Distribution by Scientific Domains

Kinds of Regulatory

  • interferon regulatory

  • Terms modified by Regulatory

  • regulatory action
  • regulatory activity
  • regulatory agencies
  • regulatory agency
  • regulatory approach
  • regulatory approval
  • regulatory aspect
  • regulatory assessment
  • regulatory authority
  • regulatory body
  • regulatory burden
  • regulatory capacity
  • regulatory cascade
  • regulatory cd4+cd25+ t cell
  • regulatory cell
  • regulatory change
  • regulatory circuit
  • regulatory competition
  • regulatory compliance
  • regulatory component
  • regulatory condition
  • regulatory constraint
  • regulatory context
  • regulatory control
  • regulatory cytokine
  • regulatory decision
  • regulatory difference
  • regulatory domain
  • regulatory effect
  • regulatory effects
  • regulatory element
  • regulatory element binding protein
  • regulatory element-binding protein
  • regulatory environment
  • regulatory enzyme
  • regulatory event
  • regulatory evolution
  • regulatory factor
  • regulatory failure
  • regulatory focus
  • regulatory framework
  • regulatory frameworks
  • regulatory function
  • regulatory gene
  • regulatory guidance
  • regulatory guideline
  • regulatory hierarchy
  • regulatory impact assessment
  • regulatory influence
  • regulatory initiative
  • regulatory institution
  • regulatory instruments
  • regulatory interaction
  • regulatory intervention
  • regulatory issues
  • regulatory level
  • regulatory light chain
  • regulatory limit
  • regulatory loop
  • regulatory measure
  • regulatory mechanism
  • regulatory mechanism underlying
  • regulatory mode
  • regulatory model
  • regulatory module
  • regulatory molecule
  • regulatory motif
  • regulatory mutation
  • regulatory network
  • regulatory neuropeptide
  • regulatory oversight
  • regulatory pathway
  • regulatory pattern
  • regulatory peptide
  • regulatory performance
  • regulatory phenotype
  • regulatory policy
  • regulatory polymorphism
  • regulatory power
  • regulatory practice
  • regulatory pressure
  • regulatory process
  • regulatory program
  • regulatory property
  • regulatory protein
  • regulatory provision
  • regulatory regime
  • regulatory region
  • regulatory regions
  • regulatory requirement
  • regulatory response
  • regulatory restriction
  • regulatory review
  • regulatory risk
  • regulatory rna
  • regulatory role
  • regulatory scheme
  • regulatory scrutiny
  • regulatory sequence
  • regulatory signal
  • regulatory site
  • regulatory standards
  • regulatory state
  • regulatory step
  • regulatory structure
  • regulatory subunit
  • regulatory system
  • regulatory t cell
  • regulatory t cell response
  • regulatory t-cell function
  • regulatory variation
  • regulatory volume decrease

  • Selected Abstracts


    Can the European regulatory state be managed? The European Union (EU) and its member states have looked at better regulation as a possible answer to this difficult question. This emerging public policy presents challenges to scholars of public management and administrative reforms, but also opportunities. In this conceptual article, we start from the problems created by the value-laden discourse used by policy-makers in this area, and provide a definition and a framework that are suitable for empirical/explanatory research. We then show how public administration scholars could usefully bring better regulation into their research agendas. To be more specific, we situate better regulation in the context of the academic debates on the New Public Management, the political control of bureaucracies, evidence-based policy, and the regulatory state in Europe. [source]

    Regulatory reform of the UK gas market: The sase of the storage auction

    FISCAL STUDIES, Issue 2 2001
    David Hawdon
    Abstract The UK gas industry has undergone major changes since it was privatised in 1986 as a fully integrated monopoly. The most significant of these has occurred not as a result of the privatisation legislation but by the intervention of the ordinary competition authorities in support of an active industry regulator. While price capping continues to be used as the primary instrument for welfare protection against the still substantial monopolistic powers of the incumbent, new competition (which has been positively encouraged) has had the greater impact on prices and choice. Recently, however, the regulator has encouraged the use of auctions for the sale of storage capacity. This paper considers the merits of auctions and makes a tentative evaluation of their effectiveness. Further use of auctions is recommended but reserve prices are considered inappropriate where monopoly power still remains. [source]

    Institutions and Sustainable Transport: Regulatory Reform in Advanced Economies , Edited by Piet Rietveld and Roger R. Stough

    GROWTH AND CHANGE, Issue 1 2009
    Christopher Kissling
    First page of article [source]

    Escaping the Regulatory Net: Why Regulatory Reform Can Fail Consumers,

    LAW & POLICY, Issue 4 2005
    This paper considers the impact of recent reforms to the UK food safety régime and considers whether the reforms have been able to deliver their promised benefits and if not, why not. Empirically, the paper examines the UK Food Standards Agency's (FSA) reforms to the régime managing food allergen risks, and the extent to which those reforms have reflected the FSA's guiding principle of "putting consumers first". The paper finds that the operationalization of that guiding principle was mitigated by a number of factors, including: interpretative flexibility in representing consumer interests; the institutional structure and character of the régime; the political and cultural environment in which the régime operated; and normative uncertainties about the allocation of rights and responsibilities in managing risks. The paper concludes that risk regulation reforms are likely to fail in prioritizing consumer interests unless such factors are taken into account. [source]

    Regulatory reform and managerial choice: an analysis of the cost savings from airline deregulation

    Margaret Peteraf
    This paper explores the question of how the differential exercise of managerial choice can facilitate organizational adaptation and improve efficiency over periods of regulatory change. We address this question in the context of the US airline industry, with a detailed decomposition of an airline cost function. Our findings suggest that managers employ choice in unconstrained domains to counteract the effects of constrained or pre-determined choices. This is an adaptive mechanism that helps firms adjust to environmental change or maneuver over a rugged landscape. We view this as a type of dynamic managerial capability for achieving dynamic fit under changing conditions. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Legitimacy for a Supranational European Political Order,Derivative, Regulatory or Deliberative?

    RATIO JURIS, Issue 1 2002
    Massimo La Torre
    This paper discusses some models purported to legitimise a European supranational legal order. In particular, the author focuses on an application of the so-called regulatory model to the complex structure of the European Community and the European Union. First of all, he tackles the very concept of legitimacy, contrasting it with both efficacy and efficiency. Secondly, he summarises the most prominent positions in the long-standing debate on the sources of legitimation for the European Community. Thirdly, in this perspective, he analyses several, sometimes contradictory, notions of the rule of law. His contention is that we can single out five fundamental notions of the rule of law and that some but not all of them are incompatible with or oppose democracy. Finally, the paper addresses the regulatory model as a possible application of the rule of the law to the European supranational order. The conclusion is that the regulatory model should be rejected if it is presented as an alternative to classical democratic thought, though it might be fruitful if reshaped differently and no longer assessed from a functionalist standpoint of deliberation. [source]

    Remediation process optimization: A status report

    REMEDIATION, Issue 3 2007
    Sriram Madabhushi
    There are hundreds of contaminated sites with remediation systems that require evaluation and modification to accomplish cleanup goals. These systems are operating well past projected cleanup schedules, cost more than projected to operate, and may not be as protective of human health and the environment as planned. Remediation process optimization (RPO) is an effective method to assess the progress of a system toward achieving cleanup goals within desired time frames and to make the necessary changes in order to reach those goals. Eight main components to the RPO process are evaluated during a review and an implementation plan of recommended changes to the system is developed. Follow-up and tracking are essential to successful RPO programs. In this article, the authors present a summary of a recent Technical and Regulatory (TechReg) Guidance Document (Interstate Technology and Regulatory Council [ITRC], 2004) and related Technology Overview Series on Advanced Topics in RPO (ITRC, 2006) in a distilled form. © 2007 Wiley Periodicals, Inc. [source]

    ORIGINAL ARTICLE: Role of Regulatory and Angiogenic Cytokines in Invasion of Trophoblastic Cells

    Valeria Dubinsky
    Citation Dubinsky V, Poehlmann TG, Suman P, Gentile T, Markert UR, Gutierrez G. Role of regulatory and angiogenic cytokines in invasion of trophoblastic cells. Am J Reprod Immunol 2010; 63: 193,199 Problem, Trophoblast invasion is a temporally and locally restricted process, which regulates implantation and oxygen arrival to the embryo through the dialog with spiral artery endothelium. Trophoblast factors with angiogenic potential are activated by hypoxia. Their capacities to induce proliferation, migration, and invasion of trophoblastic cells have been investigated. Method of study, The expression of interleukin (IL)-6, CD126, CD130, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1, (HIF-1,) has been silenced in JEG-3 choriocarcinoma cells by using siRNA. Silencing efficacy has been assessed by ELISA, PCR or Western blotting. Proliferation has been measured by flow cytometry, migration by a transwell assay, and invasion by a Matrigel assay. Results, Proliferation was significantly reduced by silencing of CD126 or CD130, migration by silencing of IL-6, VEGF, or HIF-1,, and invasion by silencing of IL-6 and HIF-1,. Conclusion, The expression of IL-6, VEGF, and HIF-1, in trophoblastic cells is involved in the control of trophoblast invasion and migration. [source]

    In the Wake of ,Good Governance': Impact Assessments and the Politicisation of Statutory Interpretation

    THE MODERN LAW REVIEW, Issue 3 2008
    Roderick Munday
    For some time ,regulatory reform' has been a government watchword, and the streamlining and improved quality of regulation its professed ambition. Impact assessments (formerly known as regulatory impact assessments) are a significant ingredient in these governmental initiatives, now promoted by the newly created Department for Business, Enterprise and Regulatory Reform. Just as they have come to refer rather freely to the Explanatory Notes that now accompany all public Acts of Parliament, judges have also begun to invoke impact assessments when construing legislation. This paper investigates the extent of this practice and the manner in which judges employ impact assessments. It warns of the potential consequences if the judiciary avails itself too readily of these highly politicised, and sometimes deceptive, documents. ,The aim of good prose words is to mean what they say.' G. K. Chesterton, Daily News 22 April 1905 [source]

    The Changed Balance of Regulatory and Naive T Cells Promotes Tolerance after TLI and Anti-T-Cell Antibody Conditioning

    R. G. Nador
    The goal of the study was to determine how the changed balance of host naïve and regulatory T cells observed after conditioning with total lymphoid irradiation (TLI) and antithymocyte serum (ATS) promotes tolerance to combined organ and bone marrow transplants. Although previous studies showed that tolerance was dependent on host natural killer T (NKT) cells, this study shows that there is an additional dependence on host CD4+CD25+ Treg cells. Depletion of the latter cells before conditioning resulted in rapid rejection of bone marrow and organ allografts. The balance of T-cell subsets changed after TLI and ATS with TLI favoring mainly NKT cells and ATS favoring mainly Treg cells. Combined modalities reduced the conventional naïve CD4+ T cells 2800-fold. The host type Treg cells that persisted in the stable chimeras had the capacity to suppress alloreactivity to both donor and third party cells in the mixed leukocyte reaction. In conclusion, tolerance induction after conditioning in this model depends upon the ability of naturally occurring regulatory NKT and Treg cells to suppress the residual alloreactive T cells that are capable of rejecting grafts. [source]

    Isolated CD39 Expression on CD4+ T Cells Denotes both Regulatory and Memory Populations

    Q. Zhou
    Foxp3+ regulatory T cells (Tregs) express both ectoenzymes CD39 and CD73, which in tandem hydrolyze pericellular ATP into adenosine, an immunoinhibitory molecule that contributes to Treg suppressive function. Using Foxp3GFP knockin mice, we noted that the mouse CD4+CD39+ T-cell pool contains two roughly equal size Foxp3+ and Foxp3, populations. While Foxp3+CD39+ cells are CD73bright and are the bone fide Tregs, Foxp3,CD39+ cells do not have suppressive activity and are CD44+CD62L,CD25,CD73dim/,, exhibiting memory cell phenotype. Functionally, CD39 expression on memory and Treg cells confers protection against ATP-induced apoptosis. Compared with Foxp3,CD39, naïve T cells, Foxp3,CD39+ cells freshly isolated from non-immunized mice express at rest significantly higher levels of mRNA for T-helper lineage-specific cytokines IFN-, (Th1), IL-4/IL-10 (Th2), IL-17A/F (Th17), as well as pro-inflammatory cytokines, and rapidly secrete these cytokines upon stimulation. Moreover, the presence of Foxp3,CD39+ cells inhibits TGF-, induction of Foxp3 in Foxp3,CD39, cells. Furthermore, when transferred in vivo, Foxp3,CD39+ cells rejected MHC-mismatched skin allografts in a much faster tempo than Foxp3,CD39, cells. Thus, besides Tregs, CD39 is also expressed on pre-existing memory T cells of Th1-, Th2- and Th17-types with heightened alloreactivity. [source]

    Anomalies in the Oversight of Australian Auditors

    Graeme L. Wines
    This commentary identifies and comments on anomalies in the oversight of Australian auditors and audit firms. Regulatory and professional oversight and inspection of Australian auditors and audit firms arise from a number of sources, highlighting its multi-faceted nature. This makes it impossible to identify a single body with ultimate responsibility for auditor oversight. Three recent Australian reviews commissioned by the Financial Reporting Council, together with an evaluation of the roles of the various regulatory and professional bodies, are used in this commentary as a platform from which to identify a number of significant anomalies in oversight processes. Major anomalies highlighted arise from the overlapping nature of the duties and functions of the various bodies and the variation in oversight across different categories of audit service providers. Policymakers should closely examine the issues raised in the paper if auditor oversight is to be undertaken in an effective and efficient manner. [source]

    Current guidelines applicable for the approval of topically applied dermatological drugs in the EU

    Myrjam Dorothea Straube
    Abstract Dermatologicals as well as other medicinal products are submitted to the rules governing medicinal products in the European Union (EU) (Directive 2001/83/EC). With appreciation of the EU enlargement those regulatories deserve a recent consideration with special regard to the peculiarities of external dermatological therapy, recently passed novel and future guidelines. As regards the criteria for authorization of a medicinal product it is set out in Regulation (EEC) 2309/93 Article 11(1) that a marketing authorization shall be refused if it appears that the quality, the safety or efficacy of the medicinal product have not been adequately or sufficiently demonstrated by the applicant. Article 26(1) of Council Directive 2001/83/EC is worded a little differently but the criteria are the same irrespective of the procedure for the marketing authorization. For the final evaluation of the benefit/risk profile of a topically applied dermatological medicinal product not only the active agent but the whole galenic formulation as well has to be taken into account as the extent of penetration of the active compound might be influenced by changing the non-active substances. Furthermore the vehicle itself , independent of the active agent , influence the dermatological disorder, often in dependence on the stage of the dermatopathy. With special concern to safety/tolerability the (photo)toxic and (photo)allergic potential of the dermatological drug have to be taken into consideration too. In case of total body therapy in children the differing percutaneous resorption due to another body surface/body weight relation deserves special concern. The following review gives a survey of the current most important EU-guidelines for the evaluation of the benefit/risk profile of topically applied dermatological medicinal drugs and an outlook on further developments. As systemically applied dermatological medicinal products are assessed like other systemically applied drugs they are not treated in the following contribution. [source]

    BNP Consensus Panel 2004: A Clinical Approach for the Diagnostic, Prognostic, Screening, Treatment Monitoring, and Therapeutic Roles of Natriuretic Peptides in Cardiovascular Diseases

    Marc A. Silver MD
    Among the most exciting developments in the field of heart failure in recent times has been the rediscovery of the natriuretic peptide system and its pleuripotent effects on cardiac structure and function. This is particularly true of its natriuretic and hemodynamic effects. There has been an explosion of the knowledge base seeking to understand the wide range of homeostatic, regulatory, and counter-regulatory functions in which the natriuretic peptide system participates. Additional interest has been stimulated by advances in technology such as point-of-care and core laboratory BNP assays and the use of the recombinant B-type natriuretic peptide nesiritide as a treatment option. Despite this recent interest, the available literature lacks a comprehensive expert review of the current science and roles of natriuretic peptides for diagnostic, prognostic, screening, treatment monitoring, and therapeutic purposes. More importantly, a summary updating and guiding the clinician on most of these advances was lacking. An expert Consensus Panel with basic, methodological, and clinical expertise was convened to summarize current knowledge in these areas and the findings and consensus statements are contained herein. [source]

    Thyroid hormone receptor , can control action potential duration in mouse ventricular myocytes through the KCNE1 ion channel subunit

    ACTA PHYSIOLOGICA, Issue 2 2010
    A. Mansén
    Abstract Aims:, The reduced heart rate and prolonged QTend duration in mice deficient in thyroid hormone receptor (TR) ,1 may involve aberrant expression of the K+ channel ,-subunit KCNQ1 and its regulatory ,-subunit KCNE1. Here we focus on KCNE1 and study whether increased KCNE1 expression can explain changes in cardiac function observed in TR,1-deficient mice. Methods:, TR-deficient, KCNE1-overexpressing and their respective wildtype (wt) mice were used. mRNA and protein expression were assessed with Northern and Western blot respectively. Telemetry was used to record electrocardiogram and temperature in freely moving mice. Patch-clamp was used to measure action potentials (APs) in isolated cardiomyocytes and ion currents in Chinese hamster ovary (CHO) cells. Results:, KCNE1 was four to 10-fold overexpressed in mice deficient in TR,1. Overexpression of KCNE1 with a heart-specific promoter in transgenic mice resulted in a cardiac phenotype similar to that in TR,1-deficient mice, including a lower heart rate and prolonged QTend time. Cardiomyocytes from KCNE1-overexpressing mice displayed increased AP duration. CHO cells transfected with expression plasmids for KCNQ1 and KCNE1 showed an outward rectifying current that was maximal at equimolar plasmids for KCNQ1-KCNE1 and decreased at higher KCNE1 levels. Conclusion:, The bradycardia and prolonged QTend time in hypothyroid states can be explained by altered K+ channel function due to decreased TR,1-dependent repression of KCNE1 expression. [source]

    Market Consequences of Earnings Management in Response to Security Regulations in China,

    Abstract Under the 1996-98 security regulations in China, the accounting rate of return on equity (ROE) has to be greater than 10 percent for three "consecutive" years for a firm to qualify for stock rights offers. Despite declining economic conditions during this period, the percentage of firms reporting ROE between 10 and 11 percent is about "three" times that for 1994-95. This unique regulatory environment provides a natural experimental setting for the empirical assessment of earnings-management behavior and its consequences. This study examines whether listed Chinese firms manage earnings to meet regulatory benchmarks and whether regulators and investors consider the quality of earnings in their respective regulatory and investment decisions. On the basis of a sample of listed Chinese firms from 1996 to 1998, we observe that managers execute transactions involving below-the-line items and use income-increasing accounting accruals to meet regulatory ROE targets for stock rights offerings. The firms that apply for, but fail to receive, regulatory approval manage earnings more significantly than do firms that receive approval and pair-matched control firms. Our market study also suggests that investors differentiate the quality of earnings and put less value on earnings suspected of a greater degree of management. Overall, our results imply that the regulatory bodies and investors to some extent make rational adjustments for the quality of earnings. [source]

    AMP-activated protein kinase: a core signalling pathway in the heart

    ACTA PHYSIOLOGICA, Issue 1 2009
    A. S. Kim
    Abstract Over the past decade, AMP-activated protein kinase (AMPK) has emerged as an important intracellular signalling pathway in the heart. Activated AMPK stimulates the production of ATP by regulating key steps in both glucose and fatty acid metabolism. It has an inhibitory effect on cardiac protein synthesis. AMPK also interacts with additional intracellular signalling pathways in a coordinated network that modulates essential cellular processes in the heart. Evidence is accumulating that AMPK may protect the heart from ischaemic injury and limit the development of cardiac myocyte hypertrophy to various stimuli. Heart AMPK is activated by hormones, cytokines and oral hypoglycaemic drugs that are used in the treatment of type 2 diabetes. The tumour suppressor LKB1 is the major regulator of AMPK activity, but additional upstream kinases and protein phosphatases also contribute. Mutations in the regulatory ,2 subunit of AMPK lead to an inherited syndrome of hypertrophic cardiomyopathy and ventricular pre-excitation, which appears to be due to intracellular glycogen accumulation. Future research promises to elucidate the molecular mechanisms responsible for AMPK activation, novel downstream AMPK targets, and the therapeutic potential of targeting AMPK for the prevention and treatment of myocardial ischaemia or cardiac hypertrophy. [source]


    Research Summary: The question of whether the illegal firearms market serving criminals and juveniles can be disrupted has been vigorously debated in policy circles and in the literature on firearms and violence. To the extent that prohibited persons, in particular, are supplied with guns through systematic gun trafficking, focused regulatory and investigative resources may be useful in disrupting the illegal supply of firearms to criminals. In Boston, a gun market disruption strategy was implemented that focused on shutting down illegal diversions of new handguns from retail sources. Multivariate regression analyses were used to estimate the effects of the intervention on new handguns recovered in crime. Our results suggest that focused enforcement efforts, guided by strategic analyses of ATF firearms trace data, can have significant impacts on the illegal supply of new handguns to criminals. Policy Implications: The problem-oriented policing approach provides an appropriate framework to uncover the complex mechanisms at play in illicit firearms markets and to develop tailor-made interventions to disrupt the illegal gun trade. Strategic enforcement programs focused on the illegal diversion of new firearms from primary markets can reduce the availability of new guns to criminals. However, the extent to which criminals substitute older guns for new guns and move from primary markets to secondary markets in response to an enforcement strategy focused on retail outlets remains unclear. Our evaluation also does not provide policy makers with any firm evidence on whether supply-side enforcement strategies have any measurable impacts on gun violence. Jurisdictions suffering from gun violence problems should implement demand-side violence prevention programs to complement their supply-side efforts. [source]

    Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidants

    ACTA PHYSIOLOGICA, Issue 4 2007
    M. P. Koeners
    Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source]

    AKAP-independent localization of type-II protein kinase A to dynamic actin microspikes

    CYTOSKELETON, Issue 9 2009
    Robert L. Rivard
    Abstract Regulation of the cyclic AMP-dependent protein kinase (PKA) in subcellular space is required for cytoskeletal dynamics and chemotaxis. Currently, spatial regulation of PKA is thought to require the association of PKA regulatory (R) subunits with A-kinase anchoring proteins (AKAPs). Here, we show that the regulatory RII, subunit of PKA associates with dynamic actin microspikes in an AKAP-independent manner. Both endogenous RII, and a GFP-RII, fusion protein co-localize with F-actin in microspikes within hippocampal neuron growth cones and the leading edge lamellae of NG108-15 cells. Live-cell imaging demonstrates that RII,-associated microspikes are highly dynamic and that the coupling of RII, to actin is tight, as the movement of both actin and RII, are immediately and coincidently stopped by low-dose cytochalasin D. Importantly, co-localization of RII, and actin in these structures is resistant to displacement by a cell-permeable disrupter of PKA-AKAP interactions. Biochemical fractionation confirms that a substantial pool of PKA RII, is associated with the detergent-insoluble cytoskeleton and is resistant to extraction by a peptide inhibitor of AKAP interactions. Finally, mutation of the AKAP-binding domain of RII, fails to disrupt its association with actin microspikes. These data provide the first demonstration of the physical association of a kinase with such dynamic actin structures, as well as the first demonstration of the ability of type-II PKA to localize to discrete subcellular structures independently of canonical AKAP function. This association is likely to be important for microfilament dynamics and cell migration and may prime the investigation of novel mechanisms for localizing PKA activity. Cell Motil. Cytoskeleton 2009. © 2009 Wiley-Liss, Inc. [source]

    Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction,

    CYTOSKELETON, Issue 7 2008
    Amy E. Hanlon Newell
    Abstract A-kinase anchoring proteins (AKAPs) bind to protein kinase A (PKA) via an amphipathic helix domain that interacts with a dimerization/docking domain on the regulatory (R) subunit of PKA. Four other mammalian proteins (ROPN1, ASP, SP17, and CABYR) also contain a highly conserved RII dimerization/docking (R2D2) domain, suggesting all four proteins may interact with all AKAPs in a manner similar to RII. All four of these proteins were originally detected in the flagellum of mammalian sperm. In this report, we demonstrate that all four R2D2 proteins are expressed in a wide variety of tissues and three of the proteins SP17, CABYR, and ASP are located in motile cilia of human bronchus and fallopian tubes. In addition, we detect SP17 in primary cilia. We also provide evidence that ROPN1 and ASP bind to a variety of AKAPs and this interaction can be disrupted with anchoring inhibitor peptides. The interaction of SP17 and CABYR with AKAPs appears to be much more limited. None of the R2D2 proteins appears to bind cAMP, a fundamental characteristic of the regulatory subunits of PKA. These observations suggest that R2D2 proteins utilize docking interactions with AKAPs to accomplish their function of regulating cilia and flagella. Based on location, affinity for AKAPs and lack of affinity for cAMP, it appears that each R2D2 protein has a unique role in this process. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source]

    The Regulatory State and Turkish Banking Reforms in the Age of Post-Washington Consensus

    Caner Bakir
    ABSTRACT The new era of the Post-Washington Consensus (PWC), promoted under the auspices of International Financial Institutions such as the International Monetary Fund and the World Bank, centres on the need to develop sound financial regulation and strong regulatory institutions, especially in the realm of banking and finance in post-financial crisis developing countries. This article uses an examination of the Turkish banking sector experience with the PWC in the aftermath of the 2001 financial crisis to show its considerable strengths and weaknesses. The authors argue that the emergent regulatory state in the bank-based financial system has a narrow focus on strengthening prudential regulation, whilst ignoring the increased ,financialization' of the Turkish economy. They identify the positive features of the new era of the PWC in terms of prudential regulation, which has become much more robust in its ability to withstand external shocks. At the same time, however, the article highlights some of the limitations of the new era which resemble the limitations of the PWC. These include the distributional impact of the regulatory reforms within the banking sector, and notably the emergence of foreign banks as the major beneficiaries of this process; weaknesses in promoting productive bank intermediation that finance the real economy and economic growth, leading to poverty reduction via growth of employment whilst stimulating financialization within the economy; and finally, the exclusive focus on prudential regulation, whilst ignoring regulatory costs, consumer protection and competition regulation. [source]

    Activator of G-protein signaling in asymmetric cell divisions of the sea urchin embryo

    Ekaterina Voronina
    An asymmetric fourth cell division in the sea urchin embryo results in formation of daughter cells, macromeres and micromeres, with distinct sizes and fates. Several lines of functional evidence presented here, including pharmacological interference and dominant negative protein expression, indicate that heterotrimeric G protein Gi and its interaction partner, activator of G-protein signaling (AGS), are necessary for this asymmetric cell division. Inhibition of Gi signaling by pertussis toxin interferes with micromere formation and leads to defects in embryogenesis. AGS was isolated in a yeast two-hybrid screen with G,i as bait and was expressed in embryos localized to the cell cortex at the time of asymmetric divisions. Introduction of exogenous dominant-negative AGS protein, containing only G-protein regulatory (GPR) domains, selectively prevented the asymmetric division in normal micromere formation. These results support the growing evidence that AGS is a universal regulator of asymmetric cell divisions in embryos. [source]

    The Tol2kit: A multisite gateway-based construction kit for Tol2 transposon transgenesis constructs

    Kristen M. Kwan
    Abstract Transgenesis is an important tool for assessing gene function. In zebrafish, transgenesis has suffered from three problems: the labor of building complex expression constructs using conventional subcloning; low transgenesis efficiency, leading to mosaicism in transient transgenics and infrequent germline incorporation; and difficulty in identifying germline integrations unless using a fluorescent marker transgene. The Tol2kit system uses site-specific recombination-based cloning (multisite Gateway technology) to allow quick, modular assembly of [promoter],[coding sequence],[3, tag] constructs in a Tol2 transposon backbone. It includes a destination vector with a cmlc2:EGFP (enhanced green fluorescent protein) transgenesis marker and a variety of widely useful entry clones, including hsp70 and beta-actin promoters; cytoplasmic, nuclear, and membrane-localized fluorescent proteins; and internal ribosome entry sequence,driven EGFP cassettes for bicistronic expression. The Tol2kit greatly facilitates zebrafish transgenesis, simplifies the sharing of clones, and enables large-scale projects testing the functions of libraries of regulatory or coding sequences. Developmental Dynamics 236:3088,3099, 2007. © 2007 Wiley-Liss, Inc. [source]


    Gary Banks Chairman
    The paper examines the existing scope and role of regulations in Australia. While there are many benefits from regulation, there is also a myriad of, often underplayed, costs associated with regulations. While compliance costs are large, probably the most significant costs arise from behavioural responses to regulations that reduce efficiency or compromise social goals. These adverse effects are often unanticipated and arise from complex interactions between regulations. The main reasons for regulatory failure are excessive ambition (underestimating the deficiencies of the regulatory ,solution'), capture of regulatory agencies, and poor regulatory processes and institutions. The paper offers some guidelines for producing better regulation. [source]

    Capital quality improvement and the sources of economic growth in the euro area

    ECONOMIC POLICY, Issue 42 2005
    Plutarchos Sakellaris
    SUMMARY Capital quality improvement and Euroland growth Sources of growth Europe's growth slowed in the 1990s, reinforcing the overall impression of a need to catch up with the US regarding standards of living. In reaction, EU leaders adopted the famous Lisbon Agenda in 2000. The Agenda is now under review, the aim being to determine why progress on its pro-growth goals has been unsatisfactory and what can be done about it. The first crucial step in this process is to understand the true sources of the European growth slowdown. Sources-of-growth calculations have always been imprecise, but evidence from the US suggests that ,quality upgrading', especially in capital goods , has substantially worsened the precision problem since the 1990s. Unfortunately, quality adjusted sources-of-growth calculations, however, have not performed satisfactorily for Europe, so Europe's leaders are working with potentially misleading accounts of Europe's growth slowdown. Redressing this omission is the goal of this paper. Failure to account properly for capital quality improvements leads to two mistakes. First, overall GDP is underestimated. Our calculations, for example, show that euro area GDP growth was underestimated on average by 0.7 percentage points annually in the late 1990s. However, similar quality-adjustment figures raise US growth figures in the same period by even more, so quality-adjusting suggests that the US,EU growth gap was even more pronounced than previously believed. Secondly, the sources-of-growth calculations used to prioritize Europe's pro-growth policies are skewed. Our calculations show that the contribution of the slowdown in disembodied technical progress to the overall slowdown is more pronounced after quality adjustment. Our findings point to the need for adoption of microeconomic measures aimed at enhancing overall efficiency and boosting innovation activity. Such measures would aim at a better business environment, e.g. by easing regulatory and administrative burden and liberalizing energy and telecommunications markets. , Plutarchos Sakellaris and Focco Vijselaar [source]

    Regulation, productivity and growth: OECD evidence

    ECONOMIC POLICY, Issue 36 2003
    Giuseppe Nicoletti
    SUMMARY Liberalization and privatization have made the regulatory environment more market-friendly throughout the OECD. However using a large new dataset on product market regulation, we show that regulatory policies in OECD nations have become more dissimilar in relative terms, even as all nations have liberalized. This seemingly contradictory finding is explained by different starting points and different reform speeds. Our data also show that this divergence in the regulatory settings lines up with the divergent growth performance of OECD nations, in particular the poor performance of large Continental economies relative to that of the US. The data, which tracks various types of product market regulation in manufacturing and service industries for 18 OECD economies over the past two decades, allows us to explore this link in detail. We find that productivity growth is boosted by reforms that promote private corporate governance and competition (where these are viable). Moreover, our detailed findings suggest how product market regulation and productivity growth are linked. In manufacturing, the productivity gains from liberalization are greater the further a given country is from the technology leader. This indicates that entry-limiting regulation may hinder the adoption of existing technologies, possibly by reducing competitive pressures, technology spillovers, or the entry of new high-tech firms. These results offer an interpretation of poor Continental performance. Strict product market regulations , and lack of regulatory reforms , appear to underlie the meagre productivity performance of some European countries, especially in those industries where Europe has accumulated a technology gap (e.g. industries producing or using information and communication technologies). , Giuseppe Nicoletti and Stefano Scarpetta [source]

    A review of potential methods of determining critical effect size for designing environmental monitoring programs,

    Kelly R. Munkittrick
    Abstract The effective design of field studies requires that sample size requirements be estimated for important endpoints before conducting assessments. This a priori calculation of sample size requires initial estimates for the variability of the endpoints of interest, decisions regarding significance levels and the power desired, and identification of an effect size to be detected. Although many programs have called for use of critical effect sizes (CES) in the design of monitoring programs, few attempts have been made to define them. This paper reviews approaches that have been or could be used to set specific CES. The ideal method for setting CES would be to define the level of protection that prevents ecologically relevant impacts and to set a warning level of change that would be more sensitive than that CES level to provide a margin of safety; however, few examples of this approach being applied exist. Program-specific CES could be developed through the use of numbers based on regulatory or detection limits, a number defined through stakeholder negotiation, estimates of the ranges of reference data, or calculation from the distribution of data using frequency plots or multivariate techniques. The CES that have been defined often are consistent with a CES of approximately 25%, or two standard deviations, for many biological or ecological monitoring endpoints, and this value appears to be reasonable for use in a wide variety of monitoring programs and with a wide variety of endpoints. [source]

    Mouse Th17 cells: Current understanding of their generation and regulation

    Chen Dong
    Abstract IL-17-expressing CD4+ T cells have been recently recognized as a new subset of Th cells, namely Th17 cells. Considerable progress has been made in understanding the developmental regulation of mouse Th17 cells. Here, I summarize this knowledge and discuss on the relationship of Th17 with regulatory and follicular Th cells. [source]

    Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells

    Frank Schmitz
    Abstract The mammalian target of rapamycin (mTOR) can be viewed as cellular master complex scoring cellular vitality and stress. Whether mTOR controls also innate immune-defenses is currently unknown. Here we demonstrate that TLR activate mTOR via phosphoinositide 3-kinase/Akt. mTOR physically associates with the MyD88 scaffold protein to allow activation of interferon regulatory factor-5 and interferon regulatory factor-7, known as master transcription factors for pro-inflammatory cytokine- and type I IFN-genes. Unexpectedly, inactivation of mTOR did not prevent but increased lethality of endotoxin-mediated shock, which correlated with increased levels of IL-1,. Mechanistically, mTOR suppresses caspase-1 activation, thus inhibits release of bioactive IL-1,. We have identified mTOR as indispensable component of PRR signal pathways, which orchestrates the defense program of innate immune cells. [source]