun); D. Hunter (David); S.E. Hankinson (Susan); P. Kraft (Peter); S. Lindstrom (Stephen); X. Chen (Xiaoqing); J. Beesley (Jonathan); U. Hamann (Ute); V. Harth (Volker); C. Justenhoven (Christina); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); R.A. Oldenburg (Rogier); M.M.A. Tilanus-Linthorst (Madeleine); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofieva (Darya); A. Farahtdinova (Albina); J.E. Olson (Janet); X. Wang (Xing); M.K. Humphreys (Manjeet); Q. Wang (Qing); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas)

    2011-01-01

    textabstractBackground: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer A

  13. Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

    NARCIS (Netherlands)

    Milne, Roger L.; Goode, Ellen L.; Garca-Closas, Montserrat; Couch, Fergus J.; Severi, Gianluca; Hein, Rebecca; Fredericksen, Zachary; Malats, Nuria; Pilar Zamora, M.; Arias Perez, Jose Ignacio; Benitez, Javier; Doerk, Thilo; Schuermann, Peter; Karstens, Johann H.; Hillemanns, Peter; Cox, Angela; Brock, Ian W.; Elliot, Graeme; Cross, Simon S.; Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Rahman, Nazneen; Shen, Chen-Yang; Yu, Jyh-Cherng; Huang, Chiun-Sheng; Hou, Ming-Feng; Nordestgaard, Borge G.; Bojesen, Stig E.; Lanng, Charlotte; Alnaes, Grethe Grenaker; Kristensen, Vessela; Borrensen-Dale, Anne-Lise; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Lambrechts, Diether; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Chang-Claude, Jenny; Wang-Gohrke, Shan; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Giles, Graham G.; Baglietto, Laura; John, Esther M.; Miron, Alexander; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Figueroa, Jonine D.; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Zalutsky, Iosif V.; Rogov, Yuri I.; Fasching, Peter A.; Bayer, Christian M.; Ekici, Arif B.; Beckmann, Matthias W.; Brenner, Hermann; Mueller, Heiko; Arndt, Volker; Stegmaier, Christa; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Meindl, Alfons; Heil, Joerg; Bartram, Claus R.; Schmutzler, Rita K.; Thomas, Gilles D.; Hoover, Robert N.; Fletcher, Olivia; Gibson, Lorna J.; Silva, Isabel dos Santos; Peto, Julian; Nickels, Stefan; Flesch-Janys, Dieter; Anton-Culver, Hoda; Ziogas, Argyrios; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Tollenaar, Rob A. E. M.; Pharoah, Paul D. P.; Dunning, Alison M.; Pooley, Karen A.; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Hunter, David J.; Hankinson, Susan E.; Kraft, Peter; Lindstrom, Sara; Chen, Xiaoqing; Beesley, Jonathan; Hamann, Ute; Harth, Volker; Justenhoven, Christina; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje; Hollestelle, Antoinette; Oldenburg, Rogier A.; Tilanus-Linthorst, Madeleine; Khusnutdinova, Elza; Bermisheva, Marina; Prokofieva, Darya; Farahtdinova, Albina; Olson, Janet E.; Wang, Xianshu; Humphreys, Manjeet K.; Wang, Qin; Chenevix-Trench, Georgia; Easton, Douglas F.

    2011-01-01

    Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association C

  14. Significance of the class II hydrophobin FgHyd5p for the life cycle of Fusarium graminearum.

    Science.gov (United States)

    Minenko, Ekaterina; Vogel, Rudi F; Niessen, Ludwig

    2014-04-01

    Hydrophobins are small secreted proteins ubiquitously found in filamentous fungi. Some hydrophobins were shown to have functions in fungal development, while others lack known function. Class II hydrophobins from Fusarium graminearum and Fusarium culmorum are characterized by formation of low stability aggregates and their solubility in organic solvents. They are economically relevant to the brewing industry because they can induce beer gushing. Since cellular functions of Hyd5p's are still unknown, we analyzed the influence of FgHyd5p on growth and morphology of F. graminearum using FgΔhyd5 knock-out mutants expressing sGFP under the control of the hyd5 promoter and compared them with the performance of the parent wild type strain. Results demonstrate that FgHyd5p does not affect the colony and hyphal morphology. FgHyd5p affects the hydrophobicity of aerial mycelia but had no obvious function in penetration of hyphae through the water air interface. The hydrophobin affects the morphology of conidia, but not their fitness. Different sources of carbon and nitrogen as well as different pH have no effect on the expression of the hyd5 gene, which was demonstrated to be expressed upon growth of F. graminearum on hydrophobic surfaces.

  15. Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases.

    Science.gov (United States)

    Eramo, Matthew J; Mitchell, Christina A

    2016-02-01

    The phosphoinositide 3-kinase (PI3K) generated lipid signals, PtdIns(3,4,5)P3 and PtdIns(3,4)P2, are both required for the maximal activation of the serine/threonine kinase proto-oncogene Akt. The inositol polyphosphate 5-phosphatases (5-phosphatases) hydrolyse the 5-position phosphate from the inositol head group of PtdIns(3,4,5)P3 to yield PtdIns(3,4)P2. Extensive work has revealed several 5-phosphatases inhibit PI3K-driven Akt signalling, by decreasing PtdIns(3,4,5)P3 despite increasing cellular levels of PtdIns(3,4)P2. The roles that 5-phosphatases play in suppressing cell proliferation and transformation are slow to emerge; however, the 5-phosphatase PIPP [proline-rich inositol polyphosphate 5-phosphatase; inositol polyphosphate 5-phosphatase (INPP5J)] has recently been identified as a putative tumour suppressor in melanoma and breast cancer and SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] inhibits haematopoietic cell proliferation. INPP5E regulates cilia stability and INPP5E mutations have been implicated ciliopathy syndromes. This review will examine 5-phosphatase regulation of PI3K/Akt signalling, focussing on the role PtdIns(3,4,5)P3 5-phosphatases play in developmental diseases and cancer.

  16. Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

    DEFF Research Database (Denmark)

    Milne, Roger L; Goode, Ellen L; García-Closas, Montserrat;

    2011-01-01

    BACKGROUND: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Associatio...

  17. HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13

    DEFF Research Database (Denmark)

    Asad, Samina; Nikamo, Pernilla; Gyllenberg, Alexandra;

    2012-01-01

    We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD≤2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D...... susceptibility genes....

  18. Quantitative Analyses of Force-Induced Amyloid Formation in Candida albicans Als5p: Activation by Standard Laboratory Procedures.

    Directory of Open Access Journals (Sweden)

    Cho X J Chan

    Full Text Available Candida albicans adhesins have amyloid-forming sequences. In Als5p, these amyloid sequences cluster cell surface adhesins to create high avidity surface adhesion nanodomains. Such nanodomains form after force is applied to the cell surface by atomic force microscopy or laminar flow. Here we report centrifuging and resuspending S. cerevisiae cells expressing Als5p led to 1.7-fold increase in initial rate of adhesion to ligand coated beads. Furthermore, mechanical stress from vortex-mixing of Als5p cells or C. albicans cells also induced additional formation of amyloid nanodomains and consequent activation of adhesion. Vortex-mixing for 60 seconds increased the initial rate of adhesion 1.6-fold. The effects of vortex-mixing were replicated in heat-killed cells as well. Activation was accompanied by increases in thioflavin T cell surface fluorescence measured by flow cytometry or by confocal microscopy. There was no adhesion activation in cells expressing amyloid-impaired Als5pV326N or in cells incubated with inhibitory concentrations of anti-amyloid dyes. Together these results demonstrated the activation of cell surface amyloid nanodomains in yeast expressing Als adhesins, and further delineate the forces that can activate adhesion in vivo. Consequently there is quantitative support for the hypothesis that amyloid forming adhesins act as both force sensors and effectors.

  19. miR-339-5p regulates the p53 tumor-suppressor pathway by targeting MDM2

    DEFF Research Database (Denmark)

    Jansson, M D; Djodji Damas, Nkerorema; Lees, M

    2014-01-01

    MicroRNAs (miRNAs) regulate many key cancer-relevant pathways and may themselves possess oncogenic or tumor-suppressor functions. Consequently, miRNA dysregulation has been shown to be a prominent feature in many human cancers. The p53 tumor suppressor acts as a negative regulator of cell...... proliferation in response to stress and represents the most commonly lost and mutated gene in human cancers. The function of p53 is inhibited by the MDM2 oncoprotein. Using a high-throughput screening approach, we identified miR-339-5p as a regulator of the p53 pathway. We demonstrate that this regulation...... inhibition of miR-339-5p function perturbs the p53 response in cancer cells, allowing an increased proliferation rate. In addition, miR-339-5p expression is downregulated in tumors harboring wild-type TP53, suggesting that reduction of miR-339-5p level helps to suppress the p53 response in p53-competent...

  20. Impact of spaceborne carbon monoxide observations from the S-5P platform on tropospheric composition analyses and forecasts

    Science.gov (United States)

    Abida, Rachid; Attié, Jean-Luc; El Amraoui, Laaziz; Ricaud, Philippe; Lahoz, William; Eskes, Henk; Segers, Arjo; Curier, Lyana; de Haan, Johan; Kujanpää, Jukka; Oude Nijhuis, Albert; Tamminen, Johanna; Timmermans, Renske; Veefkind, Pepijn

    2017-01-01

    We use the technique of Observing System Simulation Experiments (OSSEs) to quantify the impact of spaceborne carbon monoxide (CO) total column observations from the Sentinel-5 Precursor (S-5P) platform on tropospheric analyses and forecasts. We focus on Europe for the period of northern summer 2003, when there was a severe heat wave episode associated with extremely hot and dry weather conditions. We describe different elements of the OSSE: (i) the nature run (NR), i.e., the truth; (ii) the CO synthetic observations; (iii) the assimilation run (AR), where we assimilate the observations of interest; (iv) the control run (CR), in this study a free model run without assimilation; and (v) efforts to establish the fidelity of the OSSE results. Comparison of the results from AR and the CR, against the NR, shows that CO total column observations from S-5P provide a significant benefit (at the 99 % confidence level) at the surface, with the largest benefit occurring over land in regions far away from emission sources. Furthermore, the S-5P CO total column observations are able to capture phenomena such as the forest fires that occurred in Portugal during northern summer 2003. These results provide evidence of the benefit of S-5P observations for monitoring processes contributing to atmospheric pollution.

  1. A new governance space for health.

    Science.gov (United States)

    Kickbusch, Ilona; Szabo, Martina Marianna Cassar

    2014-01-01

    Global health refers to 'those health issues which transcend national boundaries and governments and call for actions on the global forces and global flows that determine the health of people'. (Kickbusch 2006) Governance in this trans-national and cross-cutting arena can be analyzed along three political spaces: global health governance, global governance for health, and governance for global health. It is argued that the management of the interface between these three political spaces of governance in the global public health domain is becoming increasingly important in order to move the global health agenda forward. Global health governance refers mainly to those institutions and processes of governance which are related to an explicit health mandate, such as the World Health Organization; global governance for health refers mainly to those institutions and processes of global governance which have a direct and indirect health impact, such as the United Nations, World Trade Organization or the Human Rights Council; governance for global health refers to the institutions and mechanisms established at the national and regional level to contribute to global health governance and/or to governance for global health--such as national global health strategies or regional strategies for global health. It can also refer to club strategies, such as agreements by a group of countries such as the BRICS. In all three political spaces, the involvement of a multitude of state and non-state actors has become the norm--that is why issues of legitimacy, accountability and transparency have moved to the fore. The transnational nature of global health will require the engagement of all actors to produce global public goods for health (GPGH) and to ensure a rules-based and reliably financed global public health domain.

  2. Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2016-05-01

    Full Text Available Background/Aims: Qiliqiangxin (QL, a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h. The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP, brain natriuretic peptide (BNP, and β-myosin heavy chain (MYH7 were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL

  3. Pension Fund governing board

    CERN Document Server

    HR Department

    2008-01-01

    On 16 March and 7 May, the Pension Fund Governing Board (PFGB) held its fourth and fifth meetings The first of these meetings was primarily dedicated to the examination of the strategic asset allocation. The PFGB reaffirmed the main goal of the new strategic asset allocation: to improve the Pension Fund’s position with regard to risk by lowering overall portfolio volatility through suitable investments in less volatile asset classes such as real estate and absolute return strategies, where the return does not depend on market trends and negative growth is extremely unlikely. The finalised document will be presented to the Finance Committee and the Council at their June meetings for approval, in accordance with the provisions of the Levaux report. The PFGB also took note of the Internal Audit’s report on Pension Fund operations and decided to refer it to Working Group I as a working document for establishing a control and internal monitoring system for Pension Fund oper...

  4. Between Democracy and Governance

    DEFF Research Database (Denmark)

    Bang, Henrik

    2015-01-01

    The work of Gerry Stoker and Colin Hay considers the alliance between neoliberalism and public choice theory to be the motor of anti-politics and depoliticization in contemporary Western societies. Their effects have been to hollow out strong statecraft and hard state capacity, as well as the thick...... collective capacities for representation, participation and deliberation crucial to keeping democratic government responsive, effective and accountable to the common will. On this view, all new forms of connective action are ipso facto rejected as the spawn of neoliberalism: They appear as individualistic...... and preventing the much needed repoliticizations that can bring the old, strong combination of hard state power and thickly integrated citizenship back in. I do not think this type of politicization strategy will work. There are good reasons why it has fizzled out over time. New forms of political participation...

  5. Website Quality in Government

    DEFF Research Database (Denmark)

    Sørum, Hanne; Andersen, Kim Normann; Clemmensen, Torkil

    2013-01-01

    Purpose – The objective of this paper is to investigate how webmasters within government bodies explain quality of websites. Despite the central position for advancing the communication, bridging usability tests and design, there are surprisingly few studies on how webmasters perceive, experience...... and explain website quality or design issues. Design/methodology/approach – The authors' unit of analysis is webmasters from Norwegian web-award-winning organizations. Eight webmasters from four types of websites were interviewed. The websites were purposefully sampled, using the strategy of maximal variation...... sampling to maximize difference between the four types of websites. Findings – The findings reveal that issues concerning usability are found to be an important dimension of website quality. The authors' analysis of how webmasters explain website quality reveals substantial variance in explanation...

  6. Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis.

    Science.gov (United States)

    Khan, Shenaz; Abu Jawdeh, Bassam G; Goel, Monu; Schilling, William P; Parker, Mark D; Puchowicz, Michelle A; Yadav, Satya P; Harris, Raymond C; El-Meanawy, Ashraf; Hoshi, Malcolm; Shinlapawittayatorn, Krekwit; Deschênes, Isabelle; Ficker, Eckhard; Schelling, Jeffrey R

    2014-03-01

    Chronic kidney disease progression can be predicted based on the degree of tubular atrophy, which is the result of proximal tubule apoptosis. The Na+/H+ exchanger NHE1 regulates proximal tubule cell survival through interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but pathophysiologic triggers for NHE1 inactivation are unknown. Because glomerular injury permits proximal tubule luminal exposure and reabsorption of fatty acid/albumin complexes, we hypothesized that accumulation of amphipathic, long-chain acyl-CoA (LC-CoA) metabolites stimulates lipoapoptosis by competing with the structurally similar PI(4,5)P2 for NHE1 binding. Kidneys from mouse models of progressive, albuminuric kidney disease exhibited increased fatty acids, LC-CoAs, and caspase-2-dependent proximal tubule lipoapoptosis. LC-CoAs and the cytosolic domain of NHE1 directly interacted, with an affinity comparable to that of the PI(4,5)P2-NHE1 interaction, and competing LC-CoAs disrupted binding of the NHE1 cytosolic tail to PI(4,5)P2. Inhibition of LC-CoA catabolism reduced NHE1 activity and enhanced apoptosis, whereas inhibition of proximal tubule LC-CoA generation preserved NHE1 activity and protected against apoptosis. Our data indicate that albuminuria/lipiduria enhances lipotoxin delivery to the proximal tubule and accumulation of LC-CoAs contributes to tubular atrophy by severing the NHE1-PI(4,5)P2 interaction, thereby lowering the apoptotic threshold. Furthermore, these data suggest that NHE1 functions as a metabolic sensor for lipotoxicity.

  7. Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients

    Science.gov (United States)

    Jeong, Sohyun; Oh, Jung Mi

    2017-01-01

    Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development. PMID:28152049

  8. miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype.

    Science.gov (United States)

    Tommasi, Stefania; Pinto, Rosamaria; Danza, Katia; Pilato, Brunella; Palumbo, Orazio; Micale, Lucia; De Summa, Simona

    2016-12-06

    In recent years, the assessment of biomarkers useful for "precision medicine" has been a hot topic in research. The involvement of microRNAs in the pathogenesis of breast cancer has been highly investigated with the aim of being able to molecularly stratify this highly heterogeneous disease. Our aim was to identify microRNAs targeting DNA repair machinery, through Affymetrix GeneChip miRNA Arrays, in a cohort of BRCA-related and sporadic breast cancers. Moreover, we analyzed microRNA expression taking into account our previous results on the expression of PARP1, because of its importance in targeted therapy. miR-361-5p and miR-151-5p were found to be overexpressed in PARP1-upregulating BRCA-germline mutated and sporadic breast tumors. Pathway enrichment analysis was performed to identify potential target genes to be analyzed in the validation step in an independent cohort. Our results confirmed the overexpression of miR-151-5p and, interestingly, its role in the targeting of SMARCA5, a chromatin remodeler. This result was also confirmed in vitro, both through luciferase assay and by analyzing endogenous levels of SMARCA5 in MCF-7 cell lines using miR-151-5p mimic and inhibitor. In conclusion, our data showed the possibility of considering the overexpression of PARP1 and miR-151-5p as biomarkers useful to correctly treat sporadic breast cancers, which eventually could be considered as BRCAness tumors, with PARP-inhibitors.

  9. Voluntary Environmental Governance Arrangements

    NARCIS (Netherlands)

    van der Heijden, J.

    2012-01-01

    Voluntary environmental governance arrangements have focal attention in studies on environmental policy, regulation and governance. The four major debates in the contemporary literature on voluntary environmental governance arrangements are studied. The literature falls short of sufficiently specify

  10. Business Climate and Good Governance

    Directory of Open Access Journals (Sweden)

    Besmira Manaj

    2015-03-01

    Full Text Available This paper consists of three factors, namely: Good Governance, Business Climate and Corruption. How they affect the development product of Albania, not only as a concept, and a principle but mostly as a sensitive aspect in the integration process. There are some interpretations of this concept, but I intend to analyze the key factors and actors, their cooperation and concrete production in society. Improving governance is necessary to have an integrated long term strategy based upon a continuous cooperation between institutions and citizens. But in developing countries like Albania there are some important questions such as: How can we measure the improvement of Good Governance through policies? Has Good Governance indicated an effective way for the sustainable development? (Meisel, 2008, 6. These question give us the orientation to reflect about the process of development, social economic political behavior and how this multidimensional is transformed in product of good governance. The business cycle is strongly connected with many aspects of political-, social-, juridical aspects and good governance. Despite attempts to draft law regulations, the level of corruption and informality in Albania continues to be a major obstacle. The credibility level in the implementation of law is an indicator that affects democratization and institutional integration. At present, different reports of international institutions, define Albania as the country with the highest level of Corruption in the Balkans, which is a key factor influencing business. The ways with

  11. 基于5P4F的电子商务模式创新方法研究%5P4F-based Innovation Method of E-Commerce Business Models

    Institute of Scientific and Technical Information of China (English)

    方孜; 王刊良

    2002-01-01

    互联网的发展为商务模式创新开辟了广阔空间和自由度,持续创新是电子商务模式与生俱来的本质.亚马逊等商务模式在美国专利与商标局获得专利极大地刺激了商务模式创新活动.本文提出了基于5P4F(5P指Product、Price、Place、Promotion和Potion;4F指business flow、information flow、capital flow和logistics flow)的电子商务模式的分析方法,提出了基于5P4F的企业电子商务模式创新方法.

  12. VT Certified Local Governments

    Data.gov (United States)

    Vermont Center for Geographic Information — Vermont established its Certified Local Government (CLG) program in 1985 to better help local governments integrate historic preservation concerns with planning and...

  13. Multivalent benzene polyphosphate derivatives are non-Ca(2+)-mobilizing Ins(1,4,5)P3 receptor antagonists.

    Science.gov (United States)

    Mills, Stephen J; Luyten, Tomas; Erneux, Christophe; Parys, Jan B; Potter, Barry V L

    2012-12-01

    Inositol 1,4,5-trisphosphate [Ins(1,4,5)P31] mobilizes intracellular Ca(2+) through the Ins(1,4,5)P3 receptor [InsP3R]. Although some progress has been made in the design of synthetic InsP3R partial agonists and antagonists, there are still few examples of useful small molecule competitive antagonists. A "multivalent" approach is explored and new dimeric polyphosphorylated aromatic derivatives were designed, synthesized and biologically evaluated. The established weak InsP3R ligand benzene 1,2,4-trisphosphate [Bz(1,2,4)P32] is dimerized through its 5-position in two different ways, first directly as the biphenyl derivative biphenyl 2,2',4,4',5,5'-hexakisphosphate, [BiPh(2,2',4,4',5,5')P68] and with its regioisomeric biphenyl 3,3',4,4',5,5'-hexakisphosphate [BiPh(3,3',4,4',5,5')P611]. Secondly, a linker motif is introduced in a flexible ethylene-bridged dimer (9) with its corresponding 1,2-bisphosphate dimer (10), both loosely analogous to the very weak antagonist 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA 7). In permeabilized L15 fibroblasts overexpressing type 1 InsP3R, BiPh(2,2',4,4',5,5')P6 (8) inhibits Ins(1,4,5)P3-induced Ca(2+) release in a apparently competitive fashion [IC50 187 nM] and the Bz(1,2,4)P3 dimer (9) is only slightly weaker [IC50 380 nM]. Compounds were also evaluated against type I Ins(1,4,5)P3 5-phosphatase. All compounds are resistant to dephosphorylation, with BiPh(2,2',4,4',5,5')P6 (8), being the most effective inhibitor of any biphenyl derivative synthesized to date [IC50 480 nM] and the Bz(1,2,4)P3 ethylene dimer (9) weaker [IC50 3.55 μM]. BiPh(3,3',4,4',5,5')P6 (11) also inhibits 5-phosphatase [IC50 730 nM] and exhibits unexpected Ca(2+) releasing activity [EC50 800 nM]. Thus, relocation of only a single mirrored phenyl phosphate group in (11) from that of antagonist (8) does not markedly change enzyme inhibitory activity, but elicits a dramatic switch in Ca(2+)-releasing activity. Such new agents demonstrate the

  14. MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation.

    Science.gov (United States)

    Iwasaki, Kenta; Yamamoto, Takayuki; Inanaga, Yukiko; Hiramitsu, Takahisa; Miwa, Yuko; Murotani, Kenta; Narumi, Shuji; Watarai, Yoshihiko; Katayama, Akio; Uchida, Kazuharu; Kobayashi, Takaaki

    2017-02-01

    De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p biomarkers to evaluate immune response and kidney allograft status.

  15. 基于政府补贴分析的新能源战略博弈模型研究%Research on New Energy Strategy Game Model based on Government Subsidies

    Institute of Scientific and Technical Information of China (English)

    蔡伟琨; 贾磊丽; 张聪

    2012-01-01

    In the new energy strategy,if we don't choose the development of new energy strategy,the cost savings ε1 the higher,the lower the marginal cost of C1,and the differences in price of new energy products and traditional products are bigger.With the increase of consumer satisfaction for the environment-care are willing to pay the value of "K",with the result,both the two products,prices will increase.In other words,with increasing consumer awareness of environmental protection,environmental satisfaction,willingness to pay will increase.Such a result is not only good for manufacturers who use the new energy,but good for manufacturers who not use the new energy.Government to increase the market the lowest green degree of access standards,the low green degree of traditional products and new energy product prices will increase.And it affect the market share of market.%企业在新能源战略中如果不发展新能源战略带来的成本节约率ε1越高,其边际成本C1越低,新能源产品和传统产品的价格差异越大。随着消费者对每个环境满意度愿意支付的K值的增加,两个厂商的产品价格都会增加,也就是说,随着消费者环保意识的增加,环境满意度支付意愿也会增加,这样的结果不仅仅是生产新能源的厂商2受益,厂商1也会受益;政府提高市场最低绿色程度准入标准,低绿色程度的传统产品和新能源产品的价格都会增加。政府设定的市场最低绿色准入标准会对两个厂商的市场份额有影响。

  16. New directions in hospital governance.

    Science.gov (United States)

    Shortell, S M

    1989-01-01

    This article suggests new directions for hospital governance to meet the demands of a rapidly changing health care environment. Board members must increasingly play roles as risk takers, strategic directors, experts, mentors, and evaluators. Lessons from other industries regarding risk taking, use of expertise, and streamlining decision making must be adapted to meet hospital needs. Recent data suggest that these needs may still differ by hospital ownership despite a convergence in investor-owned and not-for-profit corporate structures. The effectiveness of hospital boards in the future will depend on their ability to: (1) manage a diverse group of stakeholders; (2) involve physicians in the management and governance process; (3) meet the governance needs of multi-institutional systems and hospital restructuring; (4) meet the challenges of diversification and vertical integration; and (5) understand strategy formulation and implementation as interdependent and interrelated processes.

  17. The Politics of Governance Architectures

    DEFF Research Database (Denmark)

    Borrás, Susana; Radaelli, Claudio M.

    2011-01-01

    Governance architectures are strategic and long-term institutional arrangements of international organizations exhibiting three features; namely, they address strategic and long-term problems in a holistic manner, they set substantive output-oriented goals, and they are implemented through...... not being identified as an object of study on its own right. We define the Lisbon Strategy as a case of governance architecture, raising questions about its creation, evolution and impact at the national level. We tackle these questions by drawing on institutional theories about emergence and change...... of institutional arrangements and on the multiple streams model. We formulate a set of propositions and hypotheses to make sense of the creation, evolution and national impact of the Lisbon Strategy. We argue that institutional ambiguity is used strategically by coalitions at the EU and national level in (re...

  18. A Quantitative Trait Locus on Chromosome 5p Influences D-Dimer Levels in the San Antonio Family Heart Study

    Directory of Open Access Journals (Sweden)

    V. P. Diego

    2010-01-01

    D-dimer levels were normalized in our study. We found that D-dimer levels were heritable, at about 23% heritability (P≈.00001. In a linkage analysis employing 432 microsatellite markers, we found strong evidence of a QTL on chromosome 5p with a lod score of 3.32 at 21 centiMorgans (cM. We also found suggestive evidence of a QTL on chromosome 2q with a lod score of 2.33 at 207 cM. Conclusions. To our knowledge, the putative QTL on chromosome 5p is novel. The possible QTL on chromosome 2q is discussed in relation to a recent report of linkage of a related hemostatic factor to the same location. These results warrant further investigation.

  19. miR-31 and miR-17-5p levels change during transformation of follicular lymphoma.

    Science.gov (United States)

    Thompson, Mary Ann; Edmonds, Mick D; Liang, Shan; McClintock-Treep, Sara; Wang, Xuan; Li, Shaoying; Eischen, Christine M

    2016-04-01

    The 30% of patients whose indolent follicular lymphoma transforms to aggressive diffuse large B-cell lymphoma (DLBCL) have poor survival. Reliable predictors of follicular B-cell lymphoma transformation to DLBCL are lacking, and diagnosis of those that will progress is challenging. MicroRNA, which regulates gene expression, has critical functions in the growth and progression of many cancers and contributes to the pathogenesis of lymphoma. Using 5 paired samples from patients who presented with follicular lymphoma and progressed to DLBCL, we identified specific microRNA differentially expressed between the two. Specifically, miR-17-5p levels were low in follicular lymphoma and increased as the disease transformed. In contrast, miR-31 expression was high in follicular lymphoma and decreased as the lymphoma progressed. These results were confirmed in additional unpaired cases of low-grade follicular lymphoma (n = 13) and high-grade follicular lymphoma grade 3 or DLBCL (n = 17). Loss of miR-31 expression in DLBCL was not due to deletion of the locus. Changes in miR-17-5p and miR-31 were not correlated with immunophenotype, genetics, or status of the MYC oncogene. However, increased miR-17-5p expression did significantly correlate with increased expression of p53 protein, which is indicative of mutant TP53. Two pro-proliferative genes, E2F2 and PI3KC2A, were identified as direct messenger RNA targets of miR-31, suggesting that these may contribute to follicular lymphoma transformation. Our results indicate that changes in miR-31 and miR-17-5p reflect the transformation of follicular lymphoma to an aggressive large B-cell lymphoma and may, along with their targets, be viable markers for this process.

  20. Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

    DEFF Research Database (Denmark)

    Milne, Roger L; Goode, Ellen L; García-Closas, Montserrat

    2011-01-01

    and histopathology were assessed using logistic regression. RESULTS: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive...

  1. Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels.

    Science.gov (United States)

    Dai, Gucan; Yu, Haijie; Kruse, Martin; Traynor-Kaplan, Alexis; Hille, Bertil

    2016-06-07

    Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na(+)/myo-inositol cotransporter (SMIT1) and myo-inositol supplementation enlarged intracellular PI(4,5)P2 pools, modulated several PI(4,5)P2-dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycin-recruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myo-inositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several "physiological" manipulations that alter the PI(4,5)P2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells.

  2. Audit Methodology for IT Governance

    Directory of Open Access Journals (Sweden)

    Mirela GHEORGHE

    2010-01-01

    Full Text Available The continuous development of the new IT technologies was followed up by a rapid integration of them at the organization level. The management of the organizations face a new challenge: structural redefinition of the IT component in order to create plus value and to minimize IT risks through an efficient management of all IT resources of the organization. These changes have had a great impact on the governance of the IT component. The paper proposes an audit methodology of the IT Governance at the organization level. From this point of view the developed audit strategy is a strategy based on risks to enable IT auditor to study from the best angle efficiency and effectiveness of the IT Governance structure. The evaluation of the risks associated with IT Governance is a key process in planning the audit mission which will allow the identification of the segments with increased risks. With now ambition for completeness, the proposed methodology provides the auditor a useful tool in the accomplishment of his mission.

  3. Cloning and characterization of Arabidopsis thaliana AtNAP57--a homologue of yeast pseudouridine synthase Cbf5p.

    Science.gov (United States)

    Maceluch, J; Kmieciak, M; Szweykowska-Kulińska, Z; Jarmołowski, A

    2001-01-01

    Rat Nap57 and its yeast homologue Cbf5p are pseudouridine synthases involved in rRNA biogenesis, localized in the nucleolus. These proteins, together with H/ACA class of snoRNAs compose snoRNP particles, in which snoRNA guides the synthase to direct site-specific pseudouridylation of rRNA. In this paper we present an Arabidopsis thaliana protein that is highly homologous to Cbf5p (72% identity and 85% homology) and NAP57 (67% identity and 81% homology). Moreover, the plant protein has conserved structural motifs that are characteristic features of pseudouridine synthases of the TruB class. We have named the cloned and characterized protein AtNAP57 (Arabidopsis thaliana homologue of NAP57). AtNAP57 is a 565 amino-acid protein and its calculated molecular mass is 63 kDa. The protein is encoded by a single copy gene located on chromosome 3 of the A. thaliana genome. Interestingly, the AtNAP57 gene does not contain any introns. Mutations in the human DKC1 gene encoding dyskerin (human homologue of yeast Cbf5p and rat NAP57) cause dyskeratosis congenita a rare inherited bone marrow failure syndrome characterized by abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia.

  4. Host PI(3,5)P2 activity is required for Plasmodium berghei growth during liver stage infection.

    Science.gov (United States)

    Thieleke-Matos, Carolina; da Silva, Mafalda Lopes; Cabrita-Santos, Laura; Pires, Cristiana F; Ramalho, José S; Ikonomov, Ognian; Seixas, Elsa; Shisheva, Assia; Seabra, Miguel C; Barral, Duarte C

    2014-10-01

    Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5-kinase (PIKfyve) that converts phosphatidylinositol 3-phosphate [PI(3)P] into phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2 ] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non-pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.

  5. Governance, Government, and the Search for New Provider Models.

    Science.gov (United States)

    Saltman, Richard B; Duran, Antonio

    2015-11-03

    A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory) perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome.

  6. Metropolitan Governance Reforms: The Case of Seoul Metropolitan Government

    Directory of Open Access Journals (Sweden)

    Nicholas Snyder

    2012-10-01

    Full Text Available Seoul is transforming into a global city that is competitive with many of the most notable cities in the world such as Tokyo, New York, and London. Seoul’s metropolitan governance structure is uniquely suited to the Korean peninsula and has been able to be dynamic in order to adapt to political changes the country has experienced. This article examines the initiatives behind metropolitan governance reforms in Seoul and the factors that play an important role in influencing the current governance structure. The Seoul Metropolitan Government (SMG is set on improving the lives of citizens and ensuring they are happy with their city through transparency, accountability, efficiency, and effectiveness of government among other things. This region has become a strong contributor to the economic growth of the county and helped to create opportunities to attract and retain businesses, implement innovative investment projects and develop a talented workforce. Amongst other reasons, Seoul’s solid fiscal system has allowed the city to build the necessary organizational capacity for SMG as well. Additionally, Seoul citizens enjoy a good quality of life because of the educational options, employment opportunities, housing spaces, leisure activities, and cultural experiences found in the city. There are still some challenges ahead but Seoul realizes the importance of civic participation for capacity building and sustainability. One of Seoul’s strategies to promoting sustainable living within the city is its ability to engage the public. By promoting citizen participation and feedback, Seoul feels that it will gain new perceptivities during the policy decision-making process. The city’s current governance methods continue to succeed because the leaders at SMG understand what is essential to executing successful governance reform: citizens.

  7. Metropolitan Governance Reforms: The Case of Seoul Metropolitan Government

    Directory of Open Access Journals (Sweden)

    Nicholas Snyder

    2016-02-01

    Full Text Available Seoul is transforming into a global city that is competitive with many of the most notable cities in the world such as Tokyo, New York, and London. Seoul's metropolitan governance structure is uniquely suited to the Korean peninsula and has been able to be dynamic in order to adapt to political changes the country has experienced. This article examines the initiatives behind metropolitan governance reforms in Seoul and the factors that play an important role in influencing the current governance structure. The Seoul Metropolitan Government (SMG is set on improving the lives of citizens and ensuring they are happy with their city through transparency, accountability, efficiency, and effectiveness of government among other things. This region has become a strong contributor to the economic growth of the county and helped to create opportunities to attract and retain businesses, implement innovative investment projects and develop a talented workforce. Amongst other reasons, Seoul's solid fiscal system has allowed the city to build the necessary organizational capacity for SMG as well. Additionally, Seoul citizens enjoy a good quality of life because of the educational options, employment opportunities, housing spaces, leisure activities, and cultural experiences found in the city. There are still some challenges ahead but Seoul realizes the importance of civic participation for capacity building and sustainability. One of Seoul's strategies to promoting sustainable living within the city is its ability to engage the public. By promoting citizen participation and feedback, Seoul feels that it will gain new perceptivities during the policy decision-making process. The city's current governance methods continue to succeed because the leaders at SMG understand what is essential to executing successful governance reform: citizens.

  8. Governance, Government, and the Search for New Provider Models

    Directory of Open Access Journals (Sweden)

    Richard B. Saltman

    2016-01-01

    Full Text Available A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome.

  9. 知识型中小企业创新生态系统治理策略研究%Research on Governance Strategy of Innovation Ecosystem in Small and Medium-sized Knowledge Enterprises

    Institute of Scientific and Technical Information of China (English)

    陈建斌; 高书丽; 郭彦丽

    2016-01-01

    activities to guarantee "mass innovation" . This is the core industry governance strategy for SMEK system.

  10. Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and plasma membrane.

    Science.gov (United States)

    Feng, Xinghua; Huang, Yu; Lu, Yungang; Xiong, Jian; Wong, Ching-On; Yang, Pu; Xia, Jintang; Chen, De; Du, Guangwei; Venkatachalam, Kartik; Xia, Xuefeng; Zhu, Michael X

    2014-02-14

    Transient Receptor Potential mucolipin (TRPML) channels are implicated in endolysosomal trafficking, lysosomal Ca(2+) and Fe(2+) release, lysosomal biogenesis, and autophagy. Mutations in human TRPML1 cause the lysosome storage disease, mucolipidosis type IV (MLIV). Unlike vertebrates, which express three TRPML genes, TRPML1-3, the Drosophila genome encodes a single trpml gene. Although the trpml-deficient flies exhibit cellular defects similar to those in mammalian TRPML1 mutants, the biophysical properties of Drosophila TRPML channel remained uncharacterized. Here, we show that transgenic expression of human TRPML1 in the neurons of Drosophila trpml mutants partially suppressed the pupal lethality phenotype. When expressed in HEK293 cells, Drosophila TRPML was localized in both endolysosomes and plasma membrane and was activated by phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) applied to the cytoplasmic side in whole lysosomes and inside-out patches excised from plasma membrane. The PI(3,5)P2-evoked currents were blocked by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but not other phosphoinositides. Using TRPML A487P, which mimics the varitint-waddler (Va) mutant of mouse TRPML3 with constitutive whole-cell currents, we show that TRPML is biphasically regulated by extracytosolic pH, with an optimal pH about 0.6 pH unit higher than that of human TRPML1. In addition to monovalent cations, TRPML exhibits high permeability to Ca(2+), Mn(2+), and Fe(2+), but not Fe(3+). The TRPML currents were inhibited by trivalent cations Fe(3+), La(3+), and Gd(3+). These features resemble more closely to mammalian TRPML1 than TRPML2 and TRPML3, but with some obvious differences. Together, our data support the use of Drosophila for assessing functional significance of TRPML1 in cell physiology.

  11. Decolorization mechanism of molasses wastewater by Aspergillus flavus A5p1%黄曲霉A5p1脱色糖蜜酒精废水机理初探

    Institute of Scientific and Technical Information of China (English)

    贺锴; 何小慧; 李必金; 邹成; 覃益民; 李青云; 刘幽燕

    2014-01-01

    研究自行筛选的一株黄曲霉( Aspergillus flavus) A5p1(保藏号CGMCC.4292)对糖蜜酒精废水( MSW)的脱色机理.在外加蔗糖情况下菌株A5p1对MSW具有较好的脱色效果,脱色率由14%增高至58%;脱色进程与细胞生长基本同步.从培养液中检测出3种木质素过氧化物酶---漆酶( Lac)及两种胞外过氧化物酶即锰过氧化物酶( MnP )和不依赖锰的过氧化物酶( MiP )的酶活,但是水平不高,认为此3种酶不是主要的脱色机制.发现由各种代谢过程产生的总H2 O2生成速率与脱色率基本同步,同时在第4天达到最大值,随后下降;还原糖总消耗也在初期阶段较快.外加蔗糖后总H2 O2生成速率增加10倍,达到0.0027 mmol·min-1·mL-1.认为体系中脱色机制可能与产H2 O2的酶相关.紫外可见光谱分析和凝胶色谱分析表明脱色过程中有大分子物质降解.综上所述初步认为,黄曲霉A5p1脱色糖蜜酒精废水是一个受产H2 O2酶影响、复杂的生物降解过程.%The decolorization mechanism of molasses wastewater ( MSW) by Aspergillus flavus A5P1 ( CGMCC.4292) was studied in this article. With the addition of sucrose, strain A5P1 displayed a better decolorization activity, and the decolorization rate increased from 14% to 58%. The cell dry weight was synchronized with the change of decolorization rate. Three lignin peroxidases relevant to the biodecolorization were detected in the culture fluid, including laccase and two extracellular peroxidases, a manganese-independent peroxidase ( MiP ) and manganese peroxidase ( MnP ) , but, with low activity. It is deducted that these three enzymes did not play a leading role in the the MSW-decolorization by the strain. The total generation rate of H2 O2 from a variety of metabolic processes was found to be synchronous to the decolorization rate, both reaching maximum after 4 d and decreasing subsequently. The total

  12. Radiation hardness of Ga0.5In0.5 P/GaAs tandem solar cells

    Science.gov (United States)

    Kurtz, Sarah R.; Olson, J. M.; Bertness, K. A.; Friedman, D. J.; Kibbler, A.; Cavicchi, B. T.; Krut, D. D.

    1991-01-01

    The radiation hardness of a two-junction monolithic Ga sub 0.5 In sub 0.5 P/GaAs cell with tunnel junction interconnect was investigated. Related single junction cells were also studied to identify the origins of the radiation losses. The optimal design of the cell is discussed. The air mass efficiency of an optimized tandem cell after irradiation with 10(exp 15) cm (-2) 1 MeV electrons is estimated to be 20 percent using currently available technology.

  13. The discharge mode transition and O(5p1) production mechanism of pulsed radio frequency capacitively coupled plasma

    Science.gov (United States)

    Liu, X. Y.; Hu, J. T.; Liu, J. H.; Xiong, Z. L.; Liu, D. W.; Lu, X. P.; Shi, J. J.

    2012-07-01

    The discharge mode transition from uniform plasma across the gas gap to the α mode happens at the rising phase of the pulsed radio frequency capacitively coupled plasma (PRF CCP). This transition is attributed to the fast increasing stochastic heating at the edge of sheath. In the second stage with the stable current and voltage amplitude, the consistency between experimental and numerical spatial-temporal 777 nm emission profile suggests that He* and He2* dominate the production of O(5p1) through dissociation and excitation of O2. Finally, the sterilization efficiency of PRF CCP is found to be higher than that of plasma jet.

  14. Governance of disaster risk reduction in Cameroon: The need to empower local government

    Directory of Open Access Journals (Sweden)

    Henry N. Bang

    2013-01-01

    Full Text Available The impact of natural hazards and/or disasters in Cameroon continues to hit local communities hardest, but local government lacks the ability to manage disaster risks adequately. This is partly due to the fact that the necessity to mainstream disaster risk reduction into local governance and development practices is not yet an underlying principle of Cameroon’s disaster management framework. Using empirical and secondary data, this paper analyses the governance of disaster risks in Cameroon with particular focus on the challenges local government faces in implementing disaster risk reduction strategies. The hypothesis is that the governance of disaster risks is too centralised at the national level, with huge implications for the effective governance of disaster risks at the local level. Although Cameroon has reinvigorated efforts to address growing disaster risks in a proactive way, it is argued that the practical actions are more reactive than proactive in nature. The overall aim is to explore the challenges and opportunities that local government has in the governance of disaster risks. Based on the findings from this research, policy recommendations are suggested on ways to mainstream disaster risk reduction strategies into local governance, and advance understanding and practice in the local governance of disaster risks in the country.

  15. Nordic Corporate Governance Revisited

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2016-01-01

    This paper reviews the key elements of the Nordic governance model, which include a distinct legal system, high governance ratings and low levels of corruption. Other characteristics include concentrated ownership, foundation ownership, semi two-tier board structures, employee representation...

  16. Government and Business

    DEFF Research Database (Denmark)

    Campbell, John L.

    2015-01-01

    There is a vast literature about the relationships between government and business in advanced capitalist societies.......There is a vast literature about the relationships between government and business in advanced capitalist societies....

  17. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

    Directory of Open Access Journals (Sweden)

    Fuencisla Matesanz

    Full Text Available Multiple Sclerosis (MS is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9. This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

  18. Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

    Science.gov (United States)

    Sanna, Serena; Gayán, Javier; Urcelay, Elena; Zara, Ilenia; Pitzalis, Maristella; Cavanillas, María L.; Arroyo, Rafael; Zoledziewska, Magdalena; Marrosu, Marisa; Fernández, Oscar; Leyva, Laura; Alcina, Antonio; Fedetz, Maria; Moreno-Rey, Concha; Velasco, Juan; Real, Luis M.; Ruiz-Peña, Juan Luis; Cucca, Francesco

    2012-01-01

    Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS. PMID:22570697

  19. The iA{beta}5p {beta}-breaker peptide regulates the A{beta}(25-35) interaction with lipid bilayers through a cholesterol-mediated mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Vitiello, Giuseppe [Department of Chemistry, University of Naples ' Federico II' , Naples (Italy); CSGI (Consorzio per lo Sviluppo dei Sistemi a Grande Interfase), Florence (Italy); Grimaldi, Manuela; D' Ursi, Anna Maria [Department of Pharmaceutical Science, University of Salerno, Fisciano (Italy); D' Errico, Gerardino, E-mail: gerardino.derrico@unina.it [Department of Chemistry, University of Naples ' Federico II' , Naples (Italy); CSGI (Consorzio per lo Sviluppo dei Sistemi a Grande Interfase), Florence (Italy)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer iA{beta}5p shows a significant tendency to deeply penetrates the hydrophobic core of lipid membrane. Black-Right-Pointing-Pointer A{beta}(25-35) locates in the external region of the membrane causing a re-positioning of CHOL. Black-Right-Pointing-Pointer iA{beta}5p withholds cholesterol in the inner hydrophobic core of the lipid membrane. Black-Right-Pointing-Pointer iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane. -- Abstract: Alzheimer's disease is characterized by the deposition of aggregates of the {beta}-amyloid peptide (A{beta}) in the brain. A potential therapeutic strategy for Alzheimer's disease is the use of synthetic {beta}-sheet breaker peptides, which are capable of binding A{beta} but unable to become part of a {beta}-sheet structure, thus inhibiting the peptide aggregation. Many studies suggest that membranes play a key role in the A{beta} aggregation; consequently, it is strategic to investigate the interplay between {beta}-sheet breaker peptides and A{beta} in the presence of lipid bilayers. In this work, we focused on the effect of the {beta}-sheet breaker peptide acetyl-LPFFD-amide, iA{beta}5p, on the interaction of the A{beta}(25-35) fragment with lipid membranes, studied by Electron Spin Resonance spectroscopy, using spin-labeled membrane components (either phospholipids or cholesterol). The ESR results show that iA{beta}5p influences the A{beta}(25-35) interaction with the bilayer through a cholesterol-mediated mechanism: iA{beta}5p withholds cholesterol in the inner hydrophobic core of the bilayer, making the interfacial region more fluid and capable to accommodate A{beta}(25-35). As a consequence, iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane, which is the first step of the {beta}-amyloid aggregation process.

  20. SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells.

    Science.gov (United States)

    Elong Edimo, William's; Ghosh, Somadri; Derua, Rita; Janssens, Veerle; Waelkens, Etienne; Vanderwinden, Jean-Marie; Robe, Pierre; Erneux, Christophe

    2016-03-15

    Phosphoinositides, particularly phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], are recognized by SHIP2 (also known as INPPL1) a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the preferred SHIP2 substrate is PI(3,4,5)P3, PI(4,5)P2 can also be dephosphorylated by this enzyme to phosphatidylinositol 4-phosphate (PI4P). Through depletion of SHIP2 in the glioblastoma cell line 1321 N1, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In 1321 N1 cells, the PI(4,5)P2-binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls 1321 N1 cell migration through the organization of focal adhesions. Thus, our results reveal a new role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma 1321 N1 cells.

  1. Big Bad Governance.

    Science.gov (United States)

    Richardson, James T.

    1999-01-01

    Argues that the Association of Governing Boards of Universities and Colleges' statement on governance calls for more centralized authority, rejecting both the principles and the practice of shared governance and diminishing the role of faculty. Suggests that the association revise its statement to include a better understanding of how academe…

  2. Why Governments Intervene

    DEFF Research Database (Denmark)

    Knudsen, Jette Steen; Brown, Dana

    2015-01-01

    Why are national governments increasingly adopting policies on corporate social responsibility (CSR)? Government CSR policies have been explained either as a means of substituting or supporting (mirroring) domestic political-economic institutions and policies, or as a means for government to prom...

  3. Global water governance

    NARCIS (Netherlands)

    Gupta, J.; Falkner, R.

    2013-01-01

    Although (fresh) water challenges are primarily local in nature, globalization has led to feedback effects that make many water challenges global in nature. This chapter examines global water governance. It discusses four phases of water governance, argues that water governance is dispersed and inco

  4. Transformative environmental governance

    Science.gov (United States)

    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to ...

  5. Project governance: selected South African government experiments

    Directory of Open Access Journals (Sweden)

    G. van der Walt

    2008-07-01

    Full Text Available Some form of accountability and power structure binds all organisations. Such structures are typically referred to as the “governance” structure of the organisation. In organisations that have relatively mature project applications and methodologies in place, governance mechanisms are established on more permanent bases. With its focus on performance, results and outcomes, project governance establishes decision-making structures, as well as accountability and responsibility mechanisms in public institutions to oversee projects. As government institutions increasingly place emphasis on project applications for policy implementation and service delivery initiatives, mechanisms or structures should be established to facilitate clear interfaces between the permanent organisation and the temporary project organisation. Such mechanisms or structures should enhance the governance of projects, that is, the strategic alignment of projects, the decentralisation of decision- making powers, rapid resource allocation, and the participation of external stakeholders. The purpose of this article is to explore the concept “project governance”, and to highlight examples of project governance as applied in selected government departments in provincial and national spheres. This would enable the establishment of best practice examples and assist to develop benchmarks for effective project applications for service delivery improvement.

  6. miR-204-5p acts as a tumor suppressor by targeting matrix metalloproteinases-9 and B-cell lymphoma-2 in malignant melanoma

    Science.gov (United States)

    Luan, Wenkang; Qian, Yao; Ni, Xin; Bu, Xuefeng; Xia, Yun; Wang, Jinlong; Ruan, Hongru; Ma, Shaojun; Xu, Bin

    2017-01-01

    An increasing number of microRNAs have been found to be involved in tumorigenesis, including melanoma tumorigenesis. miR-204-5p is down-regulated and functions as a tumor suppressor in many human malignant tumors. miR-204-5p expression is also decreased in melanoma tissues, but its biological roles and molecular mechanisms in malignant melanoma remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in melanoma, especially in metastatic melanoma. miR-204-5p also served as a protective factor for the prognosis of melanoma patients. We determined that miR-204-5p suppresses cell proliferation, migration and invasion, and promotes cell apoptosis in melanoma. Matrix metalloproteinases-9 and B-cell lymphoma-2 are the functional targets of miR-204-5p, through which it plays an important biological role in malignant melanoma. The effect of miR-204-5p on malignant melanoma is verified using a xenograft model. We also determined that miR-204-5p increases 5-fluorouracil and cisplatin (DDP) chemosensitivity in malignant melanoma cells. This finding elucidates new functions and mechanisms for miR-204-5p in melanoma development, and provides potential therapeutic targets for the treatment of melanoma.

  7. Government Public Service Advertising Design

    Directory of Open Access Journals (Sweden)

    Agus Ganjar Runtiko

    2013-07-01

    Full Text Available Public service advertising is one of the government strategies to promote the development program. At the national level, the government prefers television as a medium for advertising. As for the local level, the government usually tend to choose lower-cost ads. In Banyumas, many public service announcements using outdoor media such as billboards, banners, or posters. Characteristics of outdoor media that promotes design in attracting the attention of an audience became a challenge for designers. On the other hand, the messages also require the space in public service announcements. This study wants to know about how the execution of the design of outdoor advertising services in the community in efforts to combine the design with a message to be delivered. The study, sought to examine aspects of the design using the composition interpretation methods and verbal composition of outdoor advertising with discourse analysis methods.This research concludes that the government public service announcements desain still needs to be improved according to the rules of visual communication design.

  8. E-government value priorities of Danish local authority managers

    OpenAIRE

    Rose, Jeremy; Persson, John Stouby

    2012-01-01

    The management of eGovernment is a central topic in the improvement of public administration, where the underlying values of eGovernment practitioners are an important (but often taken for granted) motivation for strategy and implementation of eGovernment projects. This chapter offers a value analysis of central trends in the public administration literature: New Public Management, the post-Weberian Bureaucracy and the New Public Service. Using the assumption that eGovernment is driven largel...

  9. Institutional Impacts of the Local Government Reform Program on Good Local Governance in Tanzania

    Directory of Open Access Journals (Sweden)

    Boniface E.S. Mgonja

    2012-05-01

    Full Text Available Ever since the early 1990s, Tanzania’s government has embarked upon ambitious and far-reaching reform programs to improve the socioeconomic condition of the country. Among them was the development of anti-corruption strategies and the local government reform program. Overall, these reform programs were expected to improve good governance through reformed and autonomous local institutions. As such, this paper provides a detailed analysis of two reform initiatives, namely, anti-corruption strategies and LGRP based on their main policy goals as well as impacts on the overall institutional performance of local institutions in Tanzania. Drawing upon review of some empirical studies, the paper discusses what is seen as major structural concerns in the workings of these reforms in their entirety. This paper builds on the proposition that, unless someone addresses “institutional shortfalls” within the greater system of governance, any policy or reform initiative aimed at improving good governance will ultimately fail to deliver.

  10. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    LENUS (Irish Health Repository)

    Bibby, Becky A S

    2015-01-01

    Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA\\/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1\\/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1\\/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of

  11. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Becky A S Bibby

    Full Text Available Oesophageal adenocarcinoma (OAC is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil. In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the

  12. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    Science.gov (United States)

    Bibby, Becky A S; Reynolds, John V; Maher, Stephen G

    2015-01-01

    Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of mi

  13. Hard and Soft Governance

    DEFF Research Database (Denmark)

    Moos, Lejf

    2009-01-01

    and discusses governance forms at several levels. The first layer is the global: the methods of 'soft governance' that are being utilised by transnational agencies. The second layer is the national and local: the shift in national and local governance seen in many countries, but here demonstrated in the case......The governance and leadership at transnational, national and school level seem to be converging into a number of isomorphic forms as we see a tendency towards substituting 'hard' forms of governance, that are legally binding, with 'soft' forms based on persuasion and advice. This article analyses...... of Denmark, and finally the third layer: the leadership used in Danish schools. The use of 'soft governance' is shifting the focus of governance and leadership from decisions towards influence and power and thus shifting the focus of the processes from the decision-making itself towards more focus...

  14. miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway

    Science.gov (United States)

    Shen, Bo; Yu, Shaorong; Zhang, Yan; Yuan, Yuan; Li, Xiaoyou; Zhong, Jian; Feng, Jifeng

    2016-01-01

    Background The aim of this study was to determine the role of miRNA-590-5p in gastric cancer (GC) progression. Methods Quantitative real-time polymerase chain reaction was performed to measure endogenous miR-590-5p levels in GC cells and tissues. Overexpression or knockdown of miR-590-5p in GC cells was performed by transfection with mimics or an inhibitor, respectively. MTT, matrigel transwell, and Western blot assays were used to assess the effects of miR-590-5p on cell proliferation, invasion, chemosensitivity of GC cells, and the AKT pathway, respectively. In silico prediction and luciferase reporter activity were used to identify potential targets of miR-590-5p. A xenograft model was also established to evaluate the function of miR-590-5p in vivo. Results The expression of miR-590-5p was significantly increased in GC cells and tissues, and upregulated miR-590-5p was associated with increased tumor size, lymph node metastasis, and poor survival. Overexpression of miR-590-5p promoted cell proliferation and invasion and reduced the sensitivity of GC cells to cisplatin and paclitaxel. In contrast, inhibition of miR-590-5p had the opposite effects on GC cells. RECK was identified as a direct target of miR-590-5p. Knockdown of RECK accelerated cell proliferation and motility and decreased the drug sensitivity. Furthermore, reintroduction of RECK inhibited the oncogenic effects of miR-590-5p by suppressing cell proliferation and invasion and increasing drug sensitivity. We found that the AKT/ERK and STAT3 signaling pathways were activated by miR-590-5p overexpression. The chemoresistance of miR-590-5p was also verified by in vivo analysis. Conclusion In summary, we suggest that the miR-590-5p/RECK/AKT axis contributes to GC and may serve as a promising therapeutic target for treatment. PMID:27757042

  15. MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6(STAT6)

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dachuang [Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province 210009 (China); Department of Urology, Xuzhou Central Hospital Affiliated with Southeast University, Xuzhou, Jiangsu Province 221009 (China); Surgery Central Laboratory of Southeast University, Nanjing, Jiangsu Province 210009 (China); Tao, Tao; Xu, Bin; Chen, Shuqiu; Liu, Chunhui [Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province 210009 (China); Surgery Central Laboratory of Southeast University, Nanjing, Jiangsu Province 210009 (China); Zhang, Lei; Lu, Kai [Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province 210009 (China); Huang, Yeqing; Jiang, Liang [Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province 210009 (China); Surgery Central Laboratory of Southeast University, Nanjing, Jiangsu Province 210009 (China); Zhang, Xiaowen [Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province 210009 (China); Huang, Xiaoming [Surgery Central Laboratory of Southeast University, Nanjing, Jiangsu Province 210009 (China); Zhang, Lihua [Department of Pathology, Zhongda Hospital Affiliated with Southeast University, Nanjing, Jiangsu Province 210009 (China); Han, Conghui [Department of Urology, Xuzhou Central Hospital Affiliated with Southeast University, Xuzhou, Jiangsu Province 221009 (China); Chen, Ming, E-mail: mingchenseu@gmail.com [Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province 210009 (China); Surgery Central Laboratory of Southeast University, Nanjing, Jiangsu Province 210009 (China)

    2014-02-28

    Highlights: • The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. • We found that the expression of miR-361-5p in CRPC was lower than in ADPC. • MiR-361-5p suppressed DU145 cell proliferation and triggered apoptosis. • STAT6 is a direct target of miR-361-5p. • STAT6 enhances the expression of Bcl-xL at the transcriptional level. - Abstract: Castration-resistant prostate cancer (CRPC), whose pathogenesis is known to be regulated by microRNAs (miRNAs), has a poor prognosis. In our present study, we found that the expression of miR-361-5p in CRPC was lower than in androgen-dependent prostate cancer (ADPC), indicating that miR-361-5p may play an important role in the progression of ADPC to CRPC. The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. Our findings suggest that miR-361-5p is a suppressor in CRPC. Signal transducer and activator of transcription-6 (STAT6), a direct target of miR-361-5p, enhances the expression of B-cell lymphoma-extra large (Bcl-xL), while miR-361-5p inhibits its expression through STAT6. Therefore, miR-361-5p has great clinical significance in preventing the malignant progression of PCa.

  16. Arranged marriage in lipid signalling? The limited choices of PtdIns(4,5)P2 in finding the right partner.

    Science.gov (United States)

    Heilmann, M; Heilmann, I

    2013-09-01

    Inositol-containing phospholipids (phosphoinositides, PIs) control numerous cellular processes in eukaryotic cells. For plants, a key involvement of PIs has been demonstrated in the regulation of membrane trafficking, cytoskeletal dynamics and in processes mediating the adaptation to changing environmental conditions. Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)) mediates its cellular functions via binding to various alternative target proteins. Such downstream targets of PtdIns(4,5)P(2) are characterised by the possession of specific lipid-binding domains, and binding of the PtdIns(4,5)P(2) ligand exerts effects on their activity or localisation. The large number of potential alternative binding partners - and associated cellular processes - raises the question how alternative or even contrapuntal effects of PtdIns(4,5)P(2) are orchestrated to enable cellular function. This article aims to provide an overview of recent insights and new views on how distinct functional pools of PtdIns(4,5)P(2) are generated and maintained. The emerging picture suggests that PtdIns(4,5)P(2) species containing different fatty acids influence the lateral mobility of the lipids in the membrane, possibly enabling specific interactions of PtdIns(4,5)P(2) pools with certain downstream targets. PtdIns(4,5)P(2) pools with certain functions might also be defined by protein-protein interactions of PI4P 5-kinases, which pass PtdIns(4,5)P(2) only to certain downstream partners. Individually or in combination, PtdIns(4,5)P(2) species and specific protein-protein interactions of PI4P 5-kinases might contribute to the channelling of PtdIns(4,5)P(2) signals towards specific functional effects. The dynamic nature of PI-dependent signalling complexes with specific functions is an added challenge for future studies of plant PI signalling.

  17. RESEARCH ON BEHAVIORS OF GOVERNMENT'S TOURISM MARKETING

    Directory of Open Access Journals (Sweden)

    Shan Quian

    2010-06-01

    Full Text Available Tourism has become one of the world's largest industries with broad prospects and large industrial scale. In tourism marketing, planning and packaging the image of destinations, promotion,and participating in nonprofit marketing have become inevitable choice of all levels of governments. This paper firstly discusses inevitability and necessity of government tourism marketing, and then analyzing their roles. On these basis,paper discusses the strategy of the implementation of government tourism marketing, respectively, promoting the image, location, destination organization, and information technology support.

  18. Molecular determinants of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding to transient receptor potential V1 (TRPV1) channels.

    Science.gov (United States)

    Poblete, Horacio; Oyarzún, Ingrid; Olivero, Pablo; Comer, Jeffrey; Zuñiga, Matías; Sepulveda, Romina V; Báez-Nieto, David; González Leon, Carlos; González-Nilo, Fernando; Latorre, Ramón

    2015-01-23

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain receptor activated by a wide range of stimuli. However, whether or not PI(4,5)P2 is a TRPV1 agonist remains open to debate. Utilizing a combined approach of mutagenesis and molecular modeling, we identified a PI(4,5)P2 binding site located between the TRP box and the S4-S5 linker. At this site, PI(4,5)P2 interacts with the amino acid residues Arg-575 and Arg-579 in the S4-S5 linker and with Lys-694 in the TRP box. We confirmed that PI(4,5)P2 behaves as a channel agonist and found that Arg-575, Arg-579, and Lys-694 mutations to alanine reduce PI(4,5)P2 binding affinity. Additionally, in silico mutations R575A, R579A, and K694A showed that the reduction in binding affinity results from the delocalization of PI(4,5)P2 in the binding pocket. Molecular dynamics simulations indicate that PI(4,5)P2 binding induces conformational rearrangements of the structure formed by S6 and the TRP domain, which cause an opening of the lower TRPV1 channel gate.

  19. A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence

    DEFF Research Database (Denmark)

    Kooistra, Susanne Marije; Rudkjær, Lise Christine; Lees, Michael James

    2014-01-01

    -associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We...

  20. 5P Marketing Strategy on Sodium Diacetate Used as Feed Additive%饲料添加剂双乙酸钠的5P营销策略

    Institute of Scientific and Technical Information of China (English)

    谢清若; 郑立文; 李克林; 凌新龙

    2011-01-01

    基于产品(product)、价格(price)、地点(place)和推广(promotion)等市场营销4P策略的内容,结合双乙酸钠的特征、应用和市场现状,整合融入营销平台(platform),即从4P策略过渡到5P策略,并对双乙酸钠市场营销的5P策略实施进行了分析与探讨.

  1. A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence

    DEFF Research Database (Denmark)

    Kooistra, Susanne Marije; Rudkjær, Lise Christine; Lees, Michael James;

    2014-01-01

    fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16INK4A and senescence......-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We...... speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA....

  2. CORPORATE GOVERNANCE IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Ciprian Apostol

    2015-09-01

    Full Text Available The objective of the research was focused on measuring the performance level of corporate governance in Romania. This is carried out by evaluating the importance level given to the principles of corporate governance in the Romanian economy, while the practices of transparency and dissemination of companies’ information in the selected sample were monitored. To achieve the objectives of the study, we need to examine the Corporate Governance Code of the Bucharest Stock Exchange. Sample companies were selected and their information from the “Comply or Explain” Statements was analyzed.The research method is a non-participating observation—based on the information from the “Comply or Explain” Statement to determine whether companies are applying corporate governance and transparency elements. The research results highlight the progress of Romanian companies in the process of exercising to the principles of corporate governance, becoming internationally recognized, and integrating into the Corporate Governance Code of the Bucharest Stock Exchange.

  3. Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Lee, Kihwan; Kim, Hyunju; An, Kyongman; Kwon, Oh-Bin; Park, Sungjun; Cha, Jin Hee; Kim, Myoung-Hwan; Lee, Yoontae; Kim, Joung-Hun; Cho, Kwangwook; Kim, Hye-Sun

    2016-10-06

    MicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer's disease (AD). We found that oligomeric Aβ1-42 treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the reduction in dendritic spine density in the primary hippocampal neurons treated with oligomeric Aβ1-42 and cultured from 5XFAD mice. The reduction in the frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore, we found that miR-188 expression is CREB-dependent. Taken together, our results suggest that dysregulation of miR-188-5p expression contributes to the pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits associated with Aβ-mediated pathophysiology in the disease.

  4. MicroRNA-17-5p promotes gastric cancer proliferation, migration and invasion by directly targeting early growth response 2

    Science.gov (United States)

    Chen, Peng; Zhao, Huasi; Huang, Jingjing; Yan, Xizhong; Zhang, Yunfei; Gao, Yongshun

    2016-01-01

    MicroRNA-17-5p (miR-17-5p) has previously been reported to play an important role in tumor development and progression. However, it functions differently regarding different kinds of malignant tumor, and its role and mechanism in gastric cancer (GC) still lacks investigation. In this study, we detected the relationship between miR-17-5p and the development of GC by qRT-PCR, and it turned out that the level of miR-17-5p was significantly higher in GC patients than that in normal controls, and the aberrant expression of miR-17-5p was correlated with lymph node metastasis. After that, we examined the effect of miR-17-5p taking on the proliferation, apoptosis, migration and invasion of GC cells and the underlying mechanism. Experiments indicated that knockdown of miR-17-5p inhibited the proliferation, invasion and migration, while promoting apoptosis of SGC7901 cells. Early Growth Response 2 (EGR2) protein or mRNA levels were downregulated or upregulated after overexpression or knockdown of miR-17-5p, respectively. By using dual luciferase assay and Western blot, we identified EGR2 as a functional target of miR-17-5p. As far as we know, this could be the first study to demonstrate that miR-17-5p is associated with tumor stage of GC and that it could possibly become a new therapeutic method for the treatment of GC.

  5. Formation Mechanism and Governance Strategies of Overloading and Overrun based on Theory of Constraints%基于制约理论的超限超载形成机理与治理思路研究

    Institute of Scientific and Technical Information of China (English)

    陈红

    2012-01-01

    超限超载现象及治理是国内外公路运输管理研究的热点。运用制约理论对超限超载行为的产生、恶化及自加强机制进行分析,认为各利益相关主体对超限超载的支撑作用、监管缺失条件下治理者自由裁量权和选择性执法导致的寻租行为,都加强了运输者超限超载动机。对超限超载行为的治理,不仅要突出对超限超载运输者的治理,也要突出对政府治理行为代理人的治理。提出从超限超载系统的构成入手,从路上治理向源头治理和利益相关者治理转变,从阶段性治理向日常性、程序化治理转变,从行政手段治理为主向制度化治理转变,最终形成公路运输超限超载控制的长效机制。%Overloading and overrun phenomenon and governance has been a hotspot in the research of highway transportation management at home and abroad.This paper uses theory of constraints to analysis the production,degradation,self-strengthening mechanism of the overloading and overrun,and believes that the stakeholder supporting role in overloading and overrun,administer decision under the conditions of supervision lack,and rent-seeking behavior caused by selective law enforcement have all strengthened the transporters overload motivation.Overloading and overrun behavior governance,not only need to highlight the transporters on the overloading governance,but also highlight agents of the governance acts.The paper also proposed to start with the structure of the overloading and overrun system,transit from road management to source control and stakeholder governance,from stage management to routine and procedures governance,from administrative means mainly to institutional governance,finally forming the long effect mechanism to control the overloading and overrun.

  6. 审计问责视角下国家治理方略实现的路径选择%The Selection of Realization Paths of National Governance Strategy from the Perspective of Audit Accountability

    Institute of Scientific and Technical Information of China (English)

    陈淑芳; 曹政

    2012-01-01

    Governing based on determined responsibility in accordance with laws is the fundamental way to realize the target of national management in China.In an authoritarian society,national governance should be changed from limiting the power of government to clarify the responsibility of government.Being regarded as an important tool to realize sound management,audit accountability leads diversified subjects participating in accountability and helps in constructing government responsibility system,simultaneously,making a clear division of responsibilities in different governance levels.Audit accountability clearly clarifies the audit and audited relationship as a derivative contract of national governance.The successful performance of this contractual relationship needs to bring the instrumental rationality of audit accountability into play,expend and deepen it from three aspects: the breadth,depth and strength so as to achieving the path selection from "treating disease" to "preventing disease".%依法定责而治是中国国家治理目标实现的根本途径。在权力型社会中,国家治理应从限制政府权力转为明确政府责任。审计问责作为实现良治的重要工具,引导多元主体参与问责,构建政府责任体系并对不同层级提出明确的责任划分,将审计与被审计关系明确为国家治理的派生性契约。这一契约关系的顺利履行需要发挥审计问责的工具理性,并从广度、强度和力度三方面进行拓展及深化,从而实现从"治已病"走向"治未病"的路径。

  7. Governance and Socioeconomic Performance

    OpenAIRE

    Vītola, A; Šenfelde, M

    2012-01-01

    There are wide discussions on the causes of the differences in the economic performance. Recent studies have stressed out the crucial role of institutions – formal and informal constraints that shape human interaction. The aim of this article is to evaluate the influence of governance – traditions and institutions by which authority in a country is exercised –on the socioeconomic development. To measure the level of governance we used World Bank’s Worldwide Governance Indicators and such indi...

  8. Civil Society and Governance

    DEFF Research Database (Denmark)

    Hulgård, Lars

    An illustration of how important the relationship is between civil society anbd governance. A short historic journey with four snapshots of times and situations that have provided interesting evidence about the connection between civil society and governance. My goal for the short historic journey...... is to make clear and hopefully even verify that providing knowledge about the impact of civil society and citizens’ participation on governance is one of the most urgent research tasks in the current period of time....

  9. Governability in Contemporary Mexico

    OpenAIRE

    Leonardo Curzio Gutiérrez

    1998-01-01

    Given the difficulties to establish a concept of governability and the frequent ideological usage of the term, it is much more operative to turn to the principle of governability, in the broad sense, which supports itself on five pillars: the political legitimacy of the government, the governmental efficiency to attend to the demands of society, the existence of shared social project, the agreement with the principle special interest groups, and international viability. The analysis of the st...

  10. Exploring Knowledge Governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahoney, Joseph T

    Knowledge governance is characterized as a distinctive research subject, the understanding of which cuts across diverse fields in management. In particular, it represents an intersection of knowledge management, strategic management, and theories of the firm. Knowledge governance considers how...... deployment of governance mechanisms influences knowledge processes: sharing, retaining, and creating knowledge. We survey the papers in this volume of the special issue, and discuss the remaining research challenges....

  11. Energy Efficiency Governance: Handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This handbook has been written to assist EE practitioners, government officials and stakeholders to establish effective EE governance structures for their country. The handbook provides readers with relevant information in an accessible format that will help develop comprehensive and effective governance mechanisms. For each of the specific topics dealt with (see Figure 1 in the Handbook), the IEA offers guidelines for addressing issues, or directs readers to examples of how such issues have been dealt with by specific countries.

  12. 治理理论下的公交优先发展策略研究%Study on the Strategies for the Development of Public Transportation Priority in the light of Governance Theory

    Institute of Scientific and Technical Information of China (English)

    张汝峰; 左魏魏

    2009-01-01

    在社会治理背景下,优先发展公交是摆在人们面前的一项重大课题.借鉴治理和善治理论,实现公交优先发展,必须坚持和贯彻"政府主导、多方参与"的原则思路,形成良好的治理模式.政府主导即加强政府在公交发展中的主导地位,加快公交立法,并形成合理持续的资金支持机制;多方参与即形成包括规划、建设管理部门在内的共同互动的机制,为公交创造一个良好的发展环境.%Under the background of govemance theory,giving priority to develop public transportation is an important topic.In the light of governance theory,realizing the priority development of public transportation,we must insist on and carry out the principle of"the government leading,multilateral participation"to form a good governance mode.The government leading is to strengthen the government's leading role in the priority development of public transport, accelerate legislation, and set up a reasonable and continuous funding mechanism.Muhilateral Darticipation is to establish the mechanism of mutual interaction,including planning and construction management department,to create a good development environment for public transportation.

  13. Governance, Trust and Taxes

    DEFF Research Database (Denmark)

    Weihe, Guri; Joensen, E. Juanna Schröter

    This paper examines the role of social capital (trust) vis-à-vis the propensity of a country to be a tax haven. The empirical analysis corroborates that better governed countries have a higher ceteris paribus probability to be tax havens. However, social capital counteracts the effect of governance...... quality. This effect is so strong that the partial effect of governance quality is reversed for countries with the trust index in the top quartile – making these high trust countries less likely to be tax havens – even as governance quality is increased. Thus it is crucial to consider the interaction...

  14. Inhibition of MicroRNA-149-5p Induces Apoptosis of Acute Myeloid Leukemia Cell Line THP-1 by Targeting Fas Ligand (FASLG)

    Science.gov (United States)

    Tian, Peijun; Yan, Li

    2016-01-01

    Background This study was aimed to reveal the role of miR-149-5p in acute myeloid leukemia (AML) cells apoptosis and the possible mechanism involved. Material/Methods The expression of miR-149-5p in leukemia cell lines, as well as the blood and bone marrow (BM) samples from leukemia patients, were monitored by reverse-transcription polymerase chain reaction (RT-PCR). AML cell line THP-1 was transfected with miR-149-5p mimic or inhibitor, and then cell apoptosis was determined using the APO Percentage assay kit. The target of miR-149-5p was predicted by using the microRNA.org database, and verified by RT-PCR, Western blot, and Dual-Luciferase reporter assays. Further, small interfering RNA (siRNA) against the target gene was co-transfected with miR-149-5p inhibitor, and then the cell apoptosis and the expression of apoptosis-related proteins were assessed. Results MiR-149-5p was significantly up-regulated in leukemia cell lines and samples from leukemia patients (P<0.01 or P<0.001), especially in THP-1 cells and samples from AML patients. Cell apoptosis was significantly decreased by miR-149-5p overexpression (P<0.01) and increased by miR-149-5p suppression (P<0.05). Fas Ligand (FASLG) was a direct target of miR-149-5p, and was negatively regulated by miR-149-5p. More importantly, the inductive effects of miR-149-5p suppression on cell apoptosis were abrogated by si-FASLG (P<0.01). Furthermore, the up-regulative effects of miR-149-5p suppression on the phosphorylated form of Fas-associated via death domain (p-FADD), caspase-8, caspase-2, caspase-3, and the cleaved forms of these caspases were abrogated by si-FASLG. Conclusions Inhibition of miR-149-5p can induce apoptosis in THP-1 cells. These inductive effects might be via targeting FASLG and activating FADD and caspases. PMID:28013316

  15. Network governance and capacity of local governments to deliver LED in Uganda

    Directory of Open Access Journals (Sweden)

    Rose B Namara

    2016-02-01

    Full Text Available This paper discusses network governance and its contribution to the capacity of local governments (LGs to deliver local economic development (LED in Uganda. Although a formal LED policy was only established in Uganda in February 2014, there have been LED-inspired practices in the past decade. Various scholars and practitioners have observed that the autonomy and capacity of LGs to deliver LED is limited, but have been hopeful that new governance strategies like network governance would increase the capacities of LGs. However, neither network governance arrangements among LGs, nor their potential to improve governance capacity, have been documented. In a case study of Kyenjojo District, this paper finds that existing network governance arrangements have been fundamental in improving financial autonomy at this LG, delivering some income to invest in LED activities, although no evidence was found of reduced transaction costs in transforming local economies. The study further reveals that network governance arrangements have not led to the development of specialised skills in regulation or law enforcement, and capacity gaps are evident amongst staff and members in understanding the private sector and how it works. On a positive note, there is clear evidence of attempts by the LG to be innovative. Based on these findings, this study recommends that LGs need to consider a multi-pronged or multi-network governance approach to LED, which in turn will require a refocusing of governance mechanisms to become more dynamic and responsive, and offer incentives to the various actors in the development sector.

  16. Self assembly of HIV-1 Gag protein on lipid membranes generates PI(4,5)P2/Cholesterol nanoclusters

    Science.gov (United States)

    Yandrapalli, Naresh; Lubart, Quentin; Tanwar, Hanumant S.; Picart, Catherine; Mak, Johnson; Muriaux, Delphine; Favard, Cyril

    2016-01-01

    The self-assembly of HIV-1 Gag polyprotein at the inner leaflet of the cell host plasma membrane is the key orchestrator of virus assembly. The binding between Gag and the plasma membrane is mediated by specific interaction of the Gag matrix domain and the PI(4,5)P2 lipid (PIP2). It is unknown whether this interaction could lead to local reorganization of the plasma membrane lipids. In this study, using model membranes, we examined the ability of Gag to segregate specific lipids upon self-assembly. We show for the first time that Gag self-assembly is responsible for the formation of PIP2 lipid nanoclusters, enriched in cholesterol but not in sphingomyelin. We also show that Gag mainly partition into liquid-disordered domains of these lipid membranes. Our work strongly suggests that, instead of targeting pre-existing plasma membrane lipid domains, Gag is more prone to generate PIP2/Cholesterol lipid nanodomains at the inner leaflet of the plasma membrane during early events of virus assembly. PMID:28008947

  17. Clinical significance of miR-140-5p and miR-193b expression in patients with breast cancer and relationship to IGFBP5

    Directory of Open Access Journals (Sweden)

    Gökçe Güllü

    2015-03-01

    Full Text Available The functional role of IGFBP5 in breast cancer is complicated. Experimental and bioinformatics studies have shown that IGFBP5 is targeted by miR-140-5p and miR-193b, although this has not yet been proven in clinical samples. The aim of this study was to evaluate the expression of miR-140-5p and miR-193b in breast cancer and adjacent normal tissue and assess its correlation with IGFBP5 and the clinicopathological characteristics of the tumors. IGFBP5 protein expression was analyzed immunohistochemically and IGFBP5, miR-140 and miR-193b mRNA expression levels were analyzed with real-time RT-PCR. Tumor tissue had higher miR-140-5p expression than adjacent normal tissue (p = 0.015. Samples with no immunohistochemical staining for IGFBP5 showed increased miR-140-5p expression (p = 0.009. miR-140-5p expression was elevated in invasive ductal carcinomas (p = 0.002, whereas basal-like tumors had decreased expression of miR-140-5p compared to other tumors (p = 0.008. Lymph node-positive samples showed an approximately 13-fold increase in miR-140-5p expression compared to lymph node-negative tissue (p = 0.049. These findings suggest that miR-140-5p, but not miR-193b, could be an important determinant of IGFBP5 expression and clinical phenotype in breast cancer patients. Further studies are needed to clarify the expressional regulation of IGFBP5 by miR-140-5p.

  18. Innovation in Governance

    NARCIS (Netherlands)

    Assche, van Kristof; Beunen, R.; Barba Lata, I.V.; Duineveld, M.

    2015-01-01

    In this chapter we develop a theoretical framework, deriving from the social systems theory of Niklas Luhmann and Evolutionary Governance Theory, to grasp the paradoxes of current notions of innovation in governance, and to outline an alternative approach. A renewed reflection on innovation we deem

  19. China and Global Governance

    Institute of Scientific and Technical Information of China (English)

    Wang Zaibang

    2007-01-01

    To enhance global governance has become more urgent with rapid development of globalization in the post-Cold War years. China has benefited from the process of globalization and hence should make greater contribution to the global governance in the future.

  20. The governance of adaptation

    NARCIS (Netherlands)

    Huitema, Dave; Adger, William Neil; Berkhout, Frans; Massey, Eric; Mazmanian, Daniel; Munaretto, Stefania; Plummer, Ryan; Termeer, Katrien

    2016-01-01

    The governance of climate adaptation involves the collective efforts of multiple societal actors to address problems, or to reap the benefits, associated with impacts of climate change. Governing involves the creation of institutions, rules and organizations, and the selection of normative princi

  1. Educational Governance in Denmark

    Science.gov (United States)

    Moos, Lejf

    2014-01-01

    Denmark has entered global competition by expanding collaboration with European countries, which is profoundly impacting the public sector and school governance. Relations between the state and institutions are transforming from traditional democratic, public-sector models of governance into new forms characterized as corporate and market-driven…

  2. Learning Democratic Global Governance.

    Science.gov (United States)

    Haavelsrud, Magnus

    1996-01-01

    Outlines a model process of developing knowledge from within different groups and cultures to allow more equitable participation of all world societies in the definition of global governance. Reviews concepts relevant to education's contributions toward learning and creating democratic global governance. Discusses the educational utility of…

  3. Global Governance, Educational Change

    Science.gov (United States)

    Mundy, Karen

    2007-01-01

    In the last half decade, a rising literature has focused on the idea that processes of economic, political and social globalization require analysis in terms of governance at the global level. It is argued in this article that emerging forms of global governance have produced significant challenges to conventional conceptions of international…

  4. Partnerships and Governance

    DEFF Research Database (Denmark)

    Damgaard, Bodil

    Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark.......Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark....

  5. Sizing the government

    NARCIS (Netherlands)

    de Witte, K.; Moesen, W.

    2009-01-01

    Is there such a thing as an optimal government size? We investigate by the non-parametric Data Envelopment Analysis (DEA) the so-called `Armey curve' which claims an inverted U-shaped relationship between government size and economic performance. The DEA scores are linked to control variables as ini

  6. Sizing the government

    NARCIS (Netherlands)

    de Witte, K.; Moesen, W.

    2010-01-01

    Is there such a thing as an optimal government size? We investigate the so-called Armey curve, which claims an inverted U-shaped relationship between government size and economic performance, using non-parametric Data Envelopment Analysis (DEA). The DEA scores are linked to control variables, such a

  7. The Iraqi Governing Council

    Science.gov (United States)

    Social Education, 2004

    2004-01-01

    This article provides the details of the chronological events surrounding the establishment of a Governing Council in Iraq in July 2003 by the United States, acting as the leader of the Coalition Provisional Authority (CPA) that administers Iraq. The following topics are discussed in the article: (1) The Composition of the Governing Council; (2)…

  8. Royal Ahold: A Failure Of Corporate Governance

    NARCIS (Netherlands)

    A. de Jong (Abe); D.V. DeJong; G.M.H. Mertens (Gerard); P.G.J. Roosenboom (Peter)

    2005-01-01

    textabstractRoyal Ahold (Koninklijke Ahold NV) was one of the major success stories in the 1990s and is one of the major failures in corporate governance, suffering a complete meltdown in 2003. This clinical study analyzes Ahold’s growth strategy through acquisitions and isolates the cause of the fa

  9. Decision Theory and the Governance of Technology.

    Science.gov (United States)

    Woodhouse, Edward J.

    1987-01-01

    Provides an overview of the decision making process for science and technology. Finds that government agencies and officials are not the major decision makers. Examines obstacles to achieving intelligent decisions when policy makers are scientists, business executives, and consumers. Concludes with five strategies for improving technological…

  10. Headquarters-subsidiary relationship governance in Poland

    NARCIS (Netherlands)

    Gusc, J.S.; Omta, S.W.F.

    2011-01-01

    The study addresses the views of agency and stewardship theory on governance of the relationship between headquarters and subsidiaries. It explores the influence of strategy, task environment and cultural differences on this relationship. The conceptual model is explored based on a survey of 76 poli

  11. Governance Mechanisms in Information Technology Outsourcing

    Science.gov (United States)

    Ravindran, Kiron

    2010-01-01

    While the dominance of Information Technology Outsourcing (ITO) as a sourcing strategy would seem to indicate successful and well-informed practice, frequent examples of unraveled engagements highlight the associated risks. Successful instances of outsourcing suggest that governance mechanisms effectively manage the related risks. This…

  12. On the Deliberative Dilemmas between the Government and the Civil Society in Chinese Local Governance——Based on the Chinese Macro-strategy of Democratization%中国地方治理中的政府与社会协商困境分析——基于民主化宏观策略的思考

    Institute of Scientific and Technical Information of China (English)

    杨守涛

    2012-01-01

    The national macro-strategy of democratization prescribes the fundamental direction and the core principles of democratization.The macro-strategy of democratization in China is positive but manageable,which causes many subjective and objective dilemmas to the deliberative practices between the government and the civil society in Chinese local governance.The local government can not do well in organizing deliberation,and it is difficult for the public to participate effectively.In order to solve these problems,it is necessary to overcome skepticism and build relevant mechanism to guarantee effective deliberation under the precondition of adhering the prudent and pragmatic strategy of democratization mentioned above.%一个国家民主化的宏观策略体现了该国民主化的根本方向与核心原则。中国民主化的宏观策略是一种可管理导向的积极民主化策略,这种策略给中国地方治理中的政府与社会协商实践造成了种种主客观困境,使得地方政府不能很好地举办协商活动,社会力量也不能有效地参与。为走出困境,就必须在坚持审慎而务实策略的同时,不断克服怀疑主义,建立和健全保证协商有效性的管理机制。

  13. Role of MiR-3619-5p in β-Catenin-Mediated Non-Small Cell Lung Cancer Growth and Invasion

    Directory of Open Access Journals (Sweden)

    Xuecai Niu

    2015-10-01

    Full Text Available Background/Aims: The malignancy of non-small cell lung cancer (NSCLC is largely due to its fast growth and invasion. WNT/β-catenin signaling plays a critical role in regulating NSCLC carcinogenesis. Hence, suppression of β-catenin signal transduction in NSCLC cells may improve the therapeutic outcome. Methods: We analyzed the levels of β-catenin and miR-3619-5p in NSCLC specimens, compared to paired non-tumor normal lung tissue (NT. We did Bioinformatics analyses on the binding sites of 3'-UTR of β-catenin mRNA by miR-3619-5p. We modified the levels of miR-3619-5p in NSCLC cells and examined their effects on β-catenin levels, and on the growth and invasion of NSCLC cells in an MTT assay and a transwell cell migration assay, respectively. Results: NSCLC specimens had significant higher levels of β-catenin, and significantly lower levels of miR-3619-5p, compared to NT. The levels of β-catenin and miR-3619-5p were inversely correlated in NSCLC specimens. Bioinformatics analyses showed that miR-3619-5p bound to 3'-UTR of β-catenin mRNA in NSCLC cells to inhibit its translation. Overexpression of miR-3619-5p decreased β-catenin protein, while depletion of miR-3619-5p increased β-catenin protein in NSCLC cells, without altering β-catenin mRNA levels. Overexpression of miR-3619-5p in NSCLC cells inhibited cell growth and invasion, while depletion of miR-3619-5p in NSCLC lines increased cell growth and invasion. Conclusion: Our data demonstrate a previously unappreciated role for miR-3619-5p in suppression of β-catenin-mediated cancer growth and invasion in NSCLC cells, and highlight miR-3619-5p as a novel cancer suppressor in NSCLC.

  14. Inhibitors of PI(4,5)P2 synthesis reveal dynamic regulation of IgE receptor signaling by phosphoinositides in RBL mast cells.

    Science.gov (United States)

    Santos, Marcela de Souza; Naal, Rose Mary Zumstein Georgetto; Baird, Barbara; Holowka, David

    2013-04-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a versatile phospholipid that participates in many membrane-associated signaling processes. PI(4,5)P2 production at the plasma membrane (PM) depends on levels of its precursor, phosphatidylinositol 4-phosphate (PI4P), synthesized principally by two intracellular enzymes, PI4-kinases IIIα and IIIb; the former is preferentially inhibited by phenylarsine oxide (PAO). We found that PAO and quercetin, another lipid kinase inhibitor, rapidly inhibit Ca(2+) responses to antigen in IgE-sensitized rat basophilic leukemia mast cells. Quercetin also rapidly inhibits store-operated Ca(2+) influx stimulated by thapsigargin. In addition, quercetin and PAO effectively inhibit antigen-stimulated ruffling and spreading in these cells, and they inhibit endocytosis of crosslinked IgE receptor complexes, evidently by inhibiting pinching off of endocytic vesicles containing the clustered IgE receptors. A minimal model to account for these diverse effects is inhibition of PI(4,5)P2 synthesis by PAO and quercetin. To characterize the direct effects of these agents on PI(4,5)P2 synthesis, we monitored the reappearance of the PI(4,5)P2-specific PH domain PH-phospholipase C δ-EGFP at the PM after Ca(2+) ionophore (A23187)-induced PI(4,5)P2 hydrolysis, followed by Ca(2+) chelation with excess EGTA. Resynthesized PI(4,5)P2 initially appears as micron-sized patches near the PM. Addition of quercetin subsequent to A23187-induced PI(4,5)P2 hydrolysis reduces PI(4,5)P2 resynthesis in PM-associated patches, and PAO reduces PI(4,5)P2 at the PM while enhancing PI(4,5)P2 accumulation at the Golgi complex. Taken together, these results provide evidence that PI4P generated by PI4-kinase IIIα is dynamically coupled to PI(4,5)P2 pools at the PM that are important for downstream signaling processes activated by IgE receptors.

  15. MiR-181b-5p downregulates NOVA1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma.

    Directory of Open Access Journals (Sweden)

    Feng Zhi

    Full Text Available MicroRNAs (miRNAs are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1 gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma.

  16. MiR-181b-5p downregulates NOVA1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma.

    Science.gov (United States)

    Zhi, Feng; Wang, Qiang; Deng, Danni; Shao, Naiyuan; Wang, Rong; Xue, Lian; Wang, Suinuan; Xia, Xiwei; Yang, Yilin

    2014-01-01

    MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma.

  17. Energy Efficiency Governance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    The purpose of this report is to help EE practitioners, government officials and stakeholders to establish the most effective EE governance structures, given their specific country context. It also aims to provide readers with relevant and accessible information to support the development of comprehensive and effective governance mechanisms. The International Energy Agency (IEA) conducted a global review of many elements of EE governance,including legal frameworks, institutional frameworks, funding mechanisms, co-ordination mechanisms and accountability arrangements, such as evaluation and oversight. The research tools included a survey of over 500 EE experts in 110 countries, follow-up interviews of over 120 experts in 27 countries and extensive desk study and literature searches on good EE governance.

  18. A new corporate governance

    Directory of Open Access Journals (Sweden)

    Ion Bucur

    2015-12-01

    Full Text Available The issue of corporate governance has become increasingly important as globalisation has begun to accelerate and the economic and financial turmoil have intensified. Post-crisis context has imposed the need to expand the prospects for analysis over governance and companies, as well as the need to identify new ways of administration and resource management. From this perspective, the author aims to highlight the conditions, factors and events that have generated profound changes within the business environment, while the analysis is focusing on contemporary changes in the systems of corporate governance and economic mutations, especially in terms of the companies. The establishment of new governance rules is demanding a theoretical approach based on new methodological requirements which are needed to reform theoretical foundations and to promote creative and effective shapes and governance systems.

  19. Privacy and Open Government

    Directory of Open Access Journals (Sweden)

    Teresa Scassa

    2014-06-01

    Full Text Available The public-oriented goals of the open government movement promise increased transparency and accountability of governments, enhanced citizen engagement and participation, improved service delivery, economic development and the stimulation of innovation. In part, these goals are to be achieved by making more and more government information public in reusable formats and under open licences. This paper identifies three broad privacy challenges raised by open government. The first is how to balance privacy with transparency and accountability in the context of “public” personal information. The second challenge flows from the disruption of traditional approaches to privacy based on a collapse of the distinctions between public and private sector actors. The third challenge is that of the potential for open government data—even if anonymized—to contribute to the big data environment in which citizens and their activities are increasingly monitored and profiled.

  20. THEORIES OF CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Sorin Nicolae BORLEA

    2013-03-01

    Full Text Available This study attempts to provide a theoretical framework for the corporate governance debate. The review of various corporate governance theories enhances the major objective of corporate governance which is maximizing the value for shareholders by ensuring good social and environment performances. The theories of corporate governance are rooted in agency theory with the theory of moral hazard’s implications, further developing within stewardship theory and stakeholder theory and evolving at resource dependence theory, transaction cost theory and political theory. Later, to these theories was added ethics theory, information asymmetry theory or the theory of efficient markets. These theories are defined based on the causes and effects of variables such as: the configuration of the board of directors, audit committee, independence of managers, the role of top management and their social relations beyond the legal regulatory framework. Effective corporate governance requires applying a combination

  1. Governance of the future

    DEFF Research Database (Denmark)

    Galløe, Lotte Rannveig

    In my presentation I will explore the concept, ‘technology of the future’, in public governance. Public governance within social services aims at changing the existing conditions for the marginalized citizens including children with special needs. I pose the question: what happens if public...... governance seek to chance the possible future conditions and targets the marginalized child’s relatives? Parent Management Training (PMTO) is studied as a technology of the future that expands and transforms governance. PMTO targets parents with aggressive and asocial children and aims to “create the parent...... as the child’s best teacher”. The program involves parents as facilitators modifying the child’s behavior instead of working directly on the child, thereby widening the target of intervention. PMTO exemplifies an arrangement that engages the private sphere in the conduct of public governance aiming at creating...

  2. 《榆林日报》时政新闻中的政府媒介形象塑造与改进策略%The Government Media Images’Shaping and Strategies of Improvement in the Political News’Coverage on Yulin Daily

    Institute of Scientific and Technical Information of China (English)

    苏晓暹; 熊秋萍

    2016-01-01

    新闻媒体对政府媒介形象的塑造通过多种方式来实现,时政新闻因其特殊的政治性、权威性和规范性成为建构政府媒介形象的最佳选择。在塑造地方政府媒介形象的过程中,《榆林日报》时政新闻采取了多种策略,其新闻文本在写作上表现出高度的规范性,题材和视角上具有较强的民生化倾向,有利于塑造良好的榆林市政府媒介形象。从塑造政府媒介形象的角度出发,《榆林日报》还需在现有基础上作出改进。%News media shapes the government media image through a variety of ways. There are many special char-acteristics in the coverage of political news,such as political nature,authority and normalization,which makes it the best choice to construct the government media image. In the course of shaping the government media image, Yulin Daily has adopted a variety of strategies. The political news in this newspaper is written normatively and standardly. Its theme and viewpoint choice has a strong tendency to people’s livelihood. Those approaches help improve the Yulin government media image shaping. Some corresponding suggestions on their improvement are put forward ,which can become a reference for Yulin Daily to improve its credibility and preferably shape the Yulin gov-ernment media image.

  3. Information Management and Governance in UK Higher Education Institutions: Bringing IT in from the Cold

    Science.gov (United States)

    Coen, Michael; Kelly, Ursula

    2007-01-01

    In the 21st Century, IT Governance is, within the broader corporate governance context, critical for all organisations. Those without an IT governance strategy face significant risks; those with one perform measurably better (Calder 2005). There has been little field based research on IT governance, and few publications help managers understand…

  4. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

    DEFF Research Database (Denmark)

    Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah;

    2013-01-01

    improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc...... and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where...

  5. Hsa-miR-590-5p Interaction with SMAD3 Transcript Supports Its Regulatory Effect on The TGFβ Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Meisam Jafarzadeh

    2016-04-01

    Full Text Available Objective: SMAD proteins are the core players of the transforming growth factor-beta (TGFβ signaling pathway, a pathway which is involved in cell proliferation, differentiation and migration. On the other hand, hsa-miRNA-590-5p (miR-590-5p is known to have a negative regulatory effect on TGFβ signaling pathway receptors. Since, RNAhybrid analysis suggested SMAD3 as a bona fide target gene for miR-590, we intended to investigate the effect of miR-590-5p on SMAD3 transcription. Materials and Methods: In this experimental study, miR-590-5p was overexpressed in different cell lines and its increased expression was detected through quantitative reverse transcription-polymerase chain reaction (RT-qPCR. Western blot analysis was then used to investigate the effect of miR-590-5p overexpression on SMAD3 protein level. Next, the direct interaction of miR-590-5p with the 3´-UTR sequence of SMAD3 transcript was investigated using the dual luciferase assay. Finally, flow cytometery was used to investigate the effect of miR-590-5p overexpression on cell cycle progression in HeLa and SW480 cell lines. Results: miR-590-5p was overexpressed in the SW480 cell line and its overexpression resulted in significant reduction of the SMAD3 protein level. Consistently, direct interaction of miR-590-5p with 3´-UTR sequence of SMAD3 was detected. Finally, miR-590-5p overexpression did not show a significant effect on cell cycle progression of Hela and SW480 cell lines. Conclusion: Consistent with previous reports about the negative regulatory effect of miR-590 on TGFβ receptors, our data suggest that miR-590-5p also attenuates the TGFβ signaling pathway through down-regulation of SMAD3.

  6. Risk Management in IT Governance Framework

    Directory of Open Access Journals (Sweden)

    Mirela GHEORGHE

    2011-12-01

    Full Text Available The concept of governance has an already old contour: the system by which business corporations are directed and controlled. The most praised principles regarding shareholder rights, transparency and board accountability now constitute the foundation for new tendencies evolved from such ground. Executive compensation, transparency and shareholder reporting are new issues attached to board responsibilities. Besides such almost negative approaches the board faces a more and more prominent role from risk management and IT governance perspective. Nowadays is generally acknowledged that the board is in charge for managing and controlling the risks to assets of the enterprises and business future. IT Governance has emerged as a support for corporate governance, as an important part of board’s striving efforts to perform better in a competition environment. These responsibilities, risk management and IT Governance, remain within the framework of old concept of corporate governance and are fed from its substance. The interaction between these concepts is the core interest of this research.IT Governance is defined as procedures and policies established in order to assure that the IT system of an organization sustains its goals and strategies. The management of the organisations face a new challenge: structural redefinition of the IT component in order to create plus value and to minimize IT risks through an efficient management of all IT resources of the organisation. The evolution of the present IT environment is a natural process according to which business environment should adapt.

  7. Long non-coding RNA HOTAIR inhibits miR-17-5p to regulate osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head

    Science.gov (United States)

    Zhao, Baoxiang; Guo, Xiaxia; Liu, Song

    2017-01-01

    Background and aim The biological functions of non-coding RNAs (ncRNAs) have been widely identified in many human diseases. In the present study, the relationship between long non-coding RNA HOTAIR and microRNA-17-5p (miR-17-5p) and their roles in osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head (ONFH) were investigated. Methods The expression levels of HOTAIR and miR-17-5p in the mesenchymal stem cells (MSCs) derived from patients with non-traumatic ONFH and osteoarthritis (OA) were examined by real-time PCR. BMP-2 induced human MSCs from bone marrow (hMSC-BM) were used for osteogenic differentiation. Results It was observed that the expression level of miR-17-5p was lower and the level of HOTAIR was higher in samples of non-traumatic ONFH compared with OA. HOTAIR downregulation induced by si-HOTAIR led to the increase of miR-17-5p expression and the decrease of miR-17-5p target gene SMAD7 expression. The values of osteogenic differentiation markers, including RUNX2 and COL1A1 mRNA expression and ALP activity, were also elevated by si-HOTAIR. However, the increase of these values was canceled by miR-17-5p inhibitor or SMAD7 upregulation. Conclusion HOTAIR played a role in regulating osteogenic differentiation and proliferation through modulating miR-17-5p and its target gene SMAD7 in non-traumatic ONFH. PMID:28207735

  8. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China); Xia, Qiang, E-mail: xiaqiang1@yahoo.com.cn [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  9. Increased Expression of microRNA-199b-5p Associates with Poor Prognosis Through Promoting Cell Proliferation, Invasion and Migration Abilities of Human Osteosarcoma.

    Science.gov (United States)

    Zeng, Haibin; Zhang, Zhong; Dai, Xiaoming; Chen, Yongzhong; Ye, Jianhua; Jin, Zhixin

    2016-04-01

    MicroRNA (miR)-199b-5p has been reported to be upregulated in human osteosarcoma tissues and participate in the Notch signaling in osteosarcoma cells. This study was aimed to investigate the associations of miR-199b-5p expression with tumor progression of primary osteosarcoma, and to deepen the understanding of its involvement in carcinogenesis. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect expression levels of miR-199b-5p in 98 osteosarcoma and corresponding adjacent normal tissues. Then, the correlations of its expression with clinicopathological characteristics and patient prognosis were statistically analyzed. Moreover, in vitro assays were performed to assess the effects of miR-199b-5p on the proliferation, migration and invasion of two human osteosarcoma cell lines MG63 and U2OS. Compared to normal controls, miR-199b-5p expression was significantly upregulated in osteosarcoma tissues (P osteosarcoma patients with high tumor grade (P = 0.008), positive metastasis (P = 0.001) and positive recurrence (P = 0.001) were markedly higher than those with low tumor grade, negative metastasis and negative recurrence. Moreover, osteosarcoma patients with high miR-199b-5p expression showed shorter overall survival (P osteosarcoma cells. This study offer the convincing evidence for the first time that the increased expression of miR-199b-5p may play crucial roles in aggressive progression and poor prognosis of human osteosarcoma. miR-199b-5p may function as an oncogene by positively regulating the malignant potentials of this neoplasm.

  10. MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma

    Science.gov (United States)

    Wang, Chen; Ba, Ximing; Guo, Yu; Sun, Defang; Jiang, Haoyang; Li, Wentao; Huang, Zhen; Zhou, Guangxin; Wu, Sujia; Zhang, Junfeng; Chen, Jiangning

    2017-01-01

    Osteosarcoma (OS) is the most common primary bone malignancy and remains a leading cause of cancer-related deaths in adolescents. Emerging evidence indicates that microRNAs (miRNAs) are correlated with clinical and biological characteristics of OS. However, the involvement of miR-199a-5p in OS development remains unclear. In this study, we examined the function of miR-199a-5p in vitro and in vivo. The results showed that miR-199a-5p was significantly up-regulated in OS patient tissues and cells. The inhibition of miR-199a-5p led to a significant decrease in cell proliferation and tumour growth. We further demonstrated that miR-199a-5p could directly bind to the 3′UTRs of the mRNA of both PIAS3 and p27 and mediate a decrease in the protein levels of PIAS3 and p27, thereby stimulating STAT3 activation and cell cycle progression in OS cells. Rescue experiments of PIAS3 and p27 further revealed that PIAS3 and p27 were functional targets of miR-199a-5p. Moreover, enhancing the expressions of both PIAS3 and p27 using miR-199a-5p-targeted inhibitors in an OS xenograft model was shown to be a promising approach for OS clinical therapy. Our findings indicate that the pathway of miR-199a-5p targeting both PIAS3 and p27 is a possible mechanism that contributes to tumour growth in OS. PMID:28120918

  11. Distinct Roles of PI(3,4,5)P3 during Chemoattractant Signaling in Dictyostelium : A Quantitative In Vivo Analysis by Inhibition of PI3-Kinase

    NARCIS (Netherlands)

    Loovers, Harriet; Postma, Marten; Keizer-Gunnink, Ineke; Huang, Yi Elaine; Devreotes, Peter N.; Haastert, Peter J.M. van

    2006-01-01

    The role of PI(3,4,5)P3 in Dictyostelium signal transduction and chemotaxis was investigated using the PI3-kinase inhibitor LY294002 and pi3k-null cells. The increase of PI(3,4,5)P3 levels after stimulation with the chemoattractant cAMP was blocked >95% by 60 µM LY294002 with half-maximal effect at

  12. PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer.

    Science.gov (United States)

    Song, Wei; Tang, Lin; Xu, Yumei; Xu, Jing; Zhang, Wenwen; Xie, Hui; Wang, Shui; Guan, Xiaoxiang

    2017-02-08

    Emerging evidence has shown that adding poly(ADP-ribose) polymerase (PARP) inhibitors to chemotherapy regimens is superior to the control regimens alone in BRCA1-mutated triple-negative breast cancer (TNBC) patients, but their underlying mechanisms have not been fully elucidated. In this study, using miRNA microarray analysis of two BRCA1-mutated TNBC cell lines, we found that miR-664b-5p expression was increased after adding a PARP inhibitor, olaparib, to a carboplatin (CBP) plus gemcitabine (GEM) therapy regimen. Functional assays showed miR-664b-5p overexpression inhibited proliferation, migration and invasion in BRCA1-mutated TNBC cells. CCNE2 was identified as a novel functional target of miR-664b-5p, and CCNE2 knockdown revealed effects similar to those observed with miR-664b-5p overexpression. Both CCNE2 knockdown and miR-664b-5p overexpression significantly increased the chemosensitivity of BRCA1-mutated TNBC cells. In addition, in vivo studies indicated that miR-664b-5p inhibited tumour growth compared with the control in tumour xenograft models, and we also found that CCNE2 expression was inversely correlated with miR-664b-5p expression in 90 TNBC patient samples. In conclusion, miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC.

  13. PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer

    Science.gov (United States)

    Song, Wei; Tang, Lin; Xu, Yumei; Xu, Jing; Zhang, Wenwen; Xie, Hui; Wang, Shui; Guan, Xiaoxiang

    2017-01-01

    Emerging evidence has shown that adding poly(ADP-ribose) polymerase (PARP) inhibitors to chemotherapy regimens is superior to the control regimens alone in BRCA1-mutated triple-negative breast cancer (TNBC) patients, but their underlying mechanisms have not been fully elucidated. In this study, using miRNA microarray analysis of two BRCA1-mutated TNBC cell lines, we found that miR-664b-5p expression was increased after adding a PARP inhibitor, olaparib, to a carboplatin (CBP) plus gemcitabine (GEM) therapy regimen. Functional assays showed miR-664b-5p overexpression inhibited proliferation, migration and invasion in BRCA1-mutated TNBC cells. CCNE2 was identified as a novel functional target of miR-664b-5p, and CCNE2 knockdown revealed effects similar to those observed with miR-664b-5p overexpression. Both CCNE2 knockdown and miR-664b-5p overexpression significantly increased the chemosensitivity of BRCA1-mutated TNBC cells. In addition, in vivo studies indicated that miR-664b-5p inhibited tumour growth compared with the control in tumour xenograft models, and we also found that CCNE2 expression was inversely correlated with miR-664b-5p expression in 90 TNBC patient samples. In conclusion, miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC. PMID:28176879

  14. Institutionalizing Global Governance

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich

    2012-01-01

    The United Nations Global Compact – which is a Global Public Policy Network advocating 10 universal principles in the areas of human rights, labor standards, environmental protection, and anticorruption – has turned into the world's largest corporate responsibility initiative. Although the Global...... Compact is often characterized as a promising way to address global governance gaps, it remains largely unclear why this is the case. To address this problem, we discuss to what extent the initiative represents an institutional solution to exercise global governance. We suggest that new governance modes...

  15. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Valentina Manfè

    Full Text Available Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4.

  16. Identification of Toxoplasma TgPH1, a pleckstrin homology domain-containing protein that binds to the phosphoinositide PI(3,5)P2.

    Science.gov (United States)

    Daher, Wassim; Morlon-Guyot, Juliette; Alayi, Tchilabalo Dilezitoko; Tomavo, Stan; Wengelnik, Kai; Lebrun, Maryse

    2016-05-01

    The phosphoinositide phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) plays crucial roles in the maintenance of lysosome/vacuole morphology, membrane trafficking and regulation of endolysosome-localized membrane channel activity. In Toxoplasma gondii, we previously reported that PI(3,5)P2 is essential for parasite survival by controlling homeostasis of the apicoplast, a particular organelle of algal origin. Here, by using a phosphoinositide pull-down assay, we identified TgPH1 in Toxoplasma a protein conserved in many apicomplexan parasites. TgPH1 binds specifically to PI(3,5)P2, shows punctate intracellular localization, but plays no vital role for tachyzoite growth in vitro. TgPH1 is a protein predominantly formed by a pleckstrin homology (PH) domain. So far, PH domains have been described to bind preferentially to bis- or trisphosphate phosphoinositides containing two adjacent phosphates (i.e. PI(3,4)P2, PI(4,5)P2, PI(3,4,5)P3). Therefore, our study reveals an unusual feature of TgPH1 which binds preferentially to PI(3,5)P2.

  17. Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2].

    Science.gov (United States)

    Kolay, Sourav; Basu, Urbashi; Raghu, Padinjat

    2016-06-15

    Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a multi-functional lipid that regulates several essential subcellular processes in eukaryotic cells. In addition to its well-established function as a substrate for receptor-activated signalling at the plasma membrane (PM), it is now recognized that distinct PI(4,5)P2 pools are present at other organelle membranes. However, a long-standing question that remains unresolved is the mechanism by which a single lipid species, with an invariant functional head group, delivers numerous functions without loss of fidelity. In the present review, we summarize studies that have examined the molecular processes that shape the repertoire of PI(4,5)P2 pools in diverse eukaryotes. Collectively, these studies indicate a conserved role for lipid kinase isoforms in generating functionally distinct pools of PI(4,5)P2 in diverse metazoan species. The sophistication underlying the regulation of multiple functions by PI(4,5)P2 is also shaped by mechanisms that regulate its availability to enzymes involved in its metabolism as well as molecular processes that control its diffusion at nanoscales in the PM. Collectively, these mechanisms ensure the specificity of PI(4,5)P2 mediated signalling at eukaryotic membranes.

  18. Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells.

    Science.gov (United States)

    Guan, Hongbing; Singh, Udai P; Rao, Roshni; Mrelashvili, Davit; Sen, Souvik; Hao, Haiping; Zumbrun, Elizabeth E; Singh, Narendra P; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-04-01

    The role of microRNA in the regulation of encephalitogenic T-cell development is of interest in understanding the pathogenesis of multiple sclerosis (MS). Direct binding of microRNAs to their target mRNAs usually suppresses gene expression and facilitates mRNA degradation. In this study, we observed that the expression of several microRNAs was significantly altered in patients with MS. Interestingly, the expression of miR-140-5p, among other microRNAs, was significantly decreased in the peripheral blood mononuclear cells of patients with MS, and this microRNA may regulate encephalitogenic T helper type 1 (Th1) cell differentiation. The expression level of miR-140-5p was inversely correlated with disease severity with greater reduction in relapsing disease compared with remitting disease. Transfection of synthetic miR-140-5p in peripheral blood mononuclear cells suppressed encephalitogenic Th1 differentiation. Signal transducer and activator of transcription 1 (STAT1) was the functional target of miR-140-5p - transfection of the synthetic miR-140-5p suppressed activation of STAT1 and the expression of its downstream target, T-bet. Our results suggested that miR-140-5p is probably involved in the regulation of encephalitogenic T cells in the pathogenesis of MS.

  19. PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome.

    Science.gov (United States)

    Dong, Xian-ping; Shen, Dongbiao; Wang, Xiang; Dawson, Taylor; Li, Xinran; Zhang, Qi; Cheng, Xiping; Zhang, Yanling; Weisman, Lois S; Delling, Markus; Xu, Haoxing

    2010-07-13

    Membrane fusion and fission events in intracellular trafficking are controlled by both intraluminal Ca(2+) release and phosphoinositide (PIP) signalling. However, the molecular identities of the Ca(2+) release channels and the target proteins of PIPs are elusive. In this paper, by direct patch-clamping of the endolysosomal membrane, we report that PI(3,5)P(2), an endolysosome-specific PIP, binds and activates endolysosome-localized mucolipin transient receptor potential (TRPML) channels with specificity and potency. Both PI(3,5)P(2)-deficient cells and cells that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking defects in the late endocytic pathway. We find that the enlarged vacuole phenotype observed in PI(3,5)P(2)-deficient mouse fibroblasts is suppressed by overexpression of TRPML1. Notably, this PI(3,5)P(2)-dependent regulation of TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces Ca(2+) release from the vacuole. In this study, we show that this release requires both PI(3,5)P(2) production and a yeast functional TRPML homologue. We propose that TRPMLs regulate membrane trafficking by transducing information regarding PI(3,5)P(2) levels into changes in juxtaorganellar Ca(2+), thereby triggering membrane fusion/fission events.

  20. Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): inhibition of bladder cancer cell aggressiveness

    Science.gov (United States)

    Matsushita, Ryosuke; Yoshino, Hirofumi; Enokida, Hideki; Goto, Yusuke; Miyamoto, Kazutaka; Yonemori, Masaya; Inoguchi, Satoru; Nakagawa, Masayuki; Seki, Naohiko

    2016-01-01

    In microRNA (miRNA) biogenesis, the guide-strand of miRNA integrates into the RNA induced silencing complex (RISC), whereas the passenger-strand is inactivated through degradation. Analysis of our miRNA expression signature of bladder cancer (BC) by deep-sequencing revealed that microRNA (miR)-145-5p (guide-strand) and miR-145-3p (passenger-strand) were significantly downregulated in BC tissues. It is well known that miR-145-5p functions as a tumor suppressor in several types of cancer. However, the impact of miR-145-3p on cancer cells is still ambiguous. The aim of the present study was to investigate the functional significance of miR-145-3p and BC oncogenic pathways and targets regulated by miR-145-5p/miR-145-3p. Ectopic expression of either miR-145-5p or miR-145-3p in BC cells significantly suppressed cancer cell growth, migration and invasion and it also induced apoptosis. The gene encoding ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was a direct target of these miRNAs. Silencing of UHRF1 induced apoptosis and inhibited cancer cell proliferation, migration, and invasion in BC cells. In addition, overexpressed UHRF1 was confirmed in BC clinical specimens, and the high UHRF1 expression group showed a significantly poorer cause specific survival rate in comparison with the low expression group. Taken together, our present data demonstrated that both strands of miR-145 (miR-145-5p: guide-strand and miR-145-3p: passenger-strand) play pivotal roles in BC cells by regulating UHRF1. The identification of the molecular target of a tumor suppressive miRNAs provides novel insights into the potential mechanisms of BC oncogenesis and suggests novel therapeutic strategies. PMID:27072587

  1. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  2. Transnational Governance and Constitutionalism

    DEFF Research Database (Denmark)

    Joerges, Christian; Sand, Inger-Johanne; Teubner, Gunther

    The term transnational governance designates untraditional types of international and regional collaboration among both public and private actors. These legally-structured or less formal arrangements link economic, scientific and technological spheres with political and legal processes. They are ...

  3. Global Governance of Migration

    OpenAIRE

    2011-01-01

    The aim of this thesis is to analyze the recently formed global governance of migration, which has got an unprecedented trans-boundary nature due to the impacts og globalization in the post Cold War era. 

  4. Government Risk-Bearing

    CERN Document Server

    1993-01-01

    The u.s. government bulks large in the nation's financial markets. The huge volume of government-issued and -sponsored debt affects the pricing and volume ofprivate debt and, consequently, resource allocation between competing alternatives. What is often not fully appreciated is the substantial influence the federal government wields overresource allocation through its provisionofcreditandrisk-bearing services to the private economy. Because peopleand firms generally seekto avoid risk, atsomeprice they are willing to pay another party to assume the risk they would otherwise face. Insurance companies are a class of private-sector firms one commonly thinks of as providing these services. As the federal government has expanded its presence in the U.S. economy during this century, it has increasingly developed programs aimed at bearing risks that the private sector either would not take on at any price, or would take on but atapricethoughtto besogreatthatmostpotentialbeneficiarieswouldnotpurchase the coverage. To...

  5. Codes of Good Governance

    DEFF Research Database (Denmark)

    Beck Jørgensen, Torben; Sørensen, Ditte-Lene

    2013-01-01

    Good governance is a broad concept used by many international organizations to spell out how states or countries should be governed. Definitions vary, but there is a clear core of common public values, such as transparency, accountability, effectiveness, and the rule of law. It is quite likely......, however, that national views of good governance reflect different political cultures and institutional heritages. Fourteen national codes of conduct are analyzed. The findings suggest that public values converge and that they match model codes from the United Nations and the European Council as well...... as conceptions of good governance from other international organizations. While values converge, they are balanced and communicated differently, and seem to some extent to be translated into the national cultures. The set of global public values derived from this analysis include public interest, regime dignity...

  6. Motorvejen, byudviklingen og governance

    DEFF Research Database (Denmark)

    Hansen, Carsten Jahn; Nielsen, Thomas Alexander Sick; Harder, Henrik

    2006-01-01

    mere netværksprægede, dialog-orienterede, fleksible og tværgående. Denne forandring er i samfundsvidenskaben blevet karakteriseret som en bevægelse fra government til governance. Med udgangspunkt i forskningsprojektet Byen, Vejen og Landskabet (BVL) har dette paper til hensigt at diskutere karakteren...... indblik i den påstående bevægelse eller forandring i styreformer fra government til governance. Dernæst dokumenteres og beskrives nogle af de overvejelser, der har ligget til grund for de byudviklingstendenser, der har fundet sted indtil nu i det østjyske bybånd. Dette sker konkret med afsæt i...

  7. Suing the Government

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ordinary people getting involved in administrative lawsuits usually find themselves under great pressure, as they doubt whether their cases can be treated impartially Slapping local government with a lawsuit isn’t something you imme-diately equate with o

  8. Making Government Work Better

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The reform of China’s government bodies got a powerful push this March as lawmakers at the National People’s Congress approved an extensive reshuffle plan of the State Council,which focuses on streamlining government department functions.In a recent interview with People’s Daily and Xinhua News Agency,a spokesperson for the State Commission Office for Public Sector Reform answered questions about the progress being made in the administrative reform.

  9. Minsky on "Big Government"

    Directory of Open Access Journals (Sweden)

    Daniel de Santana Vasconcelos

    2014-03-01

    Full Text Available This paper objective is to assess, in light of the main works of Minsky, his view and analysis of what he called the "Big Government" as that huge institution which, in parallels with the "Big Bank" was capable of ensuring stability in the capitalist system and regulate its inherently unstable financial system in mid-20th century. In this work, we analyze how Minsky proposes an active role for the government in a complex economic system flawed by financial instability.

  10. Government information transparency

    OpenAIRE

    Esteban, Joan; Albornoz, Facundo; Vanin, Paolo

    2009-01-01

    This paper studies a model of announcements by a privately informed government about the future state of the economic activity in an economy subject to recurrent shocks and with distortions due to income taxation. Although transparent communication would ex ante be desirable, we find that even a benevolent government may ex-post be non-informative, in an attempt to countervail the tax distortion with a 'second best' compensating distortion in information. This result provides a rationale for ...

  11. Risk governance in agriculture

    OpenAIRE

    Bachev, Hrabrin

    2008-01-01

    This paper identifies and assesses the efficiency of major modes for risk governance in agriculture on the base of Bulgarian dairy farming. Firstly, the New Institutional and Transaction Costs Economics is incorporated and a framework for analysis of the governance of natural, market, private, and social (institutional) risks presented. Next, the pace and challenges of the dairy farming development during the post-communist transition and EU integration is outlined. Third, major types of risk...

  12. Governing Global Migration

    OpenAIRE

    2008-01-01

    This study explores the global regulative function of migration politics. Its main aim is to rethink migration politics through an engagement with the Foucauldian governmentality perspective, which focuses on the relation between government and thought. A secondary aim is to use this perspective to explore the global description of migration and migration politics which is emerging with the currently evolving global governance of migration. Doing so, it wishes to contribute both to the study ...

  13. Global Ocean Governance

    OpenAIRE

    Dorota Pyc

    2016-01-01

    This paper presents a few general comments on the effective global ocean governance (GOG). The Convention on the Law of the Sea (UNCLOS) establishes fundamental legal principles for the governance of the marine environment and its resources. Furthermore, in the context of GOG the international community is conscious that improving of global and regional cooperation ought to be in the mainstream of socio-economic and political discourse. Nowadays, the UNCLOS is not able to give an answer for a...

  14. 公共图书馆政府决策参考咨询服务模块化设计策略--以长春图书馆为例%The Modular Design Strategy for Public Library ’s Reference Service for Government Decision-making---Taking Changchun Library as an Example

    Institute of Scientific and Technical Information of China (English)

    张昭

    2014-01-01

    阐述了公共图书馆政府决策参考咨询服务模块化设计的必要性、原则及组织方式,从主体设计和固定模块设计两方面探讨了图书馆决策参考专刊服务的模块化设计,介绍了长春图书馆政府决策信息服务模块化设计的实践。%This paper expounds the importance, principles and organization modes of the modular design strategy for public library’s reference service for government decision-making, and from two aspects of the main body design and the fixed module design, probes into the modular design of library’s special service for government decision-making, and introduces the practice of Changchun Library in the modular design of its reference service for government decision-making.

  15. E-Government Implementation

    Directory of Open Access Journals (Sweden)

    Solinthone Phonepaseuth

    2016-01-01

    Full Text Available Information and communication technologies (ICTs are playing an increasingly vital role in the daily lives of people, revolutionizing work and leisure and changing the rules of doing business. In the realm of government, ICT applications are promising to enhance the delivery of public goods and services to citizens not only by improving the process and management of government, but also by redefining the traditional concepts of citizenship and democracy. The ICTs’ effect on societies are both far-reaching and uneven. On the one hand, ICT is fueling the transition from industrial-based economies to knowledge-based societies. On the other hand, ICT still has little or no impact in the lives of people in many countries. This wide disparity in the impact of ICT around the world today underscores the uneven progress of economic development. It also highlights the critical role of government in the information age. The goal of this article is to provide a brief overview of E-government studies and their evaluation, to clarify the major issues, which can make E-government to be more effective, transparent and responsive. The article considers the significance of contemporary E-government activity.

  16. miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK.

    Directory of Open Access Journals (Sweden)

    Feng Zhi

    Full Text Available Astrocytomas are common malignant intracranial tumors that comprise the majority of adult primary central nervous system tumors. MicroRNAs (miRNAs are small, non-coding RNAs (20-24 nucleotides that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In our previous studies, we found that the downregulation of miR-106a-5p in astrocytomas is associated with poor prognosis. However, its specific gene target(s and underlying functional mechanism(s in astrocytomas remain unclear. In this study, we used mRNA microarray experiments to measure global mRNA expression in the presence of increased or decreased miR-106a-5p levels. We then performed bioinformatics analysis based on multiple target prediction algorithms to obtain candidate target genes that were further validated by computational predictions, western blot analysis, quantitative real-time PCR, and the luciferase reporter assay. Fas-activated serine/threonine kinase (FASTK was identified as a direct target of miR-106a-5p. In human astrocytomas, miR-106a-5p is downregulated and negatively associated with clinical staging, whereas FASTK is upregulated and positively associated with advanced clinical stages, at both the protein and mRNA levels. Furthermore, Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the increased expression of FASTK is significantly associated with poor survival outcome. These results further supported the finding that FASTK is a direct target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and FASTK during astrocytoma progression. Through gain-of-function and loss-of-function studies, we demonstrated that miR-106a-5p can significantly inhibit cell proliferation and migration and can promote cell apoptosis in vitro. The knockdown of FASTK induced similar effects on astrocytoma cells as those induced by the overexpression of miR-106a-5p. These

  17. n-3 polyunsaturated fatty acids suppress CD4(+) T cell proliferation by altering phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] organization.

    Science.gov (United States)

    Hou, Tim Y; Barhoumi, Rola; Fan, Yang-Yi; Rivera, Gonzalo M; Hannoush, Rami N; McMurray, David N; Chapkin, Robert S

    2016-01-01

    The mechanisms by which n-3 polyunsaturated fatty acids (n-3 PUFA), abundant in fish oil, exert their anti-inflammatory effects have not been rigorously defined. We have previously demonstrated that n-3 PUFA decrease the amount of phosphatidylinositol-(4,5)-bisphosphate, [PI(4,5)P2], in CD4(+) T cells, leading to suppressed actin remodeling upon activation. Since discrete pools of PI(4,5)P2 exist in the plasma membrane, we determined whether n-3 PUFA modulate spatial organization of PI(4,5)P2 relative to raft and non-raft domains. We used Förster resonance energy transfer (FRET) to demonstrate that lipid raft mesodomains in the plasma membrane of CD4(+) T cells enriched in n-3 PUFA display increased co-clustering of Lck(N10) and LAT(ΔCP), markers of lipid rafts. CD4(+) T cells enriched in n-3 PUFA also exhibited a depleted plasma membrane non-raft PI(4,5)P2 pool as detected by decreased co-clustering of Src(N15), a non-raft marker, and PH(PLC-δ), a PI(4,5)P2 reporter. Incubation with exogenous PI(4,5)P2 rescued the effects on the non-raft PI(4,5)P2 pool, and reversed the suppression of T cell proliferation in CD4(+) T cells enriched with n-3 PUFA. Furthermore, CD4(+) T cells isolated from mice fed a 4% docosahexaenoic acid (DHA)-enriched diet exhibited a decrease in the non-raft pool of PI(4,5)P2, and exogenous PI(4,5)P2 reversed the suppression of T cell proliferation. Finally, these effects were not due to changes to post-translational lipidation, since n-3 PUFA did not alter the palmitoylation status of signaling proteins. These data demonstrate that n-3 PUFA suppress T cell proliferation by altering plasma membrane topography and the spatial organization of PI(4,5)P2.

  18. Curcumin promotes apoptosis by activating the p53-miR-192-5p/215-XIAP pathway in non-small cell lung cancer.

    Science.gov (United States)

    Ye, Mingxiang; Zhang, Jin; Zhang, Jiän; Miao, Qing; Yao, Libo; Zhang, Jian

    2015-02-01

    Curcumin has attracted increasing interest as an anti-cancer drug for decades. The mechanisms of action involve multiple cancer-related signaling pathways. Recent studies highlighted curcumin has epigenetic regulatory effects on miRNA in cancers. In the present study, we demonstrated the proapoptotic effects of curcumin in vitro and in vivo. miRNA microarray and qPCR indicated that miR-192-5p and miR-215 were the most responsive miRNAs upon curcumin treatment in H460 and A427 cells. Functional studies showed miR-192-5p/215 were putative tumor suppressors in non-small cell lung cancer. Curcumin also promoted miR-192-5p/215 expressions in A549 cells (p53 wild type) but not in H1299 cells (p53-null). Conditional knockdown of p53 by tetracycline inducible expression system significantly abrogated curcumin-induced miR-192-5p/215 upregulation in the p53 wild-type H460, A427 and A549 cells. Conversely, ectopic expression of exogenous wild-type but not R273H mutant p53 in the p53-null H1299 cells enabled miR-192-5p/215 response to curcumin treatment. The proapoptotic effects of curcumin also depended on miR-192-5p/215 induction, and antagonizing miR-192-5p/215 expression attenuated curcumin-induced apoptosis in H460, A427 and A549 cells, but not in H1299 cells. Finally, X-linked inhibitor of apoptosis (XIAP) is proved to be a novel transcriptional target of miR-192-5p/215. Taken together, this study highlights that the proapoptotic effects of curcumin depend on miR-192-5p/215 induction and the p53-miR-192-5p/215-XIAP pathway is an important therapeutic target for non-small cell lung cancer.

  19. Ins(1,4,5)P3 interacts with PIP2 to regulate activation of TRPC6/C7 channels by diacylglycerol in native vascular myocytes.

    Science.gov (United States)

    Ju, Min; Shi, Jian; Saleh, Sohag N; Albert, Anthony P; Large, William A

    2010-05-01

    We investigated synergism between inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and diacylglycerol (DAG) on TRPC6-like channel activity in rabbit portal vein myocytes using single channel recording and immunoprecipitation techniques. Ins(1,4,5)P(3) at 10 microm increased 3-fold TRPC6-like activity induced by 10 microm 1-oleoyl-2-acetyl-sn-glycerol (OAG), a DAG analogue. Ins(1,4,5)P(3) had no effect on OAG-induced TRPC6 activity in mesenteric artery myocytes. Anti-TRPC6 and anti-TRPC7 antibodies blocked channel activity in portal vein but only anti-TRPC6 inhibited activity in mesenteric artery. TRPC6 and TRPC7 proteins strongly associated in portal vein but only weakly associated in mesenteric artery tissue lysates. Therefore in portal vein the conductance consists of TRPC6/C7 subunits, while OAG activates a homomeric TRPC6 channel in mesenteric artery myocytes. Wortmannin at 20 microm reduced phosphatidylinositol 4,5-bisphosphate (PIP(2)) association with TRPC6 and TRPC7, and produced a 40-fold increase in OAG-induced TRPC6/C7 activity. Anti-PIP(2) antibodies evoked TRPC6/C7 activity, which was blocked by U73122, a phospholipase C inhibitor. DiC8-PIP(2), a water-soluble PIP(2) analogue, inhibited OAG-induced TRPC6/C7 activity with an IC(50) of 0.74 microm. Ins(1,4,5)P(3) rescued OAG-induced TRPC6/C7 activity from inhibition by diC8-PIP(2) in portal vein myocytes, and this was not prevented by the Ins(1,4,5)P(3) receptor antagonist heparin. In contrast, Ins(1,4,5)P(3) did not overcome diC8-PIP(2)-induced inhibition of TRPC6 activity in mesenteric artery myocytes. 2,3,6-Tri-O-butyryl-Ins(1,4,5)P(3)/AM (6-Ins(1,4,5)P(3)), a cell-permeant analogue of Ins(1,4,5)P(3), at 10 microm increased TRPC6/C7 activity in portal vein and reduced association between TRPC7 and PIP(2), but not TRPC6 and PIP(2). In contrast, 10 microm OAG reduced association between TRPC6 and PIP(2), but not between TRPC7 and PIP(2). The present work provides the first evidence that Ins(1,4,5)P(3

  20. Open Government and (Linked (Open (Government (Data

    Directory of Open Access Journals (Sweden)

    Christian Philipp Geiger

    2012-12-01

    Full Text Available This article explores the opening and the free usage of stored public sector data, supplied by state. In the age of Open Government and Open Data it’s not enough just to put data online. It should be rather weighed out whether, how and which supplied public sector data can be published. Open Data are defined as stored data which could be made accessible in a public interest without any restrictions for usage and distribution. These Open Data can possibly be statistics, geo data, maps, plans, environmental data and weather data in addition to materials of the parliaments, ministries and authorities. The preparation and the free access to existing data permit varied approaches to the reuse of data, discussed in the article. In addition, impulses can be given for Open Government – the opening of state and administration, to more transparency, participation and collaboration as well as to innovation and business development. The Open Data movement tries to get to the bottom of current publication processes in the public sector which could be formed even more friendly to citizens and enterprises.

  1. Shared Governance and Regional Accreditation: Institutional Processes and Perceptions

    Science.gov (United States)

    McGrane, Wendy L.

    2013-01-01

    This qualitative single-case research study was conducted to gain deeper understanding of the institutional processes to address shared governance accreditation criteria and to determine whether institutional processes altered stakeholder perceptions of shared governance. The data collection strategies were archival records and personal…

  2. “半公众参与决策模式”应对邻避冲突的政府策略∗%“Semi-Public Decision-Making Model”Governments'Strategy on Responding to NIMBY Conflict

    Institute of Scientific and Technical Information of China (English)

    黄振威

    2015-01-01

    在保持决策高效率的同时控制决策风险是各国政府追求的目标。为了化解日益高涨的邻避冲突,政府决策和公众参与在寻求良性互动的过程中逐渐形成了两种基本决策模式:政府自主决策模式和公众参与决策模式。然中国的情况却与此并不相同,从 X市和Z市处置“PX”项目的对比案例来看,我国正在形成一种“半公众参与决策模式”,其特点可简单概括为“封闭决策+半开放的政策过程”。这种决策模式目前已成为政府防止决策失误,应对公众挑战的一个重要机制。%Risk-control while maintaining the high efficiency of decision-making is a goal pursued by governments all over the world.In order to resolve the rising NIMBY conflict,government decision-mak-ing and public participation have gradually formed two basic decision-making models in positive interac-tions:Government Autonomous Decision-Making Model and Public Decision-Making Model.However, Chinese experiences show considerable differences:a research on the contrast cases of“PX”proj ect from X City and Z City shows that China has been forming a “Semi-Public Decision-Making Model”,which can be summarized as “closed decision-making combining with semi-opening policy process”.This decision model has become an important mechanism to prevent decision failure and deal with public challenges in recent China.

  3. Downregulation of miR-151-5p contributes to increased susceptibility to arrhythmogenesis during myocardial infarction with estrogen deprivation.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available Estrogen deficiency is associated with increased incidence of cardiovascular diseases. But merely estrogen supplementary treatment can induce many severe complications such as breast cancer. The present study was designed to elucidate molecular mechanisms underlying increased susceptibility of arrhythmogenesis during myocardial infarction with estrogen deprivation, which provides us a new target to cure cardiac disease accompanied with estrogen deprivation. We successfully established a rat model of myocardial ischemia (MI accompanied with estrogen deprivation by coronary artery ligation and ovariectomy (OVX. Vulnerability and mortality of ventricular arrhythmias increased in estrogen deficiency rats compared to non estrogen deficiency rats when suffered MI, which was associated with down-regulation of microRNA-151-5p (miR-151-5p. Luciferase Reporter Assay demonstrated that miR-151-5p can bind to the 3'-UTR of FXYD1 (coding gene of phospholemman, PLM and inhibit its expression. We found that the expression of PLM was increased in (OVX+MI group compared with MI group. More changes such as down-regulation of Kir2.1/IK1, calcium overload had emerged in (OVX+MI group compared to MI group merely. Transfection of miR-151-5p into primary cultured myocytes decreased PLM levels and [Ca(2+]i, however, increased Kir2.1 levels. These effects were abolished by the antisense oligonucleotides against miR-151-5p. Co-immunoprecipitation and immunofluorescent experiments confirmed the co-localization between Kir2.1 and PLM in rat ventricular tissue. We conclude that the increased ventricular arrhythmias vulnerability in response to acute myocardial ischemia in rat is critically dependent upon down-regulation of miR-151-5p. These findings support the proposal that miR-151-5p could be a potential therapeutic target for the prevention of ischemic arrhythmias in the subjects with estrogen deficiency.

  4. Trust and governance in regional planning

    DEFF Research Database (Denmark)

    Tait, Malcolm; Hansen, Carsten Jahn

    2013-01-01

    This paper seeks to understand how planning systems respond to narratives of distrust, focusing on regional planning as a particularly contested field. Using a framework to explore how reforms have enhanced trust, analysis of cases in England and Denmark reveals two distinct actions: firstly......, a reliance on strengthening formal mechanisms of government, a feature common in England, and secondly, collaborative governance, as seen in Denmark. However, both strategies fail to adequately enhance trust in the values of regional planning, leaving it vulnerable to ideological critique as a worthwhile...

  5. “租税替代”、财政收入与政府的房地产政策%Rent-Tax Substitution, Fiscal Revenue and Government Real Estate Development Strategy

    Institute of Scientific and Technical Information of China (English)

    黄少安; 陈斌开; 刘姿彤

    2012-01-01

    本文从理论和实证两方面研究了房地产发展与政府财政收入之间的关系,揭示了“租税替代”原理。理论研究表明:在静态框架下,政府财政收入满足“租税等价”原理,即政府通过土地租金融资和通过企业税收融资是等价的,其总收入水平只取决于土地资源总量,与融资方式无关。在动态框架下,政府财政收入在长期内满足“租税等价”,在短期内存在“租税替代”关系,即政府来自于房地产的租金收入越高,来自于其它行业的税收收入越低。文章基于1998-2008年工业企业调查数据对“租税替代”机制进行了实证检验。研究发现,住房价格上涨将导致企业税收(增值税、所得税、主营业务税金及附加)和企业利润的全面下降,很好地支持了“租税替代”理论。本文还进一步考察了地方政府热衷于发展房地产的原因以及房地产片面发展对实体经济的不良影响,发现现行财政体制、政府官员短期行为以及官员政绩考核体系不合理是其背后最重要的原因。%This paper studies the relationship between real estate development and government fiscal revenue both theoretically and empirically. The theoretical model shows that the government's total revenue is determined by the amount of land in long run, while financing through land rents or corporate tax does not matter. In the short run, the Rent-Taxsubstitution mechanism characterizes the relationship of government revenue from land rents and corporate tax; the higher the land rent is, the lower the corporate tax will be. Based on 1998-2008 industrial enterprises survey data, this paper tests the “ Rent-Tax Substitution” mechanism empirieally, The results reveal that housing prices will result in a decline of eorporate tax (value added tax, income tax and business tax) and eorporate profits, whieh strongly supports the Rent-Tax substitution

  6. Decentralizing Agricultural Extension: Alternative Strategies.

    Science.gov (United States)

    Rivera, William M.

    1997-01-01

    Examines government strategies for decentralizing agricultural extension, concluding that such changes are largely determined by the country's constitutional status. Reviews decentralization guidelines for structural and fiscal reforms and participatory management systems. (SK)

  7. O ato de governar as tensões constitutivas do agir em saúde como desafio permanente de algumas estratégias gerenciais Governing tensions in the health action as a permanent challenge of some managerial strategies

    Directory of Open Access Journals (Sweden)

    Emerson Elias Merhy

    1999-01-01

    Full Text Available O autor procura sintetizar, neste ensaio, o que tem animado, recentemente, suas reflexões sobre o ato de governar estabelecimentos de saúde, em vários artigos e livros, tomando como desafio a tentativa de imprimir mudanças no dia-a-dia do fabricar os modelos de atenção à saúde, no interior das práticas dos trabalhadores, mesmo não tendo grande concentração de poder para a transformação, procurando então compreender como e por onde produzir poderes. Como explorar terrenos de potências no campo da saúde que estão presentes na conformação tensional de seu território de ação, fazendo-se uso das distintas ferramentas gerenciais disponíveis no campo das ciências e técnicas de governo, na saúde. Utiliza a atenção gerenciada para desenvolver certas análises.In the current essay, the author tries to synthesize what has livened him up lately in relation to his thinkings over the act of governing health organizations having several articles and books as a starting point, taking as a challenge the attempt of imprinting changes in the everyday life of the making of health attention models, in the core of the workers practices, even when a great concentration of power is not noticed as for transformation feasibility. Therefore there is a search to understand how and where power may be produced. How to explore terrains of potencies within the health field which are present in the tensional conformation of its action territory, using the managerial tools which are available in the area of science and government techniques - in health. Use managed care to developed analysis.

  8. Governing the City

    DEFF Research Database (Denmark)

    Kornberger, Martin

    2012-01-01

    Strategy frames the contemporary epistemological space of urbanism: major cities across the globe such as New York, London and Sydney invest time, energy and resources to craft urban strategies. Extensive empirical research projects have proposed a shift towards a strategic framework to manage...... cities. This theoretical curiosity is reflected in the rising interest in urban strategy from practice. For instance, the World Bank regularly organizes an Urban Strategy Speaker Series, while the powerful network CEOs for Cities lobbies for a strategic approach to urban development. Critical scholars...... such as Zukin diagnose not a shift in but a shift to strategic thinking in the contemporary city. This article poses the question: what makes strategy such an attractive ‘thought style’ in relation to imagining and managing cities? How can we understand the practice of urban strategy? And what are its intended...

  9. MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, S.Y. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Radiation-Oncology; HungKuang Univ., Taichung (China). Dept. of Biotechnology; Lin, K.C. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Oral and Maxillofacial Surgery; Chiou, J.F. [Taipei Medical Univ., Taipei (China). Dept. of Radiology; Taipei Medical Univ. Hospital, Taipei (China). Dept. of Radiation Oncology; Taipei Medical Univ. Hospital, Taipei (China). Dept. of Hospice and Palliative Center; Taipei Medical Univ. Hospital, Taipei (China). Cancer Center; Jeng, S.C. [Taipei Medical Univ. Hospital, Taipei (China). Dept. of Radiation Oncology; Cheng, W.H.; Chang, C.I. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Hemato-Ongology; Lin, W.C. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Div. of Thoracic Surgery; Wu, L.L. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Ophthalmology; Lee, H.L. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Radiation-Oncology; Chen, R.J. [National Taiwan Univ. Hospital and National Taiwan Univ., Taipei (China). Dept. of Obstetrics and Gynecology

    2013-08-15

    Background and purpose: Betel nut chewing is associated with oral cavity cancer in Taiwan. OC3 is an oral carcinoma cell line that was established from cells collected from a long-term betel nut chewer who does not smoke. After we found that microRNA-17-5p (miR-17-5p) is induced in OC3 cells, we used this cell line to examine the biological role(s) of this microRNA in response to exposure to ionizing radiation. Materials and methods: A combined SYBR green-based real-time PCR and oligonucleotide ligation assay was used to examine the expression of the miR-17 polycistron in irradiated OC3 cells. The roles of miR-17-5p and p21 were evaluated with specific antisense oligonucleotides (ODN) that were designed and used to inhibit their expression. Expression of the p21 protein was evaluated by Western blotting. The clonogenic assay and annexin V staining were used to evaluate cell survival and apoptosis, respectively. Cells in which miR-17-5p was stably knocked down were used to create ectopic xenografts to evaluate in vivo the role of miR-17-5p. Results: A radiation dose of 5 Gy significantly increased miR-17-5p expression in irradiated OC3 cells. Inhibition of miR-17-5p expression enhanced the radiosensitivity of the OC3 cells. We found that miR-17-5p downregulates radiation-induced p21 expression in OC3 cells and, by using a tumor xenograft model, it was found that p21 plays a critical role in increasing the radiosensitivity of OC3 cells in vitro and in vivo. Conclusion: miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells. (orig.)

  10. Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction.

    Science.gov (United States)

    Qi, Xu; Shao, Ming; Sun, Hongjing; Shen, Yue; Meng, Delong; Huo, Wei

    2017-04-21

    Activated microglia cells (MCs) are able to release a large amount of inflammatory cytokines after ischemic stroke, which exacerbates neuron damage. In this study, we explored the functional involvement of long non-coding RNA (lncRNA) SNHG14 and its potential regulatory mechanism in the activation of MCs. The mouse model of middle cerebral artery occlusion (MCAO) and microglia cell model of oxygen/glucose deprivation (OGD) were made. The expression of SNHG14, miR-145-5p and PLA2G4A protein expression was determined by quantitative real time PCR and western blot, respectively. Dual-luciferase assay was used to verify the direct binding of miR-145-5p and PLA2G4A. Flow cytometry was applied to measure neurons' apoptosis. SNHG14 highly expressed in ischemic cerebral tissues and BV-2 cells after OGD treatment. SNHG14 knockdown could remarkably inhibit BV-2 cells activation induced by OGD; while SNHG14 overexpression significantly promoted BV-2 cells activation, showing an increase of TNF-α and NO production and neurons' apoptosis rate. Additionally, SNHG14 knockdown promoted the expression of miR-145-5p and reduced PLA2G4A. Contrarily, SNHG14 overexpression inhibited miR-145-5p expression and increased PLA2G4A. Moreover, miR-145-5p overexpression also reversed the effect of OGD on BV-2 cells activation. Bioinformatics analysis and dual-luciferase assay supported that SNHG14 could bind directly to miR-145-5p and miR-145-5p-binding site was existed on 3'-UTR of PLA2G4A. MiR-145-5p mimic reversed the increase of PLA2G4A and reduced the high levels of TNF-α and NO in BV-2 cells induced by SNHG14 overexpression. SNHG14 increased the expression of PLA2G4A by inhibition of miR-145-5p, which resulted in the activation of MCs in cerebral infarction.

  11. Romanian government bond market

    Directory of Open Access Journals (Sweden)

    Cornelia POP

    2012-12-01

    Full Text Available The present paper aims to present the level of development reached by Romanian government bond market segment, as part of the country financial market. The analysis will be descriptive (the data series available for Romania are short, based on the secondary data offered by the official bodies involved in the process of issuing and trading the Romanian government bonds (Romanian Ministry of Public Finance, Romanian National Bank and Bucharest Stock Exchange, and also on secondary data provided by the Federation of European Stock Exchanges.To enhance the market credibility as a benchmark, a various combination of measures is necessary; among these measures are mentioned: the extension of the yield curve; the issuance calendars in order to improve transparency; increasing the disclosure of information on public debt issuance and statistics; holding regular meetings with dealers, institutional investors and rating agencies; introducing a system of primary dealers; establishing a repurchase (repo market in the government bond market. These measures will be discussed based on the evolution presented inside the paper.The paper conclude with the fact that, until now, the Romanian government bond market did not provide a benchmark for the domestic financial market and that further efforts are needed in order to increase the government bond market transparency and liquidity.

  12. Expression of antisense of microRNA-26a-5p in mesenchymal stem cells increases their therapeutic effects against cirrhosis

    Science.gov (United States)

    Chen, Li; Zeng, Wenhuan; Yang, Bo; Cui, Xiang; Feng, Cong; Wang, Lili; Wang, Hao; Zhou, Xuan; Li, Peng; Lv, Faqin; Li, Tanshi

    2017-01-01

    Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and has been shown to prevent cirrhosis during liver regeneration. Transplantation of mesenchymal stem cells (MSCs) reduces the development of cirrhosis after liver injury. However, the production and secretion of transplanted MSCs in liver were not studied yet. Here we found that the MSCs expressed low levels of HGF protein, but surprisingly high levels of HGF mRNA. Further investigation using bioinformatics analyses and luciferase reporter assay showed that MSCs expressed high levels of microRNA-26a-5p (miR-26a-5p), which targeted 3’-UTR of HGF mRNA to inhibit its protein translation. In vivo, miR-26a-5p-depleted MSCs were transplanted into mice with carbon tetrachloride (CCl4)-induced cirrhosis. We found that suppression of miR-26a-5p in MSCs further ameliorated the severity of liver fibrosis, reduced the portal hypertension and sodium retention, compared to transplantation of control MSCs. Hence, our study suggests that suppression of miR-26a-5p in MSCs may improve their therapeutic effects against cirrhosis through increasing HGF production.

  13. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes.

    Science.gov (United States)

    Wang, Pengchao; Zhao, Yuanyuan; Fan, Ruiwen; Chen, Tianzhi; Dong, Changsheng

    2016-06-24

    MicroRNAs (miRNAs) play an important role in regulating almost all biological processes. miRNAs bind to the 3' untranslated region (UTR) of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3' UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF) and Tyrosinase (TYR) were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5.

  14. A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.

    Directory of Open Access Journals (Sweden)

    Susanne Marije Kooistra

    Full Text Available Oncogene-induced senescence (OIS can occur in response to hyperactive oncogenic signals and is believed to be a fail-safe mechanism protecting against tumorigenesis. To identify new factors involved in OIS, we performed a screen for microRNAs that can overcome or inhibit OIS in human diploid fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16(INK4A and senescence-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA.

  15. miR-146a-5p inhibits TNF-α-induced adipogenesis via targeting insulin receptor in primary porcine adipocytes.

    Science.gov (United States)

    Wu, Di; Xi, Qian-Yun; Cheng, Xiao; Dong, Tao; Zhu, Xiao-Tong; Shu, Gang; Wang, Li-Na; Jiang, Qing-Yan; Zhang, Yong-Liang

    2016-08-01

    TNF-α is a multifunctional cytokine participating in immune disorders, inflammation, and tumor development with regulatory effects on energy metabolism. Our work focused on the function of TNF-α in adipogenesis of primary porcine adipocytes. TNF-α could suppress the insulin receptor (IR) at the mRNA and protein levels. Microarray analysis of TNF-α-treated porcine adipocytes was used to screen out 29 differentially expressed microRNAs (miRNAs), 13 of which were remarkably upregulated and 16 were intensely downregulated. These 29 differentially expressed miRNAs were predicted to mainly participate in the insulin signaling pathway, adipocytokine signaling pathway, and type 2 diabetes mellitus pathway by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. miR-146a-5p, reportedly involved in immunity and cancer relevant processes, was one of the most highly differentially expressed miRNAs after TNF-α treatment. Red Oil O staining and TG assay revealed that miR-146a-5p suppressed adipogenesis. A dual-luciferase reporter and siRNA assay verified that miR-146a-5p targeted IR and could inhibit its protein expression. miR-146a-5p was also validated to be involved in the insulin signaling pathway by reducing tyrosine phosphorylation of insulin receptor substrate-1. Our study provides the first evidence of miR-146a-5p targeting IR, which facilitates future studies related to obesity and diabetes using pig models.

  16. VCP/p97, down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu Liu

    Full Text Available Valosin containing protein (VCP/p97 plays various important roles in cells. Moreover, elevated expression of VCP in hepatocellular carcinoma (HCC is correlated with increased incidence of recurrence. But the role of VCP in HCC progression in vitro and in vivo is unclear. And there are few reports about the regulation mechanism on the expression of VCP in HCC. In this study, it was identified that the level of VCP was frequently increased in human HCC tissues. In addition, down-regulation of VCP with siRNAs could dramatically suppress the genesis and progression of tumor in vivo. It was found that miR-129-5p directly inhibited the expression of VCP in several HCC cell lines. Meanwhile, the level of VCP in HCC tissues was negatively associated with the level of miR-129-5p. Our further investigation showed that the enhanced expression of miR-129-5p also suppressed tumor growth in vivo. Moreover, it was revealed that miR-129-5p could inhibit the degradation of IκBα and increase the apoptosis and reduce the migration of HCC cells by suppressing the expression of VCP. Our results revealed that the expression of VCP was directly regulated by miR-129-5p and this regulation played an important role in the progression of HCC.

  17. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes

    Directory of Open Access Journals (Sweden)

    Pengchao Wang

    2016-06-01

    Full Text Available MicroRNAs (miRNAs play an important role in regulating almost all biological processes. miRNAs bind to the 3′ untranslated region (UTR of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3′ UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF and Tyrosinase (TYR were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5.

  18. An Innovative Approach for E-Government Transformation

    CERN Document Server

    Al-Khouri, Ali M

    2011-01-01

    Despite the immeasurable investment in e-government initiatives throughout the world, such initiatives have yet to succeed in fully meeting expectations and desired outcomes. A key objective of this research article is to support the government of the UAE in realizing its vision of e-government transformation. It presents an innovative framework to support e-government implementation, which was developed from a practitioner's perspective and based on learnings from numerous e-government practices around the globe. The framework presents an approach to guide governments worldwide, and UAE in particular, to develop a top down strategy and leverage technology in order realize its long term goal of e-government transformation. The study also outlines the potential role of modern national identity schemes in enabling the transformation of traditional identities into digital identities. The work presented in this study is envisaged to help bridge the gap between policy makers and implementers, by providing greater ...

  19. [Citizen security observatories: tools for decision making and governability].

    Science.gov (United States)

    Sánchez-Rentería, Gabriela; Bonilla-Escobar, Francisco Javier; Fandiño-Losada, Andrés; Gutiérrez-Martinez, María Isabel

    2016-06-01

    The need for good governability to promote countries development has been becoming the focus of governments. Latin America has political systems in crisis of governability caused by the inability of strategic actors to solve conflicts based on rules and procedures. The present review aims to describe how the creation of violence surveillance systems (observatories) contributes to strengthening governability and the creation of effective public policies. It was developed an analysis of the required components for the existence of governability and its relationship with the role of observatories in cities to provide reliable, timely and representative information that allows the formulation of strategies and policies. Governability is enriched with the legitimacy granted by the public from the results obtained by the governments in the formulation, implementation, evaluation of public policies and the evidence-based decisions in public health.

  20. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

    Science.gov (United States)

    Tao, Shi-Cong; Yuan, Ting; Zhang, Yue-Lei; Yin, Wen-Jing; Guo, Shang-Chun; Zhang, Chang-Qing

    2017-01-01

    OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p. Exosomes derived from SMSCs or SMSC-140s (SMSC-Exos or SMSC-140-Exos) were isolated and identified. Proliferation, migration and ECM secretion were measured in vitro and compared between groups. The mechanism involving alternative Wnt signalling and activation of Yes-associated protein (YAP) was investigated using lentivirus, oligonucleotides or chemical drugs. The preventative effect of exosomes in vivo was measured using Safranin-O and Fast green staining and immunohistochemical staining. RESULTS: Wnt5a and Wnt5b carried by exosomes activated YAP via the alternative Wnt signalling pathway and enhanced proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion. Highly-expressed miR-140-5p blocked this side-effect via RalA. SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC-140-Exos successfully prevented OA in a rat model. CONCLUSIONS: These findings highlight the promising potential of SMSC-140-Exos in preventing OA. We first found a potential source of exosomes and studied their merits and shortcomings. Based on our understanding of the molecular mechanism, we overcame the shortcomings by modifying the exosomes. Such exosomes derived from modified cells hold potential as future therapeutic strategies. PMID:28042326

  1. Why Governments Intervene

    DEFF Research Database (Denmark)

    Brown, Dana; Knudsen, Jette Steen

    Why are national governments increasingly adopting policies on Corporate Social Responsibility (CSR)? What is the rationale and purpose of these policies? Scholars from various disciplines including Political Science, International Relations and Management Studies have offered explanations...... for this phenomenon. Research has tended either to rely on cross-country comparisons that generalize tendencies within given countries; or to over-generalize global trends. The current paper analyzes particular CSR policies in two countries – Denmark and the United Kingdom. We find that the rationales for government...... initiatives on CSR are neither consistent across countries or within them. Instead, CSR policies are utilized to address multiple issues crossing various areas of governance, including domestic social policy, global competitiveness policies and foreign policy....

  2. Pension Fund Governing Board

    CERN Document Server

    HR Department

    2008-01-01

    Note The CERN pension scheme is based on the principle of defined benefits, so beneficiaries continue to receive the benefits to which they are entitled in accordance with the Rules of the Pension Fund. This means that pension entitlements under the Rules are not directly affected by the financial crisis and the current economic situation. However, the adjustment of pensions to the cost of living is not automatic and, under the method applied since 2006, must take into account the Fund’s financial position. Meeting of the Pension Fund Governing Board The Pension Fund Governing Board held its eighth meeting at ESO in Garching, Germany (near Munich) on 24 October 2008. Before starting its work, the Governing Board had the privilege of hearing an opening address by Professor Tim de Zeeuw, the Director General of ESO. Professor de Zeeuw described the mission of ESO and the ambitious projects of his organisation, which performs astronomy observations using telescopes located in...

  3. E-governance justified

    Directory of Open Access Journals (Sweden)

    William Akotam Agangiba

    2013-03-01

    Full Text Available Information and Communication Technology today has become an indispensable part in our lives, gaining wide application in human activities. This is due to the fact that, its use is less expensive, more secure, and allows speedy information transmission and access. It serves as a good base for the development and success of today’s relatively young technologies. It has relieved people of manual day-to-day activities in such areas as businesses organizations, transport industry, teaching and research, banking, broadcasting, entertainment amongst other. This paper takes an overview study of e-governance, one of the most demanding applications of information and communication technology for public services. The paper summarizes the concept of e-governance, its major essence and some ongoing e-governance activities in some parts of the world.

  4. Managing e-government

    DEFF Research Database (Denmark)

    Rose, Jeremy; Persson, John Stouby; Heeager, Lise Tordrup

    2015-01-01

    Public sector managers take much of the responsibility for selecting, commissioning, implementing and realising benefits from information technology (IT) projects. However, e-Government initiatives often suffer from complexity, vision failure, lack of goal clarity and insufficient commitment....... These problems may stem from value traditions that are deeply ingrained in managers' cultural environments but not always in harmony with each other. A first step towards working with value complexity is to understand it; we synthesise a model of value positions for e-Government derived from major traditions...... in the public administration literature. Four value positions relevant to e-Government together with their IT assumptions are identified; they reflect the ideals of professionalism, efficiency, service and engagement. A qualitative investigation of Danish local authority managers displays both value congruence...

  5. 'Joined Up' Local Governments?

    DEFF Research Database (Denmark)

    Bjørnå, Hilde; Casale, Donatella; Hajnal, Gyorgy;

    eforms inspired by NPM have raised many challenges to governments, such as time lags between implementation and (any) results, fragmentation due to unbundling monolithic organizations and mediocre support from public sector stakeholders (Christensen/Lægreid 2007, Dunleavy et al. 2006, Hood....../Dixon 2015). In addition, singular events like the current financial crisis (Peters 2011) shed a new light on previous reforms. Today we find that 'Joined-up government' (JUG) modernization programs (as one strand of Post-NPM) are increasingly implemented as a reaction to the dysfunctionalities of NPM...... measures (6 2004). JUG involves an emphasis on coordinating governmental activities, for example through partnerships and horizontal governing approaches, to eliminate contradictions between different policies, and to deliver integrated and seamless services from a citizen’s perspective (Lægreid et al...

  6. Governing To‐day

    DEFF Research Database (Denmark)

    Turner, Kevin

    2014-01-01

    Governing To-day denotes a domain of research, and what the thesis undertakes is a theoretical discussion of some questions of method vis-à-vis researching this domain. There are two aspects to the title that enfold one another. Firstly, “governing to-day” signposts that it is to...... as its reference point and means of critique the “will not to be governed like that”. Consequently, the approach thus outlined is firmly situated within that rather loosely affiliated body of work that goes under the title studies in governmentality. Studies in governmentality have their point...... of departure in the research and writing of the French philosopher and historian, Michel Foucault. It is primarily within the writings of Foucault that the thesis seeks to find a workaround to the problem thrown forth by the aforementioned questions of method....

  7. World Government: Utopia?

    Directory of Open Access Journals (Sweden)

    Vahram Ayvazyan

    2012-07-01

    Full Text Available The aim of this paper is to analyze the possibility of having a world government, which world has been facing overarching changes since the end of Cold war, where bipolar world order has evolved into multipolar system through unipolarity. Analysis method in this paper have the sistematics: discussion of human nature and philosophical dimensions vis-à-vis individual, society and government, as well as society of societies; then briefly analyse globalization, the impact of individuals on interdependency of the current international arena and examine the individualism as the ongoing ideology “by individuals and for individuals.”; and then take the conclusion that the world government is not a utopia

  8. Corporate governance and liquidity

    DEFF Research Database (Denmark)

    Farooq, Omar; Derrabi, Mohamed; Naciri, Monir

    2012-01-01

    This paper examines the impact of corporate governance mechanisms on liquidity in the MENA region, i.e. Morocco, Egypt, Saudi Arabia, United Arab Emirates, Jordan, Kuwait, and Bahrain. Using turnover as a proxy for liquidity, we document significant difference in liquidity between the pre......- and the post-crisis periods in the MENA region. In addition, our results show that bulk of this reduction in turnover can be explained due to weaknesses of corporate governance mechanisms. For example, that dividend payout ratio and choice of auditors – proxies for agency problems – can explain the entire...... difference in liquidity between the two periods. Furthermore, our results indicate that more than 50% of this difference between the two periods can be explained by operational and informational complexity of a firm – proxy for transparency. We argue that poor corporate governance mechanisms increase...

  9. 世界银行治理结构改革与中国的应对策略∗%The Reform of the World Bank Governance Structure and China’ s strategies

    Institute of Scientific and Technical Information of China (English)

    叶扬; 张文

    2015-01-01

    世界银行在全球经济治理中发挥着重要作用,但随着新兴经济体的崛起和近年来金融危机、债务危机频发,世界银行治理结构所存在的制度性缺陷显露无遗,相应改革势在必行。但是,由于世界银行具有公共组织与股份公司的双重属性,使得改革方向出现分歧,改革进程推进缓慢。从根本上说,世界银行改革中发达国家与发展中国家并不存在不可调和的利益冲突,在减贫等问题上双方存在着合作的基础。中国应积极推进世界银行治理结构改革:首先,必须明确“负责任、有作为的大国”定位,表现出推动改革的积极态度;其次,要紧密围绕“发展”主题,注重长远利益;再次,要加强对世界银行人事安排的参与;最后,要积极构建世界银行框架下发展中国家沟通与合作的正式协调机制。%The World Bank plays an important role in global economic governance. With the rise of emerging economies and frequent occurrence of financial crisis, institutional defects of the World Bank ’ s governance structure become more and more apparent. Therefore, corresponding reform is imperative. The biggest obstacle to reform is that the World Bank is not only public organization but also a corporation. The dual attributes lead to the disagreement on the reform direction. However, the conflict between the developed countries and the developing countries is not irreconcilable. They can cooperate on many issues, such as alleviating poverty. China should positively promote the reform of the World Bank governance structure. Firstly, China must clear the position of“responsible and capable power” and show a positive attitude to promote the reform. Secondly, closely focus on the theme of development and concern long⁃term interests. Thirdly, step up participation of personnel arrangements in the World Bank. Finally, actively build a formal coordination mechanism

  10. Microblogging Strategies of the Local Government Seen from "Chengdu Release"%从“成都发布”看地方政府微博的发布策略

    Institute of Scientific and Technical Information of China (English)

    曹艳; 吴玉贞

    2012-01-01

    "Chengdu Release", an official micro blog site on Sina Weibo. com established by Chengdu Peo- ple' s Government Information Office, is the hottest one of the government agencies. On the basis of literature re- search, case studies and textual analyses of its positioning, team management, releasing patterns and contents as well as interaction with the public, it can be found that "Chengdu Release" has a definite positioning, good transparency, and strong credibility with its main characteristics as follows: its open, authoritative and sincere attitude to the public ; its rich content closely connected with the public need; its plain and lively language, and even internet slangs; its emphasis on communication with the public, dealing with the public views and reviews in good faith and its efforts to solve problems for the public.%成都市人民政府新闻办公室在新浪微博开设的官方微博“成都发布”是国内最火的政府机构微博之一。通过文献研究法、案例分析法和文本分析法对该微博的定位、经营团队管理、发布规律和发布内容,以及与公众的互动等方面进行分析,发现“成都发布”定位清晰,透明度大,公信力较强。“成都发布”的主要特色与表现是开放、权威,以真诚的态度面对公众;内容丰富,结合公众需要;言语平民化、网络化和活泼化;注重与公众的交流,诚信看待公众的意见和评论,努力为公众解决问题等。

  11. Governing EU employment policy

    DEFF Research Database (Denmark)

    Sørensen, Eva; Triantafillou, Peter; Damgaard, Bodil

    2015-01-01

    In the European Union (EU), employment policy is a prerogative of the member states. Therefore the EU's ability to govern in this area depends on its capability to involve national governments and relevant stakeholders in a collaborative effort to formulate and implement shared policy objectives....... Drawing an analytical distinction between cooperation, coordination and collaboration, the article analyses the formulation and implementation of EU employment policies. It concludes that while the formulation of policy objectives and the discussion of national policy approaches do involve elements...

  12. Governing IT outsourcing relationships

    CERN Document Server

    Kuhlmann, Daniel

    2012-01-01

    Hauptbeschreibung The dynamics of the relationship between service recipient and service provider in IS outsourcing relationships recently gained increased attention as relationships are believed to have a considerable influence on IS outsourcing success. This study adds to this growing field of interest by developing an IS outsourcing relationship framework in the form of a process model. Three rather disjointed areas of research, namely contractual governance, relational norms, and control, have been set in a common context by interrelating them as the three main governance modes

  13. Repumping and spectroscopy of laser-cooled Sr atoms using the (5s5p)3P2 - (5s4d)3D2 transition

    CERN Document Server

    Mickelson, P G; Anzel, P; DeSalvo, B J; Nagel, S B; Traverso, A J; Yan, M; Killian, T C

    2009-01-01

    We describe repumping and spectroscopy of laser-cooled strontium (Sr) atoms using the (5s5p)3P2 - (5s4d)3D2 transition. Atom number in a magneto-optical trap is enhanced by driving this transition because Sr atoms that have decayed into the (5s5p)3P2 dark state are repumped back into the (5s2)1S0 ground state. Spectroscopy of 84Sr, 86Sr, 87Sr, and 88Sr improves the value of the (5s5p)3P2 - (5s4d)3D2 transition frequency for 88Sr and determines the isotope shifts for the transition.

  14. Repumping and spectroscopy of laser-cooled Sr atoms using the (5s5p)3P2-(5s4d)3D2 transition

    Science.gov (United States)

    Mickelson, P. G.; Martinez de Escobar, Y. N.; Anzel, P.; De Salvo, B. J.; Nagel, S. B.; Traverso, A. J.; Yan, M.; Killian, T. C.

    2009-12-01

    We describe repumping and spectroscopy of laser-cooled strontium (Sr) atoms using the (5s5p)3P2-(5s4d)3D2 transition. Atom number in a magneto-optical trap is enhanced by driving this transition because Sr atoms that have decayed into the (5s5p)3P2 dark state are repumped back into the (5s2)1S0 ground state. Spectroscopy of 84Sr, 86Sr, 87Sr and 88Sr improves the value of the (5s5p)3P2-(5s4d)3D2 transition frequency and determines the isotope shifts for the transition accurately enough to guide laser-cooling experiments with less abundant isotopes.

  15. Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels.

    Science.gov (United States)

    Kinoshita, Chisato; Aoyama, Koji; Matsumura, Nobuko; Kikuchi-Utsumi, Kazue; Watabe, Masahiko; Nakaki, Toshio

    2014-05-07

    Glutathione (GSH) is a key antioxidant that plays an important neuroprotective role in the brain. Decreased GSH levels are associated with neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Here we show that a diurnal fluctuation of GSH levels is correlated with neuroprotective activity against oxidative stress in dopaminergic cells. In addition, we found that the cysteine transporter excitatory amino acid carrier 1 (EAAC1), which is involved in neuronal GSH synthesis, is negatively regulated by the microRNA miR-96-5p, which exhibits a diurnal rhythm. Blocking miR-96-5p by intracerebroventricular administration of an inhibitor increased the level of EAAC1 as well as that of GSH and had a neuroprotective effect against oxidative stress in the mouse substantia nigra. Our results suggest that the diurnal rhythm of miR-96-5p may play a role in neuroprotection by regulating neuronal GSH levels via EAAC1.

  16. MiR-21-5p Links Epithelial-Mesenchymal Transition Phenotype with Stem-Like Cell Signatures via AKT Signaling in Keloid Keratinocytes

    Science.gov (United States)

    Yan, Li; Cao, Rui; Liu, Yuanbo; Wang, Lianzhao; Pan, Bo; Lv, Xiaoyan; Jiao, Hu; Zhuang, Qiang; Sun, Xuejian; Xiao, Ran

    2016-09-01

    Keloid is the abnormal wound healing puzzled by the aggressive growth and high recurrence rate due to its unrevealed key pathogenic mechanism. MicroRNAs contribute to a series of biological processes including epithelial-mesenchymal transition (EMT) and cells stemness involved in fibrotic disease. Here, using microRNAs microarray analysis we found mir-21-5p was significantly up-regulated in keloid epidermis. To investigate the role of miR-21-5p in keloid pathogenesis, we transfected miR-21-5p mimic or inhibitor in keloid keratinocytes and examined the abilities of cell proliferation, apoptosis, migration and invasion, the expressions of EMT-related markers vimentin and E-cadherin and stem-like cells-associated markers CD44 and ALDH1, and the involvement of PTEN and the signaling of AKT and ERK. Our results demonstrated that up-regulation or knockdown of miR-21-5p significantly increased or decreased the migration, invasion and sphere-forming abilities of keloid keratinocytes, and the phenotype of EMT and cells stemness were enhanced or reduced as well. Furthermore, PTEN and p-AKT were shown to participate in the regulation of miR-21-5p on EMT phenotypes and stemness signatures of keloid keratinocytes, which might account for the invasion and recurrence of keloids. This molecular mechanism of miR-21-5p on keloid keratinocytes linked EMT with cells stemness and implicated novel therapeutic targets for keloids.

  17. hsa-miR-125a-5p Enhances Invasion in Non-small Cell Lung Carcinoma Cell Lines by Upregulating Rock-1

    Directory of Open Access Journals (Sweden)

    Lili JIANG

    2009-10-01

    Full Text Available Background and objective MicroRNAs (miRNAs are endogenous, non-coding small RNA in eukaryotes. They recognize their target sites by incomplete base pairing and posttranscriptionally regulate gene expression, and function on a lot of complex vital processes of organisms. The objective of this work is to study how hsa-miR-125a-5p enhances the invasive ability of lung cancer cells. Methods The target gene and its target sites of hsa-miR-125a-5p were predicted by microRNA.org. We investigated Rock-1 mRNA and protein expressions by RT-PCR and Western blot according to the result of prediction further. The invasive ability of A549 cells, which were transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide after being blocked by anti-Rock-1, was observed by Transwell. Results With RT-PCR and Western blot, Rock-1 mRNA and protein were both increased in A549 cells transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide and were both decreased in the cells which transfected with antisense vs control groups. The invasive ability of A549 cells transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide were weakened after being blocked by anti-Rock-1, vs non-blocking group by Transwell test. Conclusion hsa-miR-125a-5p could up-regulate Rock-1 and enhance invasion in lung cancer cells.

  18. Distinct plasma-membrane PtdIns(4)P and PtdIns(4,5)P2 dynamics in secretagogue-stimulated beta-cells.

    Science.gov (United States)

    Wuttke, Anne; Sågetorp, Jenny; Tengholm, Anders

    2010-05-01

    Phosphoinositides regulate numerous processes in various subcellular compartments. Whereas many stimuli trigger changes in the plasma-membrane PtdIns(4,5)P(2) concentration, little is known about its precursor, PtdIns(4)P, in particular whether there are stimulus-induced alterations independent of those of PtdIns(4,5)P(2). We investigated plasma-membrane PtdIns(4)P and PtdIns(4,5)P(2) dynamics in insulin-secreting MIN6 cells using fluorescent translocation biosensors and total internal reflection microscopy. Loss of PtdIns(4,5)P(2) induced by phospholipase C (PLC)-activating receptor agonists or stimulatory glucose concentrations was paralleled by increased PtdIns(4)P levels. In addition, glucose-stimulated cells regularly showed anti-synchronous oscillations of the two lipids. Whereas glucose-induced PtdIns(4)P elevation required voltage-gated Ca(2+) entry and was mimicked by membrane-depolarizing stimuli, the receptor-induced response was Ca(2+) independent, but sensitive to protein kinase C (PKC) inhibition and mimicked by phorbol ester stimulation. We conclude that glucose and PLC-activating receptor stimuli trigger Ca(2+)- and PKC-dependent changes in the plasma-membrane PtdIns(4)P concentration that are independent of the effects on PtdIns(4,5)P(2). These findings indicate that enhanced formation of PtdIns(4)P, apart from ensuring efficient replenishment of the PtdIns(4,5)P(2) pool, might serve an independent signalling function by regulating the association of PtdIns(4)P-binding proteins with the plasma membrane.

  19. ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors.

    Science.gov (United States)

    MacMillan, D; Kennedy, C; McCarron, J G

    2012-11-01

    Adenosine 5'-triphosphate (ATP) mediates a variety of biological functions following nerve-evoked release, via activation of either G-protein-coupled P2Y- or ligand-gated P2X receptors. In smooth muscle, ATP, acting via P2Y receptors (P2YR), may act as an inhibitory neurotransmitter. The underlying mechanism(s) remain unclear, but have been proposed to involve the production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] by phospholipase C (PLC), to evoke Ca(2+) release from the internal store and stimulation of Ca(2+)-activated potassium (K(Ca)) channels to cause membrane hyperpolarization. This mechanism requires Ca(2+) release from the store. However, in the present study, ATP evoked transient Ca(2+) increases in only ∼10% of voltage-clamped single smooth muscle cells. These results do not support activation of K(Ca) as the major mechanism underlying inhibition of smooth muscle activity. Interestingly, ATP inhibited Ins(1,4,5)P(3)-evoked Ca(2+) release in cells that did not show a Ca(2+) rise in response to purinergic activation. The reduction in Ins(1,4,5)P(3)-evoked Ca(2+) release was not mimicked by adenosine and therefore, cannot be explained by hydrolysis of ATP to adenosine. The reduction in Ins(1,4,5)P(3)-evoked Ca(2+) release was, however, also observed with its primary metabolite, ADP, and blocked by the P2Y(1)R antagonist, MRS2179, and the G protein inhibitor, GDPβS, but not by PLC inhibition. The present study demonstrates a novel inhibitory effect of P2Y(1)R activation on Ins(1,4,5)P(3)-evoked Ca(2+) release, such that purinergic stimulation acts to prevent Ins(1,4,5)P(3)-mediated increases in excitability in smooth muscle and promote relaxation.

  20. miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma.

    Science.gov (United States)

    Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; Di Gennaro, Gianfranco; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-05-10

    The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30-50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs.