Regulatory Processes (regulatory + process)

Distribution by Scientific Domains
Distribution within Life Sciences


Selected Abstracts


Regulatory processes interacting to maintain hepatic blood flow constancy: Vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction

HEPATOLOGY RESEARCH, Issue 11 2007
W. Wayne Lautt
Constancy of hepatic blood flow (HBF) is crucial for several homeostatic roles. The present conceptual review focuses on interrelated mechanisms that act to maintain a constant HBF per liver mass. The liver cannot directly control portal blood flow (PF); therefore, these mechanisms largely operate to compensate for PF changes. A reduction in PF leads to reduced intrahepatic distending pressure, resulting in the highly compliant hepatic vasculature passively expelling up to 50% of its blood volume, thus adding to venous return, cardiac output and HBF. Also activated immediately upon reduction of PF are the hepatic arterial buffer response and an HBF-dependent hepatorenal reflex. Adenosine is secreted at a constant rate into the small fluid space of Mall which surrounds the terminal branches of the hepatic arterioles, portal venules and sensory nerves. The concentration of adenosine is regulated by washout into the portal venules. Reduced PFreduces the washout and the accumulated adenosine causes dilation of the hepatic artery, thus buffering the PF change. Adenosine also activates hepatic sensory nerves to cause reflex renal fluid retention, thus increasing circulating blood volume and maintaining cardiac output and PF. If these mechanisms are not able to maintain total HBF, the hemodynamic imbalance results in hepatocyte proliferation, or apoptosis, by a shear stress/nitric oxide-dependent mechanism, to adjust total liver mass to match the blood supply. These mechanisms are specific to this unique vascular bed and provide an excellent example of multiple integrative regulation of a major homeostatic organ. [source]


Physiological effects of separation and reunion in relation to attachment and temperament in young children

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2007
Mirjam Oosterman
Abstract This study examined physiological effects of separation and reunion in a sample 3- to 6-year-old children. Using continuous ambulatory recording, changes in heart rate (HR), respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) were compared across the episodes of a separation,reunion procedure based on the strange situation. RSA decreased significantly over the course of the procedure as well as on separation from the parent and not the stranger, supporting that separation from the attachment figure elicited vagal withdrawal in young children. The absence of significant PEP effects suggest that the separation,reunion procedure, and more specifically separation from the parent, was not threatening enough to activate the sympathetic nervous system, even if children were insecure attached and inhibited with regard to strangers. Some of the variability in HR increases to reunion was explained by younger age. The findings highlight the role of the ANS as a regulatory process in the parent,child relationship. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 119,128, 2007. [source]


Towards a Semiology of the Periodic Review of UK Regulated Utilities

FINANCIAL ACCOUNTABILITY & MANAGEMENT, Issue 3 2001
Stuart Cooper
This note explores the regulatory process of UK privatised utilities through the periodic review of prices. It provides a brief history of the privatisation programme in the UK and the theoretical arguments for the price-cap regulation that has been used. It argues that regulatory process appears to involve a covert dialogue and exchange of information between the regulator and regulated and also a second separate review process that consists of an overt dialogue. Using a semiotic analysis the authors suggest that the unfolding of each of these overt reviews follows a very similar pattern that is constantly being re-enacted. It is concluded that further research is required into the relative importance of the two separate review processes in the setting of the price-cap. [source]


Political Cost Incentives for Managing the Property-Liability Insurer Loss Reserve

JOURNAL OF ACCOUNTING RESEARCH, Issue 1 2010
MARTIN F. GRACE
ABSTRACT This paper examines the effect of rate regulation on the management of the property-liability insurer loss reserve. The political cost hypothesis predicts that managers make accounting choices to reduce wealth transfers resulting from the regulatory process. Managers may under-state reserves to justify lower rates to regulators. Alternatively, managers may have an incentive to report loss inflating discretionary reserves to reduce the cost of regulatory rate suppression. We find insurers over-state reserves in the presence of stringent rate regulation. Investigating the impact along the conditional reserve error distribution, we discover that a majority of the response occurs from under-reserving firms under-reserving less because of stringent rate regulation. [source]


If bone is the answer, then what is the question?

JOURNAL OF ANATOMY, Issue 2 2000
R. HUISKES
In the 19th century, several scientists attempted to relate bone trabecular morphology to its mechanical, load-bearing function. It was suggested that bone architecture was an answer to requirements of optimal stress transfer, pairing maximal strength to minimal weight, according to particular mathematical design rules. Using contemporary methods of analysis, stress transfer in bones was studied and compared with anatomical specimens, from which it was hypothesised that trabecular architecture is associated with stress trajectories. Others focused on the biological processes by which trabecular architectures are formed and on the question of how bone could maintain the relationship between external load and architecture in a variable functional environment. Wilhelm Roux introduced the principle of functional adaptation as a self-organising process based in the tissues. Julius Wolff, anatomist and orthopaedic surgeon, entwined these 3 issues in his book The Law of Bone Remodeling (translation), which set the stage for biomechanical research goals in our day. ,Wolff's Law' is a question rather than a law, asking for the requirements of structural optimisation. In this article, based on finite element analysis (FEA) results of stress transfer in bones, it is argued that it was the wrong question, putting us on the wrong foot. The maximal strength/minimal weight principle does not provide a rationale for architectural formation or adaptation; the similarity between trabecular orientation and stress trajectories is circumstantial, not causal. Based on computer simulations of bone remodelling as a regulatory process, governed by mechanical usage and orchestrated by osteocyte mechanosensitivity, it is shown that Roux's paradigm, conversely, is a realistic proposition. Put in a quantitative regulatory context, it can predict both trabecular formation and adaptation. Hence, trabecular architecture is not an answer to Wolff's question, in the sense of this article's title. There are no mathematical optimisation rules for bone architecture; there is just a biological regulatory process, producing a structure adapted to mechanical demands by the nature of its characteristics, adequate for evolutionary endurance. It is predicted that computer simulation of this process can help us to unravel its secrets. [source]


Regulation of mitogen-activated protein kinases by glutamate receptors

JOURNAL OF NEUROCHEMISTRY, Issue 1 2007
John Q. Wang
Abstract Glutamate receptors regulate gene expression in neurons by activating intracellular signaling cascades that phosphorylate transcription factors within the nucleus. The mitogen-activated protein kinase (MAPK) cascade is one of the best characterized cascades in this regulatory process. The Ca2+ -permeable ionotropic glutamate receptor, mainly the NMDA receptor subtype, activates MAPKs through a biochemical route involving the Ca2+ -sensitive Ras-guanine nucleotide releasing factor, Ca2+/calmodulin-dependent protein kinase II, and phosphoinositide 3-kinase. The metabotropic glutamate receptor (mGluR), however, activates MAPKs primarily through a Ca2+ -insensitve pathway involving the transactivation of receptor tyrosine kinases. The adaptor protein Homer also plays a role in this process. As an information superhighway between surface glutamate receptors and transcription factors in the nucleus, active MAPKs phosphorylate specific transcription factors (Elk-1 and CREB), and thereby regulate distinct programs of gene expression. The regulated gene expression contributes to the development of multiple forms of synaptic plasticity related to long-lasting changes in memory function and addictive properties of drugs of abuse. This review, by focusing on new data from recent years, discusses the signaling mechanisms by which different types of glutamate receptors activate MAPKs, features of each MAPK cascade in regulating gene expression, and the importance of glutamate/MAPK-dependent synaptic plasticity in memory and addiction. [source]


Assessing OSHA Performance: New Evidence from the Construction Industry

JOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 4 2001
David Weil
The determinants of OSHA performance can be examined by breaking the regulatory process into three elements relating to enforcement, compliance behavior, and the adequacy of standards in addressing safety outcomes. This paper develops and applies this framework to the U.S. construction industry during the period 1987 to 1993. Enforcement activity among the firms in the sample was substantial, with firms facing a high probability of annual inspection. But, despite this significant enforcement effort, inspections have a modest effect on firm compliance with OSHA standards. Finally, the health and safety standards cited most frequently diverge from the major sources of fatalities and injuries on construction projects. These results suggest that historic enforcement policies toward construction make less sense as OSHA moves into its fourth decade of operation. More generally, the paper illustrates the problem of focusing enforcement resources on large, high‐profile companies even though they often are not the major source of regulatory problems in an established area of public policy intervention. © 2001 by the Association for Public Policy Analysis and Management. [source]


Mss11p is a transcription factor regulating pseudohyphal differentiation, invasive growth and starch metabolism in Saccharomyces cerevisiae in response to nutrient availability

MOLECULAR MICROBIOLOGY, Issue 1 2003
Marco Gagiano
Summary In Saccharomyces cerevisiae, the cell surface protein, Muc1p, was shown to be critical for invasive growth and pseudohyphal differentiation. The transcription of MUC1 and of the co-regulated STA2 glucoamylase gene is controlled by the interplay of a multitude of regulators, including Ste12p, Tec1p, Flo8p, Msn1p and Mss11p. Genetic analysis suggests that Mss11p plays an essential role in this regulatory process and that it functions at the convergence of at least two signalling cascades, the filamentous growth MAPK cascade and the cAMP-PKA pathway. Despite this central role in the control of filamentous growth and starch metabolism, the exact molecular function of Mss11p is unknown. We subjected Mss11p to a detailed molecular analysis and report here on its role in transcriptional regulation, as well as on the identification of specific domains required to confer transcriptional activation in response to nutritional signals. We show that Mss11p contains two independent transactivation domains, one of which is a highly conserved sequence that is found in several proteins with unidentified function in mammalian and invertebrate organisms. We also identify conserved amino acids that are required for the activation function. [source]


Australian food regulations public consultation process: Teaching postgraduate dietetics students to participate

NUTRITION & DIETETICS, Issue 2-3 2005
Shawn Somerset
Abstract Objective:, To assess a teaching strategy to develop competency, familiarity and willingness of dietetic students to participate in food regulation development. Design:, Qualitative evaluation of self-perceived learning outcomes. Subjects/Setting:, Two consecutive cohorts (n = 39) of postgraduate dietetics students from Griffith University. Intervention:, Preparation and presentation of a formal response to a call for comment by Australia's food regulatory body (Food Standards Australia New Zealand) during the period 1999,2001. Main outcome measures:, Self-reported descriptions of confidence, familiarity and willingness to participate in the public consultation process. Results:, Following the assignment, students generally reported being more familiar with the regulatory process and more confident to participate. Most students identified the importance of reference material on Food Standards Australia New Zealand procedures that they could use for review should the opportunity for participation arise at a later date. A major issue identified was the potential for cynicism towards the process. This issue was seen as a potential barrier to participation by students after graduation. Applications/Conclusions:, This issues-based approach to teaching of a food regulation system has potential to enhance participation in regulatory development by a broader cross-section of dietitians. [source]


Incidents of bee poisoning with pesticides in the United Kingdom, 1994,2003

PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 11 2007
Elizabeth A Barnett
Abstract For over 20 years, the UK Agriculture Departments have monitored the direct effects of pesticides on beneficial insects, mainly honeybees (Apis mellifera, L.) and bumblebees (Bombus terrestris, L.), as part of the Wildlife Incident Investigation Scheme (WIIS). The Central Science Laboratory (CSL) has contributed to WIIS by providing the required laboratory skills for the determination of bee diseases and the expert analytical experience necessary to determine low-level pesticide residues and interpret these results. The results from WIIS form part of the pesticide regulatory process coordinated by the Pesticides Safety Directorate (PSD) and are published each year. This paper has reviewed the data from WIIS over the 10 year period from 1994 to 2003. The overall trend is that suspected poisoning incidents, reported by beekeepers and the general public, have declined from 56 incidents per year to 23 incidents per year. The number of these incidents that have been attributed to pesticide poisoning has also declined, from 25 incidents to five incidents per year. The possible reasons for these changes and the circumstances involved in the bee poisoning incidents are discussed. However, the source of the pesticide in bee poisoning incidents is often uncertain and the likely cause of these incidents and any trends over time are also discussed. © Crown copyright 2007. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd. [source]


The New Bureaucracies of Virtue or When Form Fails to Follow Function

POLAR: POLITICAL AND LEGAL ANTHROPOLOGY REVIEW, Issue 2 2007
Charles L. Bosk
As the prospective review of research protocols has expanded to include ethnography, researchers have responded with a mixture of bewilderment, irritation, and formal complaint. These responses typically center on how poorly a process modeled on the randomized clinical trial fits the realities of the more dynamic, evolving methods that are used to conduct ethnographic research. However warranted these complaints are, those voicing them have not analyzed adequately the logic in use that allowed the system of review to extend with so little resistance. This paper locates the expansion in the goal displacement that Merton identified as part of bureaucratic organization and identifies the tensions between researchers and administrators as a consequence of an inversion of the normal status hierarchy found in universities. Social scientists need to do more than complain about the regulatory process; they also need to make that apparatus an object for study. Only recently have social scientists taken up the task in earnest. This paper contributes to emerging efforts to understand how prospective review of research protocols presents challenges to ethnographers and how ethnographic proposals do the same for IRBs (Institutional Research Boards). This essay extends three themes that are already prominent in the literature discussing IRBs and ethnography: (1) the separation of bureaucratic regulations,policies,and procedures from the everyday questions of research ethics that are most likely to trouble ethnographers; (2) the goal displacement that occurs when the entire domain of research ethics is reduced to compliance with a set of federal regulations as interpreted by local committees; and (3) the difficulties of sense making when ethnographers and IRB administrators or panel members respond each to the other's concerns. [source]


How does activation loop phosphorylation modulate catalytic activity in the cAMP-dependent protein kinase: A theoretical study

PROTEIN SCIENCE, Issue 4 2006
Yuhui Cheng
Abstract Phosphorylation mediates the function of many proteins and enzymes. In the catalytic subunit of cAMP-dependent protein kinase, phosphorylation of Thr 197 in the activation loop strongly influences its catalytic activity. In order to provide theoretical understanding about this important regulatory process, classical molecular dynamics simulations and ab initio QM/MM calculations have been carried out on the wild-type PKA,Mg2 ATP,substrate complex and its dephosphorylated mutant, T197A. It was found that pThr 197 not only facilitates the phosphoryl transfer reaction by stabilizing the transition state through electrostatic interactions but also strongly affects its essential protein dynamics as well as the active site conformation. [source]


Evading Enron: Taking Principles Too Seriously In Accounting Regulation

THE MODERN LAW REVIEW, Issue 4 2005
Article first published online: 1 JUL 200, David Kershaw
The UK's regulators and accounting profession are at one in their assessment of why the UK avoided its Enron: the UK's approach to accounting regulation is principles-based in contrast to the rules-based approach taken in the United States. According to this position, the UK has its principles-based regulatory technique to thank for keeping the integrity of its markets intact during the infectious greed of the 1990s. This article is an inquiry into the effect and validity of this claim. It investigates the effect that this claim has had upon structuring the UK's post-Enron regulatory process and provides a close analysis of UK and US accounting regulation to determine whether the UK's regulation is in fact distinctively principles-based. It concludes that the structuring effect of the claim was considerable, diverting the reform process away from some of the US's most important Enron lessons. This is of particular concern as the article also concludes that the claim is without foundation. [source]


Lessons from Environmental Regulation for the Nonprofit Sector

ANNALS OF PUBLIC AND COOPERATIVE ECONOMICS, Issue 3 2002
Renee A. Irvin
As the third sector's economic and social impact grows worldwide, efforts by governments to regulate the sector have focused on increasing compliance in tax,exempt organizations. This article turns to the environmental sector for guidance, summarizing key characteristics of environmental regulation and noting what strategies are likely to prove useful for application to regulation of nonprofit organizations. The article finds some value in promotion of market,based enforcement schemes, but little value in promulgation of laws specifying governance structures and performance standards by a central authority. The most promising opportunity for improvement of the nonprofit regulatory process involves incorporation of financial incentives into monitoring schemes. [source]


Regulatory hurdles for transgenic biofuel crops

BIOFUELS, BIOPRODUCTS AND BIOREFINING, Issue 4 2009
David Lee
Abstract Policy-makers have described the many potential benefits that biofuels can provide, but there are numerous challenges in realizing this potential. The technical hurdles to producing biofuels economically and on a scale to replace a significant fraction of petroleum-based transportation fuels have been well described, along with the potential environmental concerns. The use of biotechnology can potentially address many of these technical challenges and environmental concerns, but brings significant regulatory obstacles that have not been discussed extensively in the scientific community. This review will give an overview of some of the approaches being developed to produce transgenic biofuel feedstocks, particularly cellulosic ethanol, and the regulatory process in the United States that oversees the introduction of new transgenic plants. We hope to illustrate that the level of regulation for transgenic organisms is not proportional to their potential risk to human health or to the environment, and that while revisions to the regulatory system in the USA are currently under consideration, further modifications are necessary to reflect the risk level of transgenic crops and realize their benefits. © 2009 Society of Chemical Industry and John Wiley & Sons, Ltd [source]


Choosing strategic responses to address emerging environmental regulations: size, perceived influence and uncertainty

BUSINESS STRATEGY AND THE ENVIRONMENT, Issue 8 2008
Bruce Clemens
Abstract How companies respond to impending regulations is a significant aspect of corporate strategy. Regulations, especially environmental regulations, are expanding quickly and increasingly important to firm success. The threat of impending environmental regulation forces companies to choose levels of strategic responses on a continuum from passive to active. Using practitioner oriented research and existing theoretical models of corporate response, this study finds that the type of strategic response is negatively related to size, positively related to state uncertainty and negatively related to effect/response uncertainty. Based on existing literature and the results of this study, the paper suggests that simplifying the uncertainty construct could lead to more definitive findings in future research. The study results also suggest that a curvilinear relationship may exist between managerial perception of influence and level of strategic response. Most importantly, the findings could have a significant impact on firm decision making regarding environmental investments. For example, it is hoped that firms will be able to use the findings of this study to further understand and anticipate their competitors' decisions. Practitioners may also benefit from the conclusions on uncertainty in that they may be able to more cleanly parse the types of uncertainty immersed in impending environmental regulations. Finally, firms may be better able to understand decisions by their own managers and their competitors' managers in terms of their perceived influence over the regulatory process. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment. [source]


Variation in Pesticide Tolerance of Tadpoles among and within Species of Ranidae and Patterns of Amphibian Decline

CONSERVATION BIOLOGY, Issue 5 2000
Christine M. Bridges
Because variability exists among organisms in their sensitivity to environmental stressors, it is important to determine the degree of this variation when undertaking conservation efforts. We conducted both lethal (time-to-death) and sublethal (activity change) assays to determine the degree of variation in the sensitivity of tadpoles to a pesticide, carbaryl, at three hierarchical levels: among ranid species, among several populations of a single ranid species ( Rana sphenocephala), and within populations of R. sphenocephala. We observed significant variation in time to death among the nine ranid species and among the 10 R. sphenocephala populations we tested. Four out of eight R. sphenocephala populations exhibited significantly different times to death among families. The magnitude of the activity change in response to exposure to sublethal carbaryl levels was significantly different among species and within R. sphenocephala populations. Chemical contamination, at lethal or sublethal levels, can alter natural regulatory processes such as juvenile recruitment in amphibian populations and should be considered a contributing cause of declines in amphibian populations. Resumen: Existe una variación significativa entre y dentro de especies de anfibios con respecto a los reportes de disminuciones poblacionales; las especies en disminución son frecuentemente encontradas en ambientes que son fisiográficamente similares a ambientes donde las mismas especies están prosperando. Debido a que la variabilidad existe entre organismos en lo referente a su sensibilidad a estresores ambientales, es importante determinar el grado de esta variación cuando se lleven a cabo esfuerzos de conservación. Nosotros llevamos a cabo ensayos tanto letales (tiempo de muerte) como subletales (cambios de actividad) para determinar el grado de variación en la sensibilidad de renacuajos a un pesticida, carbaryl, en tres niveles jerárquicos: entre especies de ránidos, entre diversas poblaciones de una sola especie de ránido ( Rana sphenocephala) y dentro de poblaciones de R. sphenocephala. Observamos diferencias significativas en tiempo de muerte entre las nueve especies de ránidos y entre las 10 poblaciones de R. sphenocephala evaluadas. Cuatro de ocho poblaciones de R. sphenocephala exhibieron tiempos de muerte significativamente diferentes entre familias. La magnitud del cambio de actividad al ser expuestas a niveles subletales de carbaryl fue significativamente diferente entre especies y dentro de poblaciones de R. sphenocephala. La contaminación química, a niveles letales y subletales, puede alterar los procesos reguladores naturales (por ejemplo el reclutamiento de juveniles) en poblaciones de anfibios y debería ser considerado como una causa que contribuye a la disminución de poblaciones de anfibios. [source]


Cells of all somitic compartments are determined with respect to segmental identity

DEVELOPMENTAL DYNAMICS, Issue 4 2005
Marlyse Dieuguie Fomenou
Abstract Development of somite cells is orchestrated by two regulatory processes. Differentiation of cells from the various somitic compartments into different anlagen and tissues is regulated by extrinsic signals from neighboring structures such as the notochord, neural tube, and surface ectoderm. Morphogenesis of these anlagen to form specific structures according to the segmental identity of each somite is specified by segment-specific positional information, based on the Hox -code. It has been shown that following experimental rotation of presomitic mesoderm or newly formed somites, paraxial mesodermal cells adapt to the altered signaling environment and differentiate according to their new orientation. In contrast, presomitic mesoderm or newly formed somites transplanted to different segmental levels keep their primordial segmental identity and form ectopic structures according to their original position. To determine whether all cells of a segment, including the dorsal and ventral compartment, share the same segmental identity, presomitic mesoderm or newly formed somites were rotated and transplanted from thoracic to cervical level. These experiments show that cells from all compartments of a segment are able to interpret extrinsic local signals correctly, but form structures according to their original positional information and maintain their original Hox expression in the new environment. Developmental Dynamics 233:1386,1393, 2005. © 2005 Wiley-Liss, Inc. [source]


THE GOOD, THE BAD AND THE UGLY: ECONOMIC PERSPECTIVES ON REGULATION IN AUSTRALIA

ECONOMIC PAPERS: A JOURNAL OF APPLIED ECONOMICS AND POLICY, Issue 1 2004
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]


Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and , -melanocyte-stimulating hormone in the skin

EXPERIMENTAL DERMATOLOGY, Issue 10 2006
Simone König
Abstract:, The neuroendocrine precursor protein proopiomelanocortin (POMC) and its derived neuropeptides are involved in a number of important regulatory processes in the central nervous system as well as in peripheral tissues. Despite its important role in controlling the local activation of melanocortin (MC) receptors, the extracellular proteolytic processing of POMC peptides has received little attention. The mechanisms relevant for controlling the bioavailability of adrenocorticotropin and melanocyte-stimulating hormones for the corresponding MC receptors in the skin by specific peptidases such as neprilysin (neutral endopeptidase; NEP) or angiotensin-converting enzyme (ACE) have been addressed in a number of recent investigations. This review summarizes the current body of knowledge concerning the qualitative and quantitative POMC peptide processing with respect to the action and specificity of NEP and ACE and discusses relevant recent analytical methodologies. [source]


Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index

EXPERIMENTAL DERMATOLOGY, Issue 8 2006
Heike Schäcke
Abstract:, Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor- ,B or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands. [source]


Governing Standards: The Rise of Standardization Processes in France and in the EU

GOVERNANCE, Issue 1 2007
OLIVIER BORRAZ
The rise of standardization processes highlights two different paths toward a regulatory state. Within the EU, the New Approach serves as a model for co-regulation, and European standards have become instruments of supranational governance. In France, standardization is much more part of a renegotiation of the state's role and influence in a changing society. In both cases, standardization was undertaken with other motives; yet it evolved to answer the strains and constraints exerted upon regulatory processes in the two polities. As such, standards are a case for unintentionality in policy instruments. [source]


HuR regulates gap junctional intercellular communication by controlling ,-catenin levels and adherens junction integrity,

HEPATOLOGY, Issue 5 2009
Niloofar Ale-Agha
Gap junctional intercellular communication (GJIC) plays a critical role in the regulation of tissue homeostasis and carcinogenesis and is modulated by the levels, subcellular localization, and posttranslational modification of gap junction proteins, the connexins (Cx). Here, using oval cell-like rat liver epithelial cells, we demonstrate that the RNA-binding protein HuR promotes GJIC through two mechanisms. First, HuR silencing lowered the levels of Cx43 protein and Cx43 messenger RNA (mRNA), and decreased Cx43 mRNA half-life. This regulation was likely due to the direct stabilization of Cx43 mRNA by HuR, because HuR associated directly with Cx43 mRNA, a transcript that bears signature adenylate-uridylate-rich (AU-rich) and uridylate-rich (U-rich) sequences in its 3,-untranslated region. Second, HuR silencing reduced both half-life and the levels of ,-catenin mRNA, also a target of HuR; accordingly, HuR silencing lowered the levels of whole-cell and membrane-associated ,-catenin. Coimmunoprecipitation experiments showed a direct interaction between ,-catenin and Cx43. Small interfering RNA (siRNA)-mediated depletion of ,-catenin recapitulated the effects of decreasing HuR levels: it attenuated GJIC, decreased Cx43 levels, and redistributed Cx43 to the cytoplasm, suggesting that depletion of ,-catenin in HuR-silenced cells contributed to lowering Cx43 levels at the membrane. Finally, HuR was demonstrated to support GJIC after exposure to a genotoxic agent, doxorubicin, or an inducer of differentiation processes, retinoic acid, thus pointing to a crucial role of HuR in the cellular response to stress and in physiological processes modulated by GJIC. Conclusion: HuR promotes gap junctional intercellular communication in rat liver epithelial cells through two related regulatory processes, by enhancing the expression of Cx43 and by increasing the expression of ,-catenin, which, in turn, interacts with Cx43 and is required for proper positioning of Cx43 at the plasma membrane. (HEPATOLOGY 2009.) [source]


Application of multicriteria decision analysis in environmental decision making

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 2 2005
Gregory A. Kiker
Abstract Decision making in environmental projects can be complex and seemingly intractable, principally because of the inherent trade-offs between sociopolitical, environmental, ecological, and economic factors. The selection of appropriate remedial and abatement strategies for contaminated sites, land use planning, and regulatory processes often involves multiple additional criteria such as the distribution of costs and benefits, environmental impacts for different populations, safety, ecological risk, or human values. Some of these criteria cannot be easily condensed into a monetary value, partly because environmental concerns often involve ethical and moral principles that may not be related to any economic use or value. Furthermore, even if it were possible to aggregate multiple criteria rankings into a common unit, this approach would not always be desirable because the ability to track conflicting stakeholder preferences may be lost in the process. Consequently, selecting from among many different alternatives often involves making trade-offs that fail to satisfy 1 or more stakeholder groups. Nevertheless, considerable research in the area of multicriteria decision analysis (MCDA) has made available practical methods for applying scientific decision theoretical approaches to complex multicriteria problems. This paper presents a review of the available literature and provides recommendations for applying MCDA techniques in environmental projects. A generalized framework for decision analysis is proposed to highlight the fundamental ingredients for more structured and tractable environmental decision making. [source]


Setting the rules: private power, political underpinnings, and legitimacy in global monetary and financial governance

INTERNATIONAL AFFAIRS, Issue 3 2008
GEOFFREY R. D. UNDERHILL
The role of private market agents in global monetary and financial governance has increased as globalization has proceeded. This shift in both markets and patterns of governance has often been encouraged by states themselves in pursuit of liberalization policies. Much of the literature views these developments in a positive light, yet there are other aspects of these developments that also merit attention. This article supports its central propositions with two cases of emerging global financial governance processes: the Basel II capital adequacy standards for international banking supervision and the International Organization of Securities Commissions-based transnational regulatory processes underpinning the functioning of cross-border securities markets. Based on the case findings, the article argues first that private sector self-regulation and/or public-private partnership in governance processes can leave public authorities vulnerable to dependence on the information and expertise provided by private agents in a fast-moving market environment. Policy in the vital domain of financial regulation has been increasingly aligned to private sector preferences to a degree that should raise fears of bureaucratic capture. Second, the article contends that the overall outcome in terms of global financial system efficiency and stability has been mixed, bringing a range of important benefits but also instability and crisis for many societies to a degree that has led to challenges to global governance itself. The case material indicates that the input, output and accountability phases of legitimacy in global monetary and financial governance are highly problematic, and much of the problem relates to the way in which private market agents are integrated into the decision-making process. Third, the article posits that a better consideration of these three ,phases' of legitimacy and their interrelationships is likely to enhance the political underpinnings and legitimacy of global financial and monetary order. [source]


Overcompensatory population dynamic responses to environmental stochasticity

JOURNAL OF ANIMAL ECOLOGY, Issue 6 2008
James C. Bull
Summary 1To quantify the interactions between density-dependent, population regulation and density-independent limitation, we studied the time-series dynamics of an experimental laboratory insect microcosm system in which both environmental noise and resource limitation were manipulated. 2A hierarchical Bayesian state-space approach is presented through which it is feasible to capture all sources of uncertainty, including observation error to accurately quantify the density dependence operating on the dynamics. 3The regulatory processes underpinning the dynamics of two different bruchid beetles (Callosobruchus maculatus and Callosobruchus chinensis) are principally determined by environmental conditions, with fluctuations in abundance explained in terms of changes in overcompensatory dynamics and stochastic processes. 4A general, stochastic population model is developed to explore the link between abundance fluctuations and the interaction between density dependence and noise. Taking account of time-lags in population regulation can substantially increase predicted population fluctuations resulting from underlying noise processes. [source]


Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf

AGING CELL, Issue 5 2009
Riva P. Oliveira
Summary Studies in model organisms have identified regulatory processes that profoundly influence aging, many of which modulate resistance against environmental or metabolic stresses. In Caenorhabditis elegans, the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways. SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2 detoxification genes in response to stress. Phase 2 enzymes defend against oxygen radicals and conjugate electrophiles that are produced by Phase 1 detoxification enzymes, which metabolize lipophilic compounds. Here, we have used expression profiling to identify genes and processes that are regulated by SKN-1 under normal and stress,response conditions. Under nonstressed conditions SKN-1 upregulates numerous genes involved in detoxification, cellular repair, and other functions, and downregulates a set of genes that reduce stress resistance and lifespan. Many of these genes appear to be direct SKN-1 targets, based upon presence of predicted SKN-binding sites in their promoters. The metalloid sodium arsenite induces skn-1- dependent activation of certain detoxification gene groups, including some that were not SKN-1-upregulated under normal conditions. An organic peroxide also triggers induction of a discrete Phase 2 gene set, but additionally stimulates a broad SKN-1-independent response. We conclude that under normal conditions SKN-1 has a wide range of functions in detoxification and other processes, including modulating mechanisms that reduce lifespan. In response to stress, SKN-1 and other regulators tailor transcription programs to meet the challenge at hand. Our findings reveal striking complexity in SKN-1 functions and the regulation of systemic detoxification defenses. [source]


Flk prevents premature secretion of the anti-, factor FlgM into the periplasm

MOLECULAR MICROBIOLOGY, Issue 3 2006
Phillip Aldridge
Summary The flk locus of Salmonella typhimurium was identified as a regulator of flagellar gene expression in strains defective in P- and l -ring formation. Flk acts as a regulator of flagellar gene expression by modulating the protein levels of the anti-,28 factor FlgM. Evidence is presented which suggests that Flk is a cytoplasmic-facing protein anchored to the inner membrane by a single, C-terminal transmembrane-spanning domain (TMS). The specific amino acid sequence of the TMS is not essential for Flk activity, but membrane anchoring is essential. Membrane fractionation and visualization of protein fusions of green fluorescent protein derivatives to Flk suggested that the Flk protein is present in the membrane as punctate spots in number that are much greater than the number of flagellar basal structures. The turnover of the anti-,28 factor FlgM was increased in flk mutant strains. Using FlgM,,-lactamase fusions we show the increased turnover of FlgM in flk null mutations is due to FlgM secretion into the periplasm where it is degraded. Our data suggest that Flk inhibits FlgM secretion by acting as a braking system for the flagellar-associated type III secretion system. A model is presented to explain a role for Flk in flagellar assembly and gene regulatory processes. [source]


Apical callus formation and plant regeneration controlled by plant growth regulators on axenic culture of the red alga Gracilariopsis tenuifrons (Gracilariales, Rhodophyta)

PHYCOLOGICAL RESEARCH, Issue 3 2000
Nair S. Yokoya
SUMMARY Axenic cultures of Gracilariopsis tenuifrons (Bird et Oliveira) Fredericq et Hommersand (Gracilariales, Rhodophyta) were established in ASP12-NTA solid medium (0.4% agar and 1.0% sucrose) supplemented with plant growth regulators to evaluate the effects on apical callus formation and plant regeneration. Indole-3-acetic acid (IAA), 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BA) were added individually or in combinations (IAA : BA) over a range of concentrations from 0.5 to 5 mg L,1. Growth of apical and intercalary segments was stimulated by high concentrations of 2,4-D (5 mg L,1) and a high IAA to BA ratio (IAA : BA = 5:1 mg L,1) respectively. Apical calluses were originated from divisions of apical and cortical cells located at apical regions of thallus segments and lateral branches. Low concentration of IAA (0.5 mg L,1) or a high IAA to BA ratio (IAA : BA = 5:1 mg L,1) were the optimal treatments for inducing apical callus formation in apical segments, while high concentration of IAA (5 mg L,1) stimulated the highest callus induction rate in intercalary segments. Conversely, equal parts IAA and BA (IAA : BA = 1:1 mg L,1) and low concentration of 2,4-D (0.5 mg L,1) stimulated growth of apical calluses from apical and intercalary segments, respectively. Two processes of regeneration were observed: direct regeneration (upright axis originated from cells of proximal region of intercalary segments) and indirect regeneration (adventitious plantlet originated from cells of apical calluses). Direct regeneration was promoted significantly by treatment with a low IAA to BA ratio (IAA : BA= 1:5 mg L,1), and treatments with IAA (0.5 mgL,1) or 2,4-D (0.5 or 5 mg L,1) significantly stimulated the elongation of upright axis. Plant growth regulators are essential to inducing indirect regeneration, and a high concentration of IAA (5 mg L,1) and BA (5 mg L,1) were the optimal treatments for inducing the regeneration of plantlets from apical calluses in apical and intercalary segments, respectively. Regenerating plantlets grew into plants morphologically similar to those formed from germinating spores, and became fertile after 6 weeks. The results suggest that auxins and cytokinins are involved in developmental regulatory processes in G. tenuifrons. The regeneration process from calluses in species of Gracilariales was observed for the first time in the present study. The culture system described for G. tenuifrons could be useful for micropropagation and for biotechnological applications in agarophytic algae. [source]


The Nature of Exocytosis in the Yolk Trophoblastic Layer of Silver Arowana (Osteoglossum bicirrhosum) Juvenile, the Representative of Ancient Teleost Fishes

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 11 2009
Marta Jaroszewska
Abstract We have chosen the silver arowana (Osteoglossum bicirrhosum), a representative of the most ancient teleost family Osteoglossidae, to address the question of yolk nutrients utilization. Silver arowana have particularly large eggs (1,1.5 cm of diameter) and a unique morphology of the yolk. We present evidence that the yolk cytoplasmic zone (ycz) in the "yolksac juveniles" is a very complex structure involved in sequential processes of yolk hydrolysis, lipoprotein particles synthesis, their transport, and exocytosis. Vacuoles filled with yolk granules in different stages of digestion move from the vitellolysis zone through the ycz to be emptied into the microvillar interspace in the process of exocytosis. The area of the ycz with the abundance of the mitochondria must play an important role in providing energy for both the transport of vacuoles and the release of their contents. Therefore, we postulate that the function of yolk syncytial layer (ysl) as the "early embryonic patterning center" transforms in fish larvae or yolksac juveniles into a predominantly specialized role as the yolk trophoblastic layer (ytl) involved in yolk nutrients utilization. In addition to discovering the mechanism of transformation of the ysl function into ytl function, we suggest that the machinery involved in nutrient mobilization and exocytosis in yolk of arowana yolksac juveniles can be very attractive system for studies of regulatory processes in almost all secretory pathways in animal cells. Anat Rec, 2009. © 2009 Wiley-Liss, Inc. [source]