Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies.

Science.gov (United States)

Rudomanova, Valeria; Blaxall, Burns C

2017-08-01

The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

GPCR-SSFE: A comprehensive database of G-protein-coupled receptor template predictions and homology models

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Kreuchwig Annika

2011-05-01

Full Text Available Abstract Background G protein-coupled receptors (GPCRs transduce a wide variety of extracellular signals to within the cell and therefore have a key role in regulating cell activity and physiological function. GPCR malfunction is responsible for a wide range of diseases including cancer, diabetes and hyperthyroidism and a large proportion of drugs on the market target these receptors. The three dimensional structure of GPCRs is important for elucidating the molecular mechanisms underlying these diseases and for performing structure-based drug design. Although structural data are restricted to only a handful of GPCRs, homology models can be used as a proxy for those receptors not having crystal structures. However, many researchers working on GPCRs are not experienced homology modellers and are therefore unable to benefit from the information that can be gleaned from such three-dimensional models. Here, we present a comprehensive database called the GPCR-SSFE, which provides initial homology models of the transmembrane helices for a large variety of family A GPCRs. Description Extending on our previous theoretical work, we have developed an automated pipeline for GPCR homology modelling and applied it to a large set of family A GPCR sequences. Our pipeline is a fragment-based approach that exploits available family A crystal structures. The GPCR-SSFE database stores the template predictions, sequence alignments, identified sequence and structure motifs and homology models for 5025 family A GPCRs. Users are able to browse the GPCR dataset according to their pharmacological classification or search for results using a UniProt entry name. It is also possible for a user to submit a GPCR sequence that is not contained in the database for analysis and homology model building. The models can be viewed using a Jmol applet and are also available for download along with the alignments. Conclusions The data provided by GPCR-SSFE are useful for investigating

GPCR-SSFE: a comprehensive database of G-protein-coupled receptor template predictions and homology models.

Science.gov (United States)

Worth, Catherine L; Kreuchwig, Annika; Kleinau, Gunnar; Krause, Gerd

2011-05-23

G protein-coupled receptors (GPCRs) transduce a wide variety of extracellular signals to within the cell and therefore have a key role in regulating cell activity and physiological function. GPCR malfunction is responsible for a wide range of diseases including cancer, diabetes and hyperthyroidism and a large proportion of drugs on the market target these receptors. The three dimensional structure of GPCRs is important for elucidating the molecular mechanisms underlying these diseases and for performing structure-based drug design. Although structural data are restricted to only a handful of GPCRs, homology models can be used as a proxy for those receptors not having crystal structures. However, many researchers working on GPCRs are not experienced homology modellers and are therefore unable to benefit from the information that can be gleaned from such three-dimensional models. Here, we present a comprehensive database called the GPCR-SSFE, which provides initial homology models of the transmembrane helices for a large variety of family A GPCRs. Extending on our previous theoretical work, we have developed an automated pipeline for GPCR homology modelling and applied it to a large set of family A GPCR sequences. Our pipeline is a fragment-based approach that exploits available family A crystal structures. The GPCR-SSFE database stores the template predictions, sequence alignments, identified sequence and structure motifs and homology models for 5025 family A GPCRs. Users are able to browse the GPCR dataset according to their pharmacological classification or search for results using a UniProt entry name. It is also possible for a user to submit a GPCR sequence that is not contained in the database for analysis and homology model building. The models can be viewed using a Jmol applet and are also available for download along with the alignments. The data provided by GPCR-SSFE are useful for investigating general and detailed sequence-structure-function relationships

Onco-GPCR signaling and dysregulated expression of microRNAs in human cancer.

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Nohata, Nijiro; Goto, Yusuke; Gutkind, J Silvio

2017-01-01

The G-protein-coupled receptor (GPCR) family is the largest family of cell-surface receptors involved in signal transduction. Aberrant expression of GPCRs and G proteins are frequently associated with prevalent human diseases, including cancer. In fact, GPCRs represent the therapeutic targets of more than a quarter of the clinical drugs currently on the market. MiRNAs (miRNAs) are also aberrantly expressed in many human cancers, and they have significant roles in the initiation, development and metastasis of human malignancies. Recent studies have revealed that dysregulation of miRNAs and their target genes expression are associated with cancer progression. The emerging information suggests that miRNAs play an important role in the fine tuning of many signaling pathways, including GPCR signaling. We summarize our current knowledge of the individual functions of miRNAs regulated by GPCRs and GPCR signaling-associated molecules, and miRNAs that regulate the expression and activity of GPCRs, their endogenous ligands and their coupled heterotrimeric G proteins in human cancer.

Color-pattern analysis of eyespots in butterfly wings: a critical examination of morphogen gradient models.

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Otaki, Joji M

2011-06-01

Butterfly wing color patterns consist of many color-pattern elements such as eyespots. It is believed that eyespot patterns are determined by a concentration gradient of a single morphogen species released by diffusion from the prospective eyespot focus in conjunction with multiple thresholds in signal-receiving cells. As alternatives to this single-morphogen model, more flexible multiple-morphogen model and induction model can be proposed. However, the relevance of these conceptual models to actual eyespots has not been examined systematically. Here, representative eyespots from nymphalid butterflies were analyzed morphologically to determine if they are consistent with these models. Measurement of ring widths of serial eyespots from a single wing surface showed that the proportion of each ring in an eyespot is quite different among homologous rings of serial eyespots of different sizes. In asymmetric eyespots, each ring is distorted to varying degrees. In extreme cases, only a portion of rings is expressed remotely from the focus. Similarly, there are many eyespots where only certain rings are deleted, added, or expanded. In an unusual case, the central area of an eyespot is composed of multiple "miniature eyespots," but the overall macroscopic eyespot structure is maintained. These results indicate that each eyespot ring has independence and flexibility to a certain degree, which is less consistent with the single-morphogen model. Considering a "periodic eyespot", which has repeats of a set of rings, damage-induced eyespots in mutants, and a scale-size distribution pattern in an eyespot, the induction model is the least incompatible with the actual eyespot diversity.

G protein-coupled receptor transmembrane binding pockets and their applications in GPCR research and drug discovery: a survey.

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Kratochwil, Nicole A; Gatti-McArthur, Silvia; Hoener, Marius C; Lindemann, Lothar; Christ, Andreas D; Green, Luke G; Guba, Wolfgang; Martin, Rainer E; Malherbe, Pari; Porter, Richard H P; Slack, Jay P; Winnig, Marcel; Dehmlow, Henrietta; Grether, Uwe; Hertel, Cornelia; Narquizian, Robert; Panousis, Constantinos G; Kolczewski, Sabine; Steward, Lucinda

2011-01-01

G protein-coupled receptors (GPCRs) share a common architecture consisting of seven transmembrane (TM) domains. Various lines of evidence suggest that this fold provides a generic binding pocket within the TM region for hosting agonists, antagonists, and allosteric modulators. Hence, an automated method was developed that allows a fast analysis and comparison of these generic ligand binding pockets across the entire GPCR family by providing the relevant information for all GPCRs in the same format. This methodology compiles amino acids lining the TM binding pocket including parts of the ECL2 loop in a so-called 1D ligand binding pocket vector and translates these 1D vectors in a second step into 3D receptor pharmacophore models. It aims to support various aspects of GPCR drug discovery in the pharmaceutical industry. Applications of pharmacophore similarity analysis of these 1D LPVs include definition of receptor subfamilies, prediction of species differences within subfamilies in regard to in vitro pharmacology and identification of nearest neighbors for GPCRs of interest to generate starting points for GPCR lead identification programs. These aspects of GPCR research are exemplified in the field of melanopsins, trace amine-associated receptors and somatostatin receptor subtype 5. In addition, it is demonstrated how 3D pharmacophore models of the LPVs can support the prediction of amino acids involved in ligand recognition, the understanding of mutational data in a 3D context and the elucidation of binding modes for GPCR ligands and their evaluation. Furthermore, guidance through 3D receptor pharmacophore modeling for the synthesis of subtype-specific GPCR ligands will be reported. Illustrative examples are taken from the GPCR family class C, metabotropic glutamate receptors 1 and 5 and sweet taste receptors, and from the GPCR class A, e.g. nicotinic acid and 5-hydroxytryptamine 5A receptor. © 2011 Bentham Science Publishers

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

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Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

2013-04-30

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

iGPCR-drug: a web server for predicting interaction between GPCRs and drugs in cellular networking.

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Xuan Xiao

Full Text Available Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called "iGPCR-drug", was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug - target interaction networks.

MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR.

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Krause, Claudia J; Popp, Oliver; Thirunarayanan, Nanthakumar; Dittmar, Gunnar; Lipp, Martin; Müller, Gerd

2016-03-01

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.

The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity.

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Wang, Dashan

2018-06-01

The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and β-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. GPCR signaling plays an important role in T cell activation, homeostasis and function. GPCR signaling is critical in regulating T cell immunity.

Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

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Page, Karen M.

2016-01-01

During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

FLIPR assays of intracellular calcium in GPCR drug discovery

DEFF Research Database (Denmark)

Hansen, Kasper Bø; Bräuner-Osborne, Hans

2009-01-01

Fluorescent dyes sensitive to changes in intracellular calcium have become increasingly popular in G protein-coupled receptor (GPCR) drug discovery for several reasons. First of all, the assays using the dyes are easy to perform and are of low cost compared to other assays. Second, most non...

GPCR-SSFE 2.0-a fragment-based molecular modeling web tool for Class A G-protein coupled receptors.

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Worth, Catherine L; Kreuchwig, Franziska; Tiemann, Johanna K S; Kreuchwig, Annika; Ritschel, Michele; Kleinau, Gunnar; Hildebrand, Peter W; Krause, Gerd

2017-07-03

G-protein coupled receptors (GPCRs) are key players in signal transduction and therefore a large proportion of pharmaceutical drugs target these receptors. Structural data of GPCRs are sparse yet important for elucidating the molecular basis of GPCR-related diseases and for performing structure-based drug design. To ameliorate this problem, GPCR-SSFE 2.0 (http://www.ssfa-7tmr.de/ssfe2/), an intuitive web server dedicated to providing three-dimensional Class A GPCR homology models has been developed. The updated web server includes 27 inactive template structures and incorporates various new functionalities. Uniquely, it uses a fingerprint correlation scoring strategy for identifying the optimal templates, which we demonstrate captures structural features that sequence similarity alone is unable to do. Template selection is carried out separately for each helix, allowing both single-template models and fragment-based models to be built. Additionally, GPCR-SSFE 2.0 stores a comprehensive set of pre-calculated and downloadable homology models and also incorporates interactive loop modeling using the tool SL2, allowing knowledge-based input by the user to guide the selection process. For visual analysis, the NGL viewer is embedded into the result pages. Finally, blind-testing using two recently published structures shows that GPCR-SSFE 2.0 performs comparably or better than other state-of-the art GPCR modeling web servers. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Agronomic, morphogenic and structural characteristics of Marandu grass in silvopastoral systems composed of babassu palm and grass monoculture

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Rosane Cláudia Rodrigues

2016-09-01

Full Text Available This study evaluated the agronomic, morphogenic and structural characteristics of palisadegrass (Urochloa brizantha in silvopastoral systems (SSP’s composed of babassu palms (Attalea speciosa and grass monoculture in the Pre-Amazon region of the state of Maranhão, Brazil. The study followed a completely randomized design, with the arrangement in split plots with six replicates for the evaluation of agronomic characteristics and 30 repetitions for the morphogenic and structural characteristics. The plots were divided into pasture environments with different palm densities (monoculture, 80, 131, 160 palms.ha-¹, and the subplots were divided into the different seasons (rainy and dry. Total forage production was affected (P 0.05 by pastoral system during the rainy season, but in the dry period, higher responses were obtained in SSPs. Overall, SSPs with 80 palms.ha-¹ favored the agronomic characteristics of pastures. Morphogenic and structural characteristics were favored by increasing palm densities. Leaf senescence and duration were not affected by the system.

Trends in GPCR drug discovery: new agents, targets and indications

DEFF Research Database (Denmark)

Hauser, Alexander Sebastian; Gloriam, David E.; Attwood, Misty M.

2017-01-01

current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially...... are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug......G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals...

Multiplexed profiling of GPCR activities by combining split TEV assays and EXT-based barcoded readouts.

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Galinski, Sabrina; Wichert, Sven P; Rossner, Moritz J; Wehr, Michael C

2018-05-25

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and are implicated in the physiological regulation of many biological processes. The high diversity of GPCRs and their physiological functions make them primary targets for therapeutic drugs. For the generation of novel compounds, however, selectivity towards a given target is a critical issue in drug development as structural similarities between members of GPCR subfamilies exist. Therefore, the activities of multiple GPCRs that are both closely and distantly related to assess compound selectivity need to be tested simultaneously. Here, we present a cell-based multiplexed GPCR activity assay, termed GPCRprofiler, which uses a β-arrestin recruitment strategy and combines split TEV protein-protein interaction and EXT-based barcode technologies. This approach enables simultaneous measurements of receptor activities of multiple GPCR-ligand combinations by applying massively parallelized reporter assays. In proof-of-principle experiments covering 19 different GPCRs, both the specificity of endogenous agonists and the polypharmacological effects of two known antipsychotics on GPCR activities were demonstrated. Technically, normalization of barcode reporters across individual assays allows quantitative pharmacological assays in a parallelized manner. In summary, the GPCRprofiler technique constitutes a flexible and scalable approach, which enables simultaneous profiling of compound actions on multiple receptor activities in living cells.

High Content Analysis of Compositional Heterogeneities to Study GPCR Oligomerization

DEFF Research Database (Denmark)

Walsh, Samuel McEwen

In this thesis I demonstrate how the natural compositional heterogeneities of synthetic and living cell model systems can be used to quantitate the mechanics of G-protein coupled receptor (GPCR) oligomerization with Förster resonance energy transfer (FRET). The thesis is structured around three a...

Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma.

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Teoh, Chun Ming; Tam, John Kit Chung; Tran, Thai

2012-01-01

Airway hyperresponsiveness (AHR) is one of the cardinal features of asthma. Contraction of airway smooth muscle (ASM) cells that line the airway wall is thought to influence aspects of AHR, resulting in excessive narrowing or occlusion of the airway. ASM contraction is primarily controlled by agonists that bind G protein-coupled receptor (GPCR), which are expressed on ASM. Integrins also play a role in regulating ASM contraction signaling. As therapies for asthma are based on symptom relief, better understanding of the crosstalk between GPCRs and integrins holds good promise for the design of more effective therapies that target the underlying cellular and molecular mechanism that governs AHR. In this paper, we will review current knowledge about integrins and GPCRs in their regulation of ASM contraction signaling and discuss the emerging concept of crosstalk between the two and the implication of this crosstalk on the development of agents that target AHR.

Membrane-mediated oligomerization of G protein coupled receptors and its implications for GPCR function

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Stefan Gahbauer

2016-10-01

Full Text Available The dimerization or even oligomerization of G protein coupled receptors (GPCRs causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signalling complexes. Recent findings further suggest that the surrounding membrane, i.e. its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.

Efficient silkworm expression of human GPCR (nociceptin receptor) by a Bombyx mori bacmid DNA system

International Nuclear Information System (INIS)

Kajikawa, Mizuho; Sasaki, Kaori; Wakimoto, Yoshitaro; Toyooka, Masaru; Motohashi, Tomoko; Shimojima, Tsukasa; Takeda, Shigeki; Park, Enoch Y.; Maenaka, Katsumi

2009-01-01

Guanine nucleotide-binding protein (G protein) coupled receptors (GPCRs) are frequently expressed by a baculovirus expression vector system (BEVS). We recently established a novel BEVS using the bacmid system of Bombyx mori nucleopolyhedrovirus (BmNPV), which is directly applicable for protein expression in silkworms. Here, we report the first example of GPCR expression in silkworms by the simple injection of BmNPV bacmid DNA. Human nociceptin receptor, an inhibitory GPCR, and its fusion protein with inhibitory G protein alpha subunit (G i α) were both successfully expressed in the fat bodies of silkworm larvae as well as in the BmNPV viral fraction. Its yield was much higher than that from Sf9 cells. The microsomal fractions including the nociceptin receptor fusion, which are easily prepared by only centrifugation steps, exhibited [ 35 S]GTPγS-binding activity upon specific stimulation by nociceptin. Therefore, this rapid method is easy-to-use and has a high expression level, and thus will be an important tool for human GPCR production.

Quantification of GPCR internalization by single-molecule microscopy in living cells.

NARCIS (Netherlands)

Serge, A.; Keijzer, S. de; Hemert, F. Van; Hickman, M.R.; Hereld, D.; Spaink, H.P.; Schmidt, T.; Snaar-Jagalska, B.E.

2011-01-01

Receptor internalization upon ligand stimulation is a key component of a cell's response and allows a cell to correctly sense its environment. Novel fluorescent methods have enabled the direct visualization of the agonist-stimulated G-protein-coupled receptors (GPCR) trafficking in living cells.

Efficient silkworm expression of human GPCR (nociceptin receptor) by a Bombyx mori bacmid DNA system

Energy Technology Data Exchange (ETDEWEB)

Kajikawa, Mizuho; Sasaki, Kaori [Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Wakimoto, Yoshitaro; Toyooka, Masaru [Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Motohashi, Tomoko; Shimojima, Tsukasa [National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 (Japan); Takeda, Shigeki [Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Park, Enoch Y. [Laboratory of Biotechnology, Integrated Bioscience Section, Graduate School of Science and Technology, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka, Shizuoka 422-8529 (Japan); Maenaka, Katsumi, E-mail: kmaenaka-umin@umin.net [Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2009-07-31

Guanine nucleotide-binding protein (G protein) coupled receptors (GPCRs) are frequently expressed by a baculovirus expression vector system (BEVS). We recently established a novel BEVS using the bacmid system of Bombyx mori nucleopolyhedrovirus (BmNPV), which is directly applicable for protein expression in silkworms. Here, we report the first example of GPCR expression in silkworms by the simple injection of BmNPV bacmid DNA. Human nociceptin receptor, an inhibitory GPCR, and its fusion protein with inhibitory G protein alpha subunit (G{sub i}{alpha}) were both successfully expressed in the fat bodies of silkworm larvae as well as in the BmNPV viral fraction. Its yield was much higher than that from Sf9 cells. The microsomal fractions including the nociceptin receptor fusion, which are easily prepared by only centrifugation steps, exhibited [{sup 35}S]GTP{gamma}S-binding activity upon specific stimulation by nociceptin. Therefore, this rapid method is easy-to-use and has a high expression level, and thus will be an important tool for human GPCR production.

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

International Nuclear Information System (INIS)

Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

2008-01-01

A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/- ) versus wild type (AChE +/+ ) mice indicated that while these OPs inhibited axonal growth in AChE +/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

The current state of GPCR-based drug discovery to treat metabolic disease.

Science.gov (United States)

Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

2018-02-02

One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

Science.gov (United States)

Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

2017-09-01

Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

Pharmacogenomics of GPCR Drug Targets

DEFF Research Database (Denmark)

Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

2018-01-01

Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.

Directory of Open Access Journals (Sweden)

Bruno C Jham

2011-04-01

Full Text Available Kaposi's sarcoma (KS is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF, essential for KS development. However, the origin of VEGF in this tumor remains unclear.Here we report that the KSHV G protein-coupled receptor (vGPCR upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression.Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.

Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings

Directory of Open Access Journals (Sweden)

Otaki Joji M

2012-03-01

Full Text Available Abstract Background To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs based on colour-pattern analysis of the nymphalid butterfly Junonia almana. Results In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. Conclusions In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to

Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings.

Science.gov (United States)

Otaki, Joji M

2012-03-13

To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs) based on colour-pattern analysis of the nymphalid butterfly Junonia almana. In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to butterfly eyespots, delineates a theoretical basis for the

Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.

Science.gov (United States)

Semack, Ansley; Sandhu, Manbir; Malik, Rabia U; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

2016-08-19

Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

DEFF Research Database (Denmark)

Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner

2016-01-01

-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay...

Regulation of GPCR-mediated smooth muscle contraction : implications for asthma and pulmonary hypertension

NARCIS (Netherlands)

Wright, D B; Tripathi, S; Sikarwar, A; Santosh, K T; Perez-Zoghbi, J; Ojo, O O; Irechukwu, N; Ward, J P T; Schaafsma, D

Contractile G-protein-coupled receptors (GPCRs) have emerged as key regulators of smooth muscle contraction, both under healthy and diseased conditions. This brief review will discuss some key topics and novel insights regarding GPCR-mediated airway and vascular smooth muscle contraction as

Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits

Directory of Open Access Journals (Sweden)

Brian S. Muntean

2018-01-01

Full Text Available Summary: Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-protein-coupled receptors (GPCRs that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs integrate neuromodulatory inputs while accommodating diversity of incoming signals is poorly understood. In this study, we develop an in vivo tool and analytical suite for analyzing GPCR responses by monitoring the dynamics of a key second messenger, cyclic AMP (cAMP, with excellent quantitative and spatiotemporal resolution in various neurons. Using this imaging approach in combination with CRISPR/Cas9 editing and optogenetics, we interrogate neuromodulatory mechanisms of defined populations of neurons in an intact mesolimbic reward circuit and describe how individual inputs generate discrete second-messenger signatures in a cell- and receptor-specific fashion. This offers a resource for studying native neuronal GPCR signaling in real time. : Muntean et al. develop an in vivo reagent to study processing of neurotransmitter GPCR signals by monitoring real-time dynamics of cAMP responses. They demonstrate application of this approach, in combination with CRISPR/Cas9 gene editing and optogenetics, to interrogate the functional organization of a striatal circuit. Keywords: cAMP, GPCR, neuromodulation, dopamine, striatum, imaging, optogenetics

Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

Science.gov (United States)

Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

2014-03-01

Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR?

Science.gov (United States)

Illingworth, Christopher J R; Parkes, Kevin E; Snell, Christopher R; Mullineaux, Philip M; Reynolds, Christopher A

2008-03-01

Methods to determine periodicity in protein sequences are useful for inferring function. Fourier transformation is one approach but care is required to ensure the periodicity is genuine. Here we have shown that empirically-derived statistical tables can be used as a measure of significance. Genuine protein sequences data rather than randomly generated sequences were used as the statistical backdrop. The method has been applied to G-protein coupled receptor (GPCR) sequences, by Fourier transformation of hydrophobicity values, codon frequencies and the extent of over-representation of codon pairs; the latter being related to translational step times. Genuine periodicity was observed in the hydrophobicity whereas the apparent periodicity (as inferred from previously reported measures) in the translation step times was not validated statistically. GCR2 has recently been proposed as the plant GPCR receptor for the hormone abscisic acid. It has homology to the Lanthionine synthetase C-like family of proteins, an observation confirmed by fold recognition. Application of the Fourier transform algorithm to the GCR2 family revealed strongly predicted seven fold periodicity in hydrophobicity, suggesting why GCR2 has been reported to be a GPCR, despite negative indications in most transmembrane prediction algorithms. The underlying multiple sequence alignment, also required for the Fourier transform analysis of periodicity, indicated that the hydrophobic regions around the 7 GXXG motifs commence near the C-terminal end of each of the 7 inner helices of the alpha-toroid and continue to the N-terminal region of the helix. The results clearly explain why GCR2 has been understandably but erroneously predicted to be a GPCR.

The systematic annotation of the three main GPCR families in Reactome.

Science.gov (United States)

Jassal, Bijay; Jupe, Steven; Caudy, Michael; Birney, Ewan; Stein, Lincoln; Hermjakob, Henning; D'Eustachio, Peter

2010-07-29

Reactome is an open-source, freely available database of human biological pathways and processes. A major goal of our work is to provide an integrated view of cellular signalling processes that spans from ligand-receptor interactions to molecular readouts at the level of metabolic and transcriptional events. To this end, we have built the first catalogue of all human G protein-coupled receptors (GPCRs) known to bind endogenous or natural ligands. The UniProt database has records for 797 proteins classified as GPCRs and sorted into families A/1, B/2 and C/3 on the basis of amino acid sequence. To these records we have added details from the IUPHAR database and our own manual curation of relevant literature to create reactions in which 563 GPCRs bind ligands and also interact with specific G-proteins to initiate signalling cascades. We believe the remaining 234 GPCRs are true orphans. The Reactome GPCR pathway can be viewed as a detailed interactive diagram and can be exported in many forms. It provides a template for the orthology-based inference of GPCR reactions for diverse model organism species, and can be overlaid with protein-protein interaction and gene expression datasets to facilitate overrepresentation studies and other forms of pathway analysis. Database URL: http://www.reactome.org.

Mutations in the C-terminal region affect subcellular localization of crucian carp herpesvirus (CaHV) GPCR.

Science.gov (United States)

Wang, Jun; Gui, Lang; Chen, Zong-Yan; Zhang, Qi-Ya

2016-08-01

G protein-coupled receptors (GPCRs) are known as seven transmembrane domain receptors and consequently can mediate diverse biological functions via regulation of their subcellular localization. Crucian carp herpesvirus (CaHV) was recently isolated from infected fish with acute gill hemorrhage. CaHV GPCR of 349 amino acids (aa) was identified based on amino acid identity. A series of variants with truncation/deletion/substitution mutation in the C-terminal (aa 315-349) were constructed and expressed in fathead minnow (FHM) cells. The roles of three key C-terminal regions in subcellular localization of CaHV GPCR were determined. Lysine-315 (K-315) directed the aggregation of the protein preferentially at the nuclear side. Predicted N-myristoylation site (GGGWTR, aa 335-340) was responsible for punctate distribution in periplasm or throughout the cytoplasm. Predicted phosphorylation site (SSR, aa 327-329) and GGGWTR together determined the punctate distribution in cytoplasm. Detection of organelles localization by specific markers showed that the protein retaining K-315 colocalized with the Golgi apparatus. These experiments provided first evidence that different mutations of CaHV GPCR C-terminals have different affects on the subcellular localization of fish herpesvirus-encoded GPCRs. The study provided valuable information and new insights into the precise interactions between herpesvirus and fish cells, and could also provide useful targets for antiviral agents in aquaculture.

CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation.

Directory of Open Access Journals (Sweden)

Richard Hunte

2018-04-01

Full Text Available Approximately 12% of all human cancers worldwide are caused by infections with oncogenic viruses. Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8 is one of the oncogenic viruses responsible for human cancers, including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL, and the lymphoproliferative disorder multicentric Castleman's disease (MCD. Chronic inflammation mediated by KSHV infection plays a decisive role in the development and survival of these cancers. NF-κB, a family of transcription factors regulating inflammation, cell survival, and proliferation, is persistently activated in KSHV-infected cells. The KSHV latent and lytic expressing oncogenes involved in NF-κB activation are vFLIP/K13 and vGPCR, respectively. However, the mechanisms by which NF-κB is activated by vFLIP and vGPCR are poorly understood. In this study, we have found that a host molecule, Cell Adhesion Molecule 1 (CADM1, is robustly upregulated in KSHV-infected PBMCs and KSHV-associated PEL cells. Further investigation determined that both vFLIP and vGPCR interacted with CADM1. The PDZ binding motif localized at the carboxyl terminus of CADM1 is essential for both vGPCR and vFLIP to maintain chronic NF-κB activation. Membrane lipid raft associated CADM1 interaction with vFLIP is critical for the initiation of IKK kinase complex and NF-κB activation in the PEL cells. In addition, CADM1 played essential roles in the survival of KSHV-associated PEL cells. These data indicate that CADM1 plays key roles in the activation of NF-κB pathways during latent and lytic phases of the KSHV life cycle and the survival of KSHV-infected cells.

Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist

Directory of Open Access Journals (Sweden)

John D. Chan

2016-12-01

Full Text Available 5-hydroxytryptamine (5-HT is a key regulator of muscle contraction in parasitic flatworms. In Schistosoma mansoni, the myoexcitatory action of 5-HT is effected through activation of a serotonergic GPCR (Sm.5HTRL, prioritizing pharmacological characterization of this target for anthelmintic drug discovery. Here, we have examined the effects of several aporphine alkaloids on the signaling activity of a heterologously expressed Sm.5HTRL construct using a cAMP biosensor assay. Four structurally related natural products – nuciferine, D-glaucine, boldine and bulbocapnine – were demonstrated to block Sm.5HTRL evoked cAMP generation with the potency of GPCR blockade correlating well with the ability of each drug to inhibit contractility of schistosomule larvae. Nuciferine was also effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. These data advance our understanding of structure-affinity relationships at Sm.5HTRL, and demonstrate the effectiveness of Sm.5HTRL antagonists as hypomotility-evoking drugs across different parasite life cycle stages.

F4/80: the macrophage-specific adhesion-GPCR and its role in immunoregulation.

Science.gov (United States)

Lin, Hsi-Hsien; Stacey, Martin; Stein-Streilein, Joan; Gordon, Siamon

2010-01-01

As a macrophage-restricted reagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF-TM7 member of the adhesion-GPCR family, great interest was ignited to understand its cell type-specific expression pattern as well as its functional role in macrophage biology. Recent studies have shown that the F4/80 gene is regulated by a novel set of transcription factors that recognized a unique promoter sequence. Gene targeting experiments have produced two F4/80 knock out animal models and showed that F4/80 is not required for normal macrophage development. Nevertheless, the F4/80 receptor was found to be necessary for the induction of efferent CD8+ regulatory T cells responsible for peripheral immune tolerance. The identification of cellular ligands for F4/80 and delineation of its signaling pathway remain elusive but are critical to understand the in vivo role of this macrophage-specific adhesion-GPCR.

TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

Directory of Open Access Journals (Sweden)

Nadine Kirschmer

Full Text Available The Transient Receptor Potential Channel Subunit 4 (TRPC4 has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II stimulation. NRCs infected with TRPC4β (Ad-C4β also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not

GPCR Mutation information - GRIPDB | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us GRI...s and exposed in molecular surface. Data file File name: gripdb_mutation_info.zip File URL: ftp://ftp.biosciencedbc.jp/archive/gri...pdb/LATEST/gripdb_mutation_info.zip File size: 766 bytes Si...mple search URL http://togodb.biosciencedbc.jp/togodb/view/gripdb_mutation_info#en Data acquisition method P... Site Policy | Contact Us GPCR Mutation information - GRIPDB | LSDB Archive ...

GPCR Interaction - GRIPDB | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us GRI...ed information (disease etc.). Data file File name: gripdb_main.zip File URL: ftp://ftp.biosciencedbc.jp/archive/gripdb/LATEST/gri...godb.biosciencedbc.jp/togodb/view/gripdb_main#en Data acquisition method PDB, Refseq Data analysis method - ...Number of data entries 409 entries Data item Description GRIP ID Interaction ID Main Title Interaction title...tabase Database Description Download License Update History of This Database Site Policy | Contact Us GPCR Interaction - GRIPDB | LSDB Archive ...

Global medicinal chemistry and GPCR conference: interview with Stevan Djuric.

Science.gov (United States)

Djuric, Stevan

2018-04-01

Stevan Djuric speaks to Benjamin Walden, Commissioning Editor. Stevan Djuric is head of the global Medicinal Chemistry Leadership Team at AbbVie and is also Vice President of the Discovery Chemistry and Technology organization within their Discovery organization and chemistry outsourcing activities. He spoke at the Global-Medicinal-Chemistry and GPCR summit on the imperative to develop chemistry related technology that can reduce cycle time, cost of goods and improve probability of success. To this end, he discussed his efforts in the chemistry technology area with a focus on integrated synthesis-purification bioassay, and flow photochemistry and high temperature chemistry platforms.

Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.

Science.gov (United States)

Bénazet, Jean-Denis; Zeller, Rolf

2009-10-01

A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.

Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery

OpenAIRE

Bohn, Laura M.; McDonald, Patricia H.

2010-01-01

G protein-coupled receptors (GPCR) are the major site of action for endogenous hormones and neurotransmitters. Early drug discovery efforts focused on determining whether ligands could engage G protein coupling and subsequently activate or inhibit cognate “second messengers.” Gone are those simple days as we now realize that receptors can also couple βarrestins. As we delve into the complexity of ligand-directed signaling and receptosome scaffolds, we are faced with what may seem like endless...

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

OpenAIRE

Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

2001-01-01

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth fa...

Voice Prosthetic Biofilm Formation and Candida Morphogenic Conversions in Absence and Presence of Different Bacterial Strains and Species on Silicone-Rubber

NARCIS (Netherlands)

van der Mei, Henny C.; Buijssen, Kevin J. D. A.; van der Laan, Bernard F. A. M.; Ovchinnikova, Ekatarina; Geertsema-Doornbusch, Gesinda I.; Atema-Smit, Jelly; van de Belt-Gritter, Betsy; Busscher, Henk J.

2014-01-01

Morphogenic conversion of Candida from a yeast to hyphal morphology plays a pivotal role in the pathogenicity of Candida species. Both Candida albicans and Candida tropicalis, in combination with a variety of different bacterial strains and species, appear in biofilms on silicone-rubber voice

Fighting obesity with a sugar-based library: discovery of novel MCH-1R antagonists by a new computational-VAST approach for exploration of GPCR binding sites.

Science.gov (United States)

Heifetz, Alexander; Barker, Oliver; Verquin, Geraldine; Wimmer, Norbert; Meutermans, Wim; Pal, Sandeep; Law, Richard J; Whittaker, Mark

2013-05-24

Obesity is an increasingly common disease. While antagonism of the melanin-concentrating hormone-1 receptor (MCH-1R) has been widely reported as a promising therapeutic avenue for obesity treatment, no MCH-1R antagonists have reached the market. Discovery and optimization of new chemical matter targeting MCH-1R is hindered by reduced HTS success rates and a lack of structural information about the MCH-1R binding site. X-ray crystallography and NMR, the major experimental sources of structural information, are very slow processes for membrane proteins and are not currently feasible for every GPCR or GPCR-ligand complex. This situation significantly limits the ability of these methods to impact the drug discovery process for GPCR targets in "real-time", and hence, there is an urgent need for other practical and cost-efficient alternatives. We present here a conceptually pioneering approach that integrates GPCR modeling with design, synthesis, and screening of a diverse library of sugar-based compounds from the VAST technology (versatile assembly on stable templates) to provide structural insights on the MCH-1R binding site. This approach creates a cost-efficient new avenue for structure-based drug discovery (SBDD) against GPCR targets. In our work, a primary VAST hit was used to construct a high-quality MCH-1R model. Following model validation, a structure-based virtual screen yielded a 14% hit rate and 10 novel chemotypes of potent MCH-1R antagonists, including EOAI3367472 (IC50 = 131 nM) and EOAI3367474 (IC50 = 213 nM).

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

International Nuclear Information System (INIS)

Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

2002-01-01

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

2002-03-06

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

Effects of Bone Morphogenic Proteins on Engineered Cartilage

Science.gov (United States)

Gooch, Keith, J.; Blunk, Torsten; Courter, Donald L.; Sieminski, Alisha; Vunjak-Novakovic, Gordana; Freed, Lisa E.

2007-01-01

A report describes experiments on the effects of bone morphogenic proteins (BMPs) on engineered cartilage grown in vitro. In the experiments, bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid scaffolds and cultured in, variously, a control medium or a medium supplemented with BMP-2, BMP-12, or BMP-13 in various concentrations. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks macroscopically and histologically resembled native cartilage. At a concentration of 100 ng/mL, BMP-2, BMP-12, or BMP-13 caused (1) total masses of the constructs to exceed those of the controls by 121, 80, or 62 percent, respectively; (2) weight percentages of glycosaminoglycans in the constructs to increase by 27, 18, or 15, respectively; and (3) total collagen contents of the constructs to decrease to 63, 89, or 83 percent of the control values, respectively. BMP-2, but not BMP-12 or BMP-13, promoted chondrocyte hypertrophy. These observations were interpreted as suggesting that the three BMPs increase the growth rates and modulate the compositions of engineered cartilage. It was also concluded that in vitro engineered cartilage is a suitable system for studying effects of BMPs on chondrogenesis in a well-defined environment.

GPCR-Bench: A Benchmarking Set and Practitioners' Guide for G Protein-Coupled Receptor Docking.

Science.gov (United States)

Weiss, Dahlia R; Bortolato, Andrea; Tehan, Benjamin; Mason, Jonathan S

2016-04-25

Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a publically available docking benchmarking set in the spirit of the DUD and DUD-E reference data sets for validation studies, containing 25 nonredundant high-resolution GPCR costructures with an accompanying set of diverse ligands and computational decoy molecules for each target. Benchmarking sets are often used to compare docking protocols; however, it is important to evaluate docking methods not by "retrospective" hit rates but by the actual likelihood that they will produce novel prospective hits. Therefore, docking protocols must not only rank active molecules highly but also produce good poses that a chemist will select for purchase and screening. Currently, no simple objective machine-scriptable function exists that can do this; instead, docking hit lists must be subjectively examined in a consistent way to compare between docking methods. We present here a case study highlighting considerations we feel are of importance when evaluating a method, intended to be useful as a practitioners' guide.

Rare platelet GPCR variants: what can we learn?

Science.gov (United States)

Nisar, S P; Jones, M L; Cunningham, M R; Mumford, A D; Mundell, S J

2015-07-01

Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders. © 2014 The British Pharmacological Society.

G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins from endosomes.

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Tsvetanova, Nikoleta G; Irannejad, Roshanak; von Zastrow, Mark

2015-03-13

Some G protein-coupled receptors (GPCRs), in addition to activating heterotrimeric G proteins in the plasma membrane, appear to elicit a "second wave" of G protein activation after ligand-induced internalization. We briefly summarize evidence supporting this view and then discuss what is presently known about the functional significance of GPCR-G protein activation in endosomes. Endosomal activation can shape the cellular response temporally by prolonging its overall duration, and may shape the response spatially by moving the location of intracellular second messenger production relative to effectors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Role of spatial inhomogenity in GPCR dimerisation predicted by receptor association-diffusion models

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Deshpande, Sneha A.; Pawar, Aiswarya B.; Dighe, Anish; Athale, Chaitanya A.; Sengupta, Durba

2017-06-01

G protein-coupled receptor (GPCR) association is an emerging paradigm with far reaching implications in the regulation of signalling pathways and therapeutic interventions. Recent super resolution microscopy studies have revealed that receptor dimer steady state exhibits sub-second dynamics. In particular the GPCRs, muscarinic acetylcholine receptor M1 (M1MR) and formyl peptide receptor (FPR), have been demonstrated to exhibit a fast association/dissociation kinetics, independent of ligand binding. In this work, we have developed a spatial kinetic Monte Carlo model to investigate receptor homo-dimerisation at a single receptor resolution. Experimentally measured association/dissociation kinetic parameters and diffusion coefficients were used as inputs to the model. To test the effect of membrane spatial heterogeneity on the simulated steady state, simulations were compared to experimental statistics of dimerisation. In the simplest case the receptors are assumed to be diffusing in a spatially homogeneous environment, while spatial heterogeneity is modelled to result from crowding, membrane micro-domains and cytoskeletal compartmentalisation or ‘corrals’. We show that a simple association-diffusion model is sufficient to reproduce M1MR association statistics, but fails to reproduce FPR statistics despite comparable kinetic constants. A parameter sensitivity analysis is required to reproduce the association statistics of FPR. The model reveals the complex interplay between cytoskeletal components and their influence on receptor association kinetics within the features of the membrane landscape. These results constitute an important step towards understanding the factors modulating GPCR organisation.

Promoter switching allows simultaneous transcription of LANA and K14/vGPCR of Kaposi's sarcoma-associated herpesvirus

International Nuclear Information System (INIS)

Staudt, Michelle R.; Dittmer, Dirk P.

2006-01-01

Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity arises during lytic reactivation, however, as the bicistronic K14/vGPCR transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second, downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed during de novo infection or lytic reactivation. Transactivation of LANAp-i and K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional profiling following viral reactivation support promoter reporter phenotypes. In sum, cis-elements within the LANAp were selected to ensure faithful expression of LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle despite potential interference from K14/vGPCRp activity

Balancing focused combinatorial libraries based on multiple GPCR ligands

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Soltanshahi, Farhad; Mansley, Tamsin E.; Choi, Sun; Clark, Robert D.

2006-08-01

G-Protein coupled receptors (GPCRs) are important targets for drug discovery, and combinatorial chemistry is an important tool for pharmaceutical development. The absence of detailed structural information, however, limits the kinds of combinatorial design techniques that can be applied to GPCR targets. This is particularly problematic given the current emphasis on focused combinatorial libraries. By linking an incremental construction method (OptDesign) to the very fast shape-matching capability of ChemSpace, we have created an efficient method for designing targeted sublibraries that are topomerically similar to known actives. Multi-objective scoring allows consideration of multiple queries (actives) simultaneously. This can lead to a distribution of products skewed towards one particular query structure, however, particularly when the ligands of interest are quite dissimilar to one another. A novel pivoting technique is described which makes it possible to generate promising designs even under those circumstances. The approach is illustrated by application to some serotonergic agonists and chemokine antagonists.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

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Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

A new inhibitor of the ?-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

OpenAIRE

Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, St?phane A.

2017-01-01

In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, ?-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of ?-arrestin recruitment to the receptor and ?-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecul...

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

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Groot-Kormelink Paul J

2012-10-01

Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/Gαs/AC/cAMP/PKA signaling cascade.

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Li, Ting; Liu, Nannan

2017-12-01

This study explores the role of G-protein-coupled receptor-intracellular signaling in the development of P450-mediated insecticide resistance in mosquitoes, Culex quinquefasciatus , focusing on the essential function of the GPCRs and their downstream effectors of Gs alpha subunit protein (Gαs) and adenylyl cyclase (ACs) in P450-mediated insecticide resistance of Culex mosquitoes. Our RNAi-mediated functional study showed that knockdown of Gαs caused the decreased expression of the downstream effectors of ACs and PKAs in the GPCR signaling pathway and resistance P450 genes, whereas knockdown of ACs decreased the expression of PKAs and resistance P450 genes. Knockdown of either Gαs or ACs resulted in an increased susceptibility of mosquitoes to permethrin. These results add significantly to our understanding of the molecular basis of resistance P450 gene regulation through GPCR/Gαs/AC/cAMP-PKA signaling pathways in the insecticide resistance of mosquitoes. The temporal and spatial dynamic analyses of GPCRs, Gαs, ACs, PKAs, and P450s in two insecticide resistant mosquito strains revealed that all the GPCR signaling pathway components tested, namely GPCRs, Gαs, ACs and PKAs, were most highly expressed in the brain for both resistant strains, suggesting the role played by these genes in signaling transduction and regulation. The resistance P450 genes were mainly expressed in the brain, midgut and malpighian tubules (MTs), suggesting their critical function in the central nervous system and importance for detoxification. The temporal dynamics analysis for the gene expression showed a diverse expression profile during mosquito development, indicating their initially functional importance in response to exposure to insecticides during their life stages.

Engineering of blood vessel patterns by angio-morphogens [angiotropins]: non-mitogenic copper-ribonucleoprotein cytokins [CuRNP ribokines] with their metalloregulated constituents of RAGE-binding S100-EF-hand proteins and extracellular RNA bioaptamers in vascular remodeling of tissue and angiogenesis in vitro

Energy Technology Data Exchange (ETDEWEB)

Wissler, J.H. [ARCONS Applied Research, Bad Nauheim (Germany)

2001-12-01

Tissue vascularization is requisite to successful cell-based therapies, biomaterial design and implant integration. Thus, known problems in ossointegration of avascular implants in connection with the generation of bone tissue reflect arrays of general problems of socio-economic relevance existing in reparative medicine still waiting for to be solved. For this purpose, morphogenesis and remodeling of endothelial angio-architectures in tissue and in vitro by isolated non-mitogenic angio-morphogens [angiotropins] are considered in terms of their structure, function and action mechanisms. Extracellular angiotropins are secreted by activated leukocytes/monocytes/macrophages. They are a family of cytokines with morphogen bioactivity selectively directed to endothelial cells. Their structure was deciphered as metalloregulated copper-ribonucleoproteins [CuRNP ribokines]. They are built up of angiotropin-related S100-EF-hand protein [ARP] and highly modified and edited 5'end-phosphorylated RNA [ARNA], complexed together by copper ions. Oxidant-sensitive ARNA and their precursors represent novel types in a RNA world: They are the first isolated and sequenced forms of extracellular RNA [eRNA], may act as cytokine and bioaptamer, contain isoguanosine [crotonoside] as modified nucleoside and show up copper as RNA-structuring transition metal ion. By metalloregulated bioaptamer functions, ARNA impart novel biofunctions to RAGE-binding S100-EF-hand proteins. Angiotropin morphogens were shown suitable for neointiation and remodeling of blood vessel patterns in different, adult, embryonal and artificial tissues. These neovascular patterns manifest regulated hemodynamics for preventing tissue necrosis, supporting tissue functions and promoting wound healing. As evaluated in skin and muscle vascularization, the neovascular patterns are integrated into homeostatic control mechanisms of tissue. Thus, the morphogens show up beneficial perspectives and are suggested useful tools

A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium

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Ramsay, Joshua P.; Williamson, Neil R.; Spring, David R.; Salmond, George P. C.

2011-01-01

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air–liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen. PMID:21873216

A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium.

Science.gov (United States)

Ramsay, Joshua P; Williamson, Neil R; Spring, David R; Salmond, George P C

2011-09-06

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air-liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen.

Self-Checking Cell-Based Assays for GPCR Desensitization and Resensitization.

Science.gov (United States)

Fisher, Gregory W; Fuhrman, Margaret H; Adler, Sally A; Szent-Gyorgyi, Christopher; Waggoner, Alan S; Jarvik, Jonathan W

2014-09-01

G protein-coupled receptors (GPCRs) play stimulatory or modulatory roles in numerous physiological states and processes, including growth and development, vision, taste and olfaction, behavior and learning, emotion and mood, inflammation, and autonomic functions such as blood pressure, heart rate, and digestion. GPCRs constitute the largest protein superfamily in the human and are the largest target class for prescription drugs, yet most are poorly characterized, and of the more than 350 nonolfactory human GPCRs, over 100 are orphans for which no endogenous ligand has yet been convincingly identified. We here describe new live-cell assays that use recombinant GPCRs to quantify two general features of GPCR cell biology-receptor desensitization and resensitization. The assays employ a fluorogen-activating protein (FAP) reporter that reversibly complexes with either of two soluble organic molecules (fluorogens) whose fluorescence is strongly enhanced when complexed with the FAP. Both assays require no wash or cleanup steps and are readily performed in microwell plates, making them adaptable to high-throughput drug discovery applications. © 2014 Society for Laboratory Automation and Screening.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

Science.gov (United States)

Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

2012-02-23

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation

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Aaron W. James

2013-01-01

Full Text Available Mesenchymal stem cells (MSC are multipotent cells, functioning as precursors to a variety of cell types including adipocytes, osteoblasts, and chondrocytes. Between osteogenic and adipogenic lineage commitment and differentiation, a theoretical inverse relationship exists, such that differentiation towards an osteoblast phenotype occurs at the expense of an adipocytic phenotype. This balance is regulated by numerous, intersecting signaling pathways that converge on the regulation of two main transcription factors: peroxisome proliferator-activated receptor-γ (PPARγ and Runt-related transcription factor 2 (Runx2. These two transcription factors, PPARγ and Runx2, are generally regarded as the master regulators of adipogenesis and osteogenesis. This review will summarize signaling pathways that govern MSC fate towards osteogenic or adipocytic differentiation. A number of signaling pathways follow the inverse balance between osteogenic and adipogenic differentiation and are generally proosteogenic/antiadipogenic stimuli. These include β-catenin dependent Wnt signaling, Hedgehog signaling, and NELL-1 signaling. However, other signaling pathways exhibit more context-dependent effects on adipogenic and osteogenic differentiation. These include bone morphogenic protein (BMP signaling and insulin growth factor (IGF signaling, which display both proosteogenic and proadipogenic effects. In summary, understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.

Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements.

Science.gov (United States)

Stolwijk, Judith A; Matrougui, Khalid; Renken, Christian W; Trebak, Mohamed

2015-10-01

The past 20 years has seen significant growth in using impedance-based assays to understand the molecular underpinning of endothelial and epithelial barrier function in response to physiological agonists and pharmacological and toxicological compounds. Most studies on barrier function use G protein-coupled receptor (GPCR) agonists which couple to fast and transient changes in barrier properties. The power of impedance-based techniques such as electric cell-substrate impedance sensing (ECIS) resides in its ability to detect minute changes in cell layer integrity label-free and in real-time ranging from seconds to days. We provide a comprehensive overview of the biophysical principles, applications, and recent developments in impedance-based methodologies. Despite extensive application of impedance analysis in endothelial barrier research, little attention has been paid to data analysis and critical experimental variables, which are both essential for signal stability and reproducibility. We describe the rationale behind common ECIS data presentation and interpretation and illustrate practical guidelines to improve signal intensity by adapting technical parameters such as electrode layout, monitoring frequency, or parameter (resistance versus impedance magnitude). Moreover, we discuss the impact of experimental parameters, including cell source, liquid handling, and agonist preparation on signal intensity and kinetics. Our discussions are supported by experimental data obtained from human microvascular endothelial cells challenged with three GPCR agonists, thrombin, histamine, and sphingosine-1-phosphate.

Morphogenic Protein RodZ Interacts with Sporulation Specific SpoIIE in Bacillus subtilis.

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Muchová, Katarína; Chromiková, Zuzana; Bradshaw, Niels; Wilkinson, Anthony J; Barák, Imrich

2016-01-01

The first landmark in sporulation of Bacillus subtilis is the formation of an asymmetric septum followed by selective activation of the transcription factor σF in the resulting smaller cell. How the morphological transformations that occur during sporulation are coupled to cell-specific activation of transcription is largely unknown. The membrane protein SpoIIE is a constituent of the asymmetric sporulation septum and is a crucial determinant of σF activation. Here we report that the morphogenic protein, RodZ, which is essential for cell shape determination, is additionally required for asymmetric septum formation and sporulation. In cells depleted of RodZ, formation of asymmetric septa is disturbed and σF activation is perturbed. During sporulation, we found that SpoIIE recruits RodZ to the asymmetric septum. Moreover, we detected a direct interaction between SpoIIE and RodZ in vitro and in vivo, indicating that SpoIIE-RodZ may form a complex to coordinate asymmetric septum formation and σF activation. We propose that RodZ could provide a link between the cell shape machinery and the coordinated morphological and developmental transitions required to form a resistant spore.

Mild salinity stimulates a stress-induced morphogenic response in Arabidopsis thaliana roots.

Science.gov (United States)

Zolla, Gaston; Heimer, Yair M; Barak, Simon

2010-01-01

Plant roots exhibit remarkable developmental plasticity in response to local soil conditions. It is shown here that mild salt stress stimulates a stress-induced morphogenic response (SIMR) in Arabidopsis thaliana roots characteristic of several other abiotic stresses: the proliferation of lateral roots (LRs) with a concomitant reduction in LR and primary root length. The LR proliferation component of the salt SIMR is dramatically enhanced by the transfer of seedlings from a low to a high NO3- medium, thereby compensating for the decreased LR length and maintaining overall LR surface area. Increased LR proliferation is specific to salt stress (osmotic stress alone has no stimulatory effect) and is due to the progression of more LR primordia from the pre-emergence to the emergence stage, in salt-stressed plants. In salt-stressed seedlings, greater numbers of LR primordia exhibit expression of a reporter gene driven by the auxin-sensitive DR5 promoter than in unstressed seedlings. Moreover, in the auxin transporter mutant aux1-7, the LR proliferation component of the salt SIMR is completely abrogated. The results suggest that salt stress promotes auxin accumulation in developing primordia thereby preventing their developmental arrest at the pre-emergence stage. Examination of ABA and ethylene mutants revealed that ABA synthesis and a factor involved in the ethylene signalling network also regulate the LR proliferation component of the salt SIMR.

Combining on-chip synthesis of a focused combinatorial library with computational target prediction reveals imidazopyridine GPCR ligands.

Science.gov (United States)

Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

2014-01-07

Using the example of the Ugi three-component reaction we report a fast and efficient microfluidic-assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand-target associations. We identified an innovative GPCR-modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and adrenergic α1A/B receptor antagonists. Our results suggest the tight integration of microfluidics-assisted synthesis with computer-based target prediction as a viable approach to rapidly generate bioactivity-focused combinatorial compound libraries with high success rates. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse.

Directory of Open Access Journals (Sweden)

Helen Waller-Evans

2010-11-01

Full Text Available Adhesion-GPCRs provide essential cell-cell and cell-matrix interactions in development, and have been implicated in inherited human diseases like Usher Syndrome and bilateral frontoparietal polymicrogyria. They are the second largest subfamily of seven-transmembrane spanning proteins in vertebrates, but the function of most of these receptors is still not understood. The orphan Adhesion-GPCR GPR126 has recently been shown to play an essential role in the myelination of peripheral nerves in zebrafish. In parallel, whole-genome association studies have implicated variation at the GPR126 locus as a determinant of body height in the human population. The physiological function of GPR126 in mammals is still unknown. We describe a targeted mutation of GPR126 in the mouse, and show that GPR126 is required for embryonic viability and cardiovascular development.

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

Science.gov (United States)

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S; Jain, Shalini; Lowell, Bradford B; Krashes, Michael J; Wess, Jürgen

2016-01-08

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling.

Science.gov (United States)

Bachmann, Verena A; Mayrhofer, Johanna E; Ilouz, Ronit; Tschaikner, Philipp; Raffeiner, Philipp; Röck, Ruth; Courcelles, Mathieu; Apelt, Federico; Lu, Tsan-Wen; Baillie, George S; Thibault, Pierre; Aanstad, Pia; Stelzl, Ulrich; Taylor, Susan S; Stefan, Eduard

2016-07-12

Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein-protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl-terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions.

Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

Science.gov (United States)

Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert;

Complications Associated With the Use of Recombinant Human Bone Morphogenic Protein-2 in Ridge Augmentation: A Case Report.

Science.gov (United States)

Dragonas, Panagiotis; Palin, Charles; Khan, Saba; Gajendrareddy, Praveen K; Weiner, Whitney D

2017-10-01

This case report aims to describe in detail a complication associated with resorption of regenerated bone following implant placement and ridge augmentation using recombinant human bone morphogenic protein-2 (rhBMP-2) in combination with allograft and xenograft. Bilateral maxillary sinus and ridge augmentation procedures were completed using rhBMP-2 combined with allograft and xenograft. Five months later, significant bone augmentation was achieved, which allowed for the placement of 4 implants. Upon stage 2 surgery, significant dehiscence was noted in all implants. Treatment steps to address this complication included implant removal, guided bone regeneration with xenograft only, and placement of new implants followed by soft-tissue grafting. At the time of publication, this patient is status 1½ years post case completion with maintenance of therapy outcomes. Off-label use of rhBMP-2 has gained significant acceptance in implant dentistry. However, there is limited evidence regarding the bone maturation process when rhBMP-2 is combined with other biomaterials. More research may be needed regarding the timing and process of bone healing in the presence of rhBMP-2, in an effort to avoid surgical complications.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

The GPCR membrane receptor, DopEcR, mediates the actions of both dopamine and ecdysone to control sex pheromone perception in an insect

Directory of Open Access Journals (Sweden)

Antoine eAbrieux

2014-09-01

Full Text Available Olfactory information mediating sexual behavior is crucial for reproduction in many animals, including insects. In male moths, the macroglomerular complex of the primary olfactory center, the antennal lobe (AL is specialized in the treatment of information on the female-emitted sex pheromone. Evidence is accumulating that modulation of behavioral pheromone responses occurs through neuronal plasticity via the action of hormones and/or catecholamines. We recently showed that a G-protein-coupled receptor (GPCR, AipsDopEcR, with its homologue known in Drosophila for its double affinity to the main insect steroid hormone 20-hydroxyecdysone (20E, and dopamine (DA, present in the ALs, is involved in the behavioral response to pheromone in the moth, Agrotis ipsilon. Here we tested the role of AipsDopEcR as compared to nuclear 20E receptors in central pheromone processing combining receptor inhibition with intracellular recordings of AL neurons. We show that the sensitivity of AL neurons for the pheromone in males decreases strongly after AipsDopEcR-dsRNA injection but also after inhibition of nuclear 20E receptors. Moreover we tested the involvement of 20E and DA in the receptor-mediated behavioral modulation in wind tunnel experiments, using ligand applications and receptor inhibition treatments. We show that both ligands are necessary and act on AipsDopEcR-mediated behavior. Altogether these results indicate that the GPCR membrane receptor, AipsDopEcR, controls sex pheromone perception through the action of both 20E and DA in the central nervous system, probably in concert with 20E action through nuclear receptors.

GPCRM: a homology modeling web service with triple membrane-fitted quality assessment of GPCR models.

Science.gov (United States)

Miszta, Przemyslaw; Pasznik, Pawel; Jakowiecki, Jakub; Sztyler, Agnieszka; Latek, Dorota; Filipek, Slawomir

2018-05-21

Due to the involvement of G protein-coupled receptors (GPCRs) in most of the physiological and pathological processes in humans they have been attracting a lot of attention from pharmaceutical industry as well as from scientific community. Therefore, the need for new, high quality structures of GPCRs is enormous. The updated homology modeling service GPCRM (http://gpcrm.biomodellab.eu/) meets those expectations by greatly reducing the execution time of submissions (from days to hours/minutes) with nearly the same average quality of obtained models. Additionally, due to three different scoring functions (Rosetta, Rosetta-MP, BCL::Score) it is possible to select accurate models for the required purposes: the structure of the binding site, the transmembrane domain or the overall shape of the receptor. Currently, no other web service for GPCR modeling provides this possibility. GPCRM is continually upgraded in a semi-automatic way and the number of template structures has increased from 20 in 2013 to over 90 including structures the same receptor with different ligands which can influence the structure not only in the on/off manner. Two types of protein viewers can be used for visual inspection of obtained models. The extended sortable tables with available templates provide links to external databases and display ligand-receptor interactions in visual form.

Bone Morphogenic Protein-2 (rhBMP2)-Loaded Silk Fibroin Scaffolds to Enhance the Osteoinductivity in Bone Tissue Engineering

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Du, Guang-Yu; He, Sheng-Wei; Sun, Chuan-Xiu; Mi, Li-Dong

2017-10-01

There is an increasing demand for formulations of silk fibroin (SF) scaffolds in biomedical applications. SF was crosslinked via glutaraldehyde with osteoinductive recombinant human bone morphogenic protein-2 (rhBMP2) of different ratios viz. (i) 3% SF with no rhBMP2 (SF), (ii) 3% SF with equal amount of rhBMP2 (SF+BMP2), and (iii) 12% SF with 3% of rhBMP2 (4SF+BMP2), and these solutions were used in electrospinning-based fabrication of nanoscaffolds for evaluating increased osteoinductive potential of SF scaffolds with rhBMP2. Stress-strain relationship suggested there is no loss in mechanical strength of fibers with addition of rhBMP2, and mechanical strength of scaffold was improved with increase in concentration of SF. rhBMP2 association increased the water retention capacity of scaffold as evident from swelling studies. Viability of hMSCs was found to be higher in conjugated scaffolds, and scaffolds do not exhibit any cytotoxicity towards guest cells. Cells were found to have higher alkaline phosphatase activity in conjugated scaffolds under in vitro and in vivo conditions which establishes the increased osteoinductivity of the novel construct. The scaffolds were found to be effective for in vivo bone formation as well.

GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome.

Science.gov (United States)

Zhang, Jian; Yang, Jianyi; Jang, Richard; Zhang, Yang

2015-08-04

Experimental structure determination remains difficult for G protein-coupled receptors (GPCRs). We propose a new hybrid protocol to construct GPCR structure models that integrates experimental mutagenesis data with ab initio transmembrane (TM) helix assembly simulations. The method was tested on 24 known GPCRs where the ab initio TM-helix assembly procedure constructed the correct fold for 20 cases. When combined with weak homology and sparse mutagenesis restraints, the method generated correct folds for all the tested cases with an average Cα root-mean-square deviation 2.4 Å in the TM regions. The new hybrid protocol was applied to model all 1,026 GPCRs in the human genome, where 923 have a high confidence score and are expected to have correct folds; these contain many pharmaceutically important families with no previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin, and Neuropeptide Y receptors. The results demonstrate new progress on genome-wide structure modeling of TM proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

A G protein-coupled receptor (GPCR) in red: live cell imaging of the kappa opioid receptor-tdTomato fusion protein (KOPR-tdT) in neuronal cells

Science.gov (United States)

Huang, Peng; Chiu, Yi-Ting; Chen, Chongguang; Wang, Yujun; Liu-Chen, Lee-Yuan

2013-01-01

Introduction In contrast to green fluorescent protein and variants (GFPs), red fluorescent proteins (RFPs) have rarely been employed for generation of GPCR fusion proteins, likely because of formation of aggregates and cell toxicity of some RFPs. Among all the RFPs available, tdTomato (tdT), one of the non-aggregating RFP, has the highest brightness score (about 3 times that of eGFP) and unsurpassed photostability. Methods We fused tdT to the KOPR C-terminus. The KOPR-tdT cDNA construct was transfected into Neuro2A mouse neuroblastoma cell line (Neuro2A cells) and rat cortical primary neurons for characterization of pharmacological properties and imaging studies on KOPR trafficking. Results KOPR-tdT retained KOPR properties (cell surface expression, ligand binding, agonist-induced signaling and internalization) when expressed in Neuro2A cells and rat primary cortical neurons. Live cell imaging of KOPR-tdT enables visualization of time course of agonist-induced internalization of KOPR in real time for 60 min, without photobleaching and apparent cell toxicity. U50,488H-induced KOPR internalization occurred as early as 4 min and plateaued at about 30 min. A unique pattern of internalized KOPR in processes of primary neurons was induced by U50,488H. Discussion tdT is an alternative to, or even a better tool than, GFPs for fusing to GPCR for trafficking studies, because tdT has higher brightness and thus better resolution and less photobleaching problems due to reduced laser power used. It also has advantages associated with its longer-wavelength emission including spectral separation from autofluorescence and GFPs, reduced cell toxicity the laser may impose, and greater tissue penetration. These advantages of tdT over GPFs may be critical for live cell imaging studies of GPCRs in vitro and for studying GPCRs in vivo because of their low abundance. PMID:23856011

A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

Science.gov (United States)

Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

2017-04-01

In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

'Good Governance' dan 'Governability'

Directory of Open Access Journals (Sweden)

- Pratikno

2005-03-01

Full Text Available The article endeavors to trace the outset of governance concept, its dominant meanings and discourse, and its implication towards governability. The central role of government in the governing processes has predominantly been adopted. The concept of governance was emerged precisely in the context of the failure of government as key player in regulation, economic redistribution and political participation. Governance is therefore aimed to emphasize pattern of governing which are based both on democratic mechanism and sound development management. However, practices of such good governance concept –which are mainly adopted and promoted by donor states and agencies– tend to degrade state and/or government authority and legitimacy. Traditional function of the state as sole facilitator of equal societal, political and legal membership among citizens has been diminished. The logic of fair competition has been substituted almost completely by the logic of free competition in nearly all sectors of public life. The concept and practices of good governance have resulted in decayed state authority and failed state which in turn created a condition for "ungovernability". By promoting democratic and humane governance, the article accordingly encourages discourse to reinstall and bring the idea of accountable state back in.

Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@med.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan); Sekiguchi, Toshio [Noto Marine Laboratory, Division of Marine Environmental Studies, Institute of Nature and Environmental Technology, Kanazawa University, Ishikawa, 927-0553 (Japan); Nagata, Sayaka [Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692 (Japan); Jiang, Danfeng; Hayashi, Hidetaka [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan); Murakami, Manabu [Department of Pharmacology, Hirosaki University, Graduate School of Medicine, Hirosaki, 036-8562 (Japan); Hattori, Yuichi [Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194 (Japan); Kitamura, Kazuo [Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan)

2016-02-19

Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM{sub 1} receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM{sub 1} receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM{sub 1} receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific [{sup 125}I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β{sub 2}-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM{sub 1} receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.

Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

International Nuclear Information System (INIS)

Kuwasako, Kenji; Sekiguchi, Toshio; Nagata, Sayaka; Jiang, Danfeng; Hayashi, Hidetaka; Murakami, Manabu; Hattori, Yuichi; Kitamura, Kazuo; Kato, Johji

2016-01-01

Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM_1 receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM_1 receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM_1 receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific ["1"2"5I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β_2-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM_1 receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.

Morphogenes bolA and mreB mediate the photoregulation of cellular morphology during complementary chromatic acclimation in Fremyella diplosiphon.

Science.gov (United States)

Singh, Shailendra P; Montgomery, Beronda L

2014-07-01

Photoregulation of pigmentation during complementary chromatic acclimation (CCA) is well studied in Fremyella diplosiphon; however, mechanistic insights into the CCA-associated morphological changes are still emerging. F. diplosiphon cells are rectangular under green light (GL), whereas cells are smaller and spherical under red light (RL). Here, we investigate the role of morphogenes bolA and mreB during CCA using gene expression and gene function analyses. The F. diplosiphon bolA gene is essential as its complete removal from the genome was unsuccessful. Depletion of bolA resulted in slow growth, morphological defects and the accumulation of high levels of reactive oxygen species in a partially segregated ΔbolA strain. Higher expression of bolA was observed under RL and was correlated with lower expression of mreB and mreC genes in wild type. In a ΔrcaE strain that lacks the red-/green-responsive RcaE photoreceptor, the expression of bolA and mre genes was altered under both RL and GL. Observed gene expression relationships suggest that mreB and mreC expression is controlled by RcaE-dependent photoregulation of bolA expression. Expression of F. diplosiphon bolA and mreB homologues in Escherichia coli demonstrated functional conservation of the encoded proteins. Together, these studies establish roles for bolA and mreB in RcaE-dependent regulation of cellular morphology. © 2014 John Wiley & Sons Ltd.

The societal metamorphosis of energy

Energy Technology Data Exchange (ETDEWEB)

Forscher, F.

1986-01-01

This paper proposes that in its largest dimension, energy management will help to bring about needed morphogenic readjustment. The individual, the private sector, and the government, in all their decisions everywhere, must include the concept of energy. Energy management must, in effect, become a subconscious habit of each of us, like the time of day is a subconscious state of mind.

Regulation of Epithelial Morphogenesis by the G-Protein Coupled Receptor Mist and its Ligand Fog*

Science.gov (United States)

Manning, Alyssa J.; Peters, Kimberly A.; Peifer, Mark; Rogers, Stephen L.

2014-01-01

Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells, and used RNAi-based screening to identify Mist, a Drosophila G protein-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID:24222713

Bone Morphogenic Protein 4-Smad-Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function.

Science.gov (United States)

Hu, Weining; Zhang, Yang; Wang, Li; Lau, Chi Wai; Xu, Jian; Luo, Jiang-Yun; Gou, Lingshan; Yao, Xiaoqiang; Chen, Zhen-Yu; Ma, Ronald Ching Wan; Tian, Xiao Yu; Huang, Yu

2016-03-01

Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus. We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα. The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice. © 2016 American Heart Association, Inc.

Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case.

Science.gov (United States)

Di Pizio, Antonella; Kruetzfeldt, Louisa-Marie; Cheled-Shoval, Shira; Meyerhof, Wolfgang; Behrens, Maik; Niv, Masha Y

2017-08-15

Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

Evaluating e-Government and Good Governance Correlation

Directory of Open Access Journals (Sweden)

Suhardi Suhardi

2016-03-01

Full Text Available Assessing the achievement of Indonesian government institutions in implementing e-government has been conducted since around a decade ago. Several national assessments are available with almost the same ranking results. There is an agreement that the ultimate goal of e-government implementation is to achieve good government governance (GGG, while success stories of e-government require good governance practices. This study explored the correlation between e-government achievement and GGG achievement in Indonesia. Spearman’s rank correlation was used to characterize the relationship strength between e-government assessment results and good governance assessment results. The data were collected from institutions that participated in e-government and good governance assessments. The results showed that the correlation between these two entities is not very strong. Most cases showed that e-government implementation and the achievement of good governance have only a moderate positive correlation and none of the studied cases indicated a significant connection. This result can be attributed to the lack of emphasis on goals achievement in the assessments. Thus, it is recommended that future Indonesian e-government assessments should involve impact indicators.

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

Science.gov (United States)

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

E-Government Partnerships Across Levels of Government

OpenAIRE

Charbit, Claire; Michalun, Varinia

2009-01-01

E-government Partnerships across Levels of Government, is an overview of the challenges and approaches to creating a collaborative and cooperative partnership across levels of government for e-government development and implementation.

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

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Verd, Berta; Crombach, Anton

2017-01-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory

What governs governance, and how does it evolve? The sociology of governance-in-action.

Science.gov (United States)

Fox, Nick J; Ward, Katie J

2008-09-01

Governance addresses a wide range of issues including social, economic and political continuity, security and integrity, individual and collective safety and the liberty and rights to self-actualization of citizens. Questions to be answered include how governance can be achieved and sustained within a social context imbued with cultural values and in which power is distributed unevenly and dynamically, and how governance impacts on individuals and institutions. Drawing on Gramscian notions of hegemony and consent, and recent political science literatures on regulation and meta-regulation, this paper develops a sociological model of governance that emphasizes a dynamic and responsive governance in action. Empirical data from a study of pharmaceutical governance is used to show how multiple institutions and actors are involved in sustaining effective governance. The model addresses issues of how governance is sustained in the face of change, why governance of practices varies from setting to setting, and how governance is achieved without legislation.

The influence of corporate governance on project governance

OpenAIRE

Gonda, Pavel

2011-01-01

This work identifies the interaction between corporate governance and project management in project governance. It begins with introduction of basics of corporate governance and various principles of corporate governance in chosen countries and organizations. Further it introduces theoretical background of project governance and its connection and to corporate governance. In practical part work analyzes the level of compliancy with Swiss codex of best praxis in chosen company. The results con...

Engineering governance: introducing a governance meta framework.

OpenAIRE

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

2011-01-01

There is a need for a framework that depicts strategic choices within an organisation with regard to potential governance structures. The governance meta framework provides the necessary structure in the current developments of governance. Performance as well as conformance are embedded in this framework and provide the balance for all governance domains. (aut.ref.)

Changes in Serum Levels of Bone Morphogenic Protein 4 and Inflammatory Cytokines after Bariatric Surgery in Severely Obese Korean Patients with Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Mee Kyoung Kim

2013-01-01

Full Text Available Serum bone morphogenic protein- (BMP- 4 levels are associated with human adiposity. The aim of this study was to investigate changes in serum levels of BMP-4 and inflammatory cytokines after Roux-en-Y gastric bypass (RYGB. Fifty-seven patients with type 2 diabetes underwent RYGB. Serum levels of BMP-4 and various inflammatory markers, including high-sensitivity C-reactive protein (hsCRP, free fatty acids (FFAs, and plasminogen activator inhibitor- (PAI- 1, were measured before and 12 months after RYGB. Remission was defined as glycated hemoglobin <6.5% for at least 1 year in the absence of medications. Levels of PAI-1, hsCRP, and FFAs were significantly decreased at 1 year after RYGB. BMP-4 levels were also significantly lower at 1 year after RYGB than at baseline (P=0.024. Of the 57 patients, 40 (70% had diabetes remission at 1 year after surgery (remission group. Compared with patients in the nonremission group, patients in the remission group had lower PAI-1 levels and smaller visceral fat areas at baseline. There was a difference in the change in the BMP-4 level according to remission status. Our data demonstrate a significant beneficial effect of bariatric surgery on established cardiovascular risk factors and a reduction in chronic nonspecific inflammation after surgery.

48 CFR 225.7303-3 - Government-to-government agreements.

Science.gov (United States)

2010-10-01

... Military Sales 225.7303-3 Government-to-government agreements. If a government-to-government agreement... support of a specifically defined weapon system, major end item, or support item, contains language in conflict with the provisions of this section, the language of the government-to-government agreement...

Government-to-Government E-Government: A Case Study of a Federal Financial Program

Science.gov (United States)

Faokunla, Olumide Adegboyega

2012-01-01

The problem with the study of the concept of electronic government (e-Gov) is that scholars in the field have not adequately explored various dimensions of the concept. Literature on e-Gov is replete with works on the form of government to consumer e-Gov. Much less work had been done on the government to government (G2G) e-Gov. This qualitative…

Interactive governance

DEFF Research Database (Denmark)

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

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

Applying TOGAF for e-government implementation based on service oriented architecture methodology towards good government governance

Science.gov (United States)

Hodijah, A.; Sundari, S.; Nugraha, A. C.

2018-05-01

As a Local Government Agencies who perform public services, General Government Office already has utilized Reporting Information System of Local Government Implementation (E-LPPD). However, E-LPPD has upgrade limitation for the integration processes that cannot accommodate General Government Offices’ needs in order to achieve Good Government Governance (GGG), while success stories of the ultimate goal of e-government implementation requires good governance practices. Currently, citizen demand public services as private sector do, which needs service innovation by utilizing the legacy system as a service based e-government implementation, while Service Oriented Architecture (SOA) to redefine a business processes as a set of IT enabled services and Enterprise Architecture from the Open Group Architecture Framework (TOGAF) as a comprehensive approach in redefining business processes as service innovation towards GGG. This paper takes a case study on Performance Evaluation of Local Government Implementation (EKPPD) system on General Government Office. The results show that TOGAF will guide the development of integrated business processes of EKPPD system that fits good governance practices to attain GGG with SOA methodology as technical approach.

Engineering governance: introducing a governance meta framework.

NARCIS (Netherlands)

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

2011-01-01

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

Government and governance strategies in medical tourism

NARCIS (Netherlands)

Ormond, M.E.; Mainil, T.

2015-01-01

This chapter provides an overview of current government and governance strategies relative to medical tourism development and management around the world. Most studies on medical tourism have privileged national governments as key actors in medical tourism regulation and, in some cases, even

Which type of government revenue leads government expenditure?

OpenAIRE

Abdi, Zeinab; Masih, Mansur

2014-01-01

This Malaysia is a developing Islamic state that faced government budget deficit since 1998. It is undeniable that a budget deficit or inability to cover government spending is not positively seen by external parties. The optimum level of government budget is the state where government spending is totally offset by government revenue and that can be achieved through an increase in tax revenue or decrease in spending. The paper aims to discover the existence of a theoretical relationship betwe...

Interactive Governance

DEFF Research Database (Denmark)

Bang, Henrik

2016-01-01

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

Program governance

CERN Document Server

Khan, Muhammad Ehsan

2014-01-01

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

Distinct cis regulatory elements govern the expression of TAG1 in embryonic sensory ganglia and spinal cord.

Directory of Open Access Journals (Sweden)

Yoav Hadas

Full Text Available Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1 and Neurofascin (Nfasc are co-expressed in numerous neuronal cell types in the CNS and PNS - for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 5' to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system.

Alignment between business process governance and IT governance

DEFF Research Database (Denmark)

Rahimi, Fatemeh; Møller, Charles; Hvam, Lars

2014-01-01

frameworks to enable business-IT strategic alignment, efficient process and IT requirements specification, and IT-enabled business value realization. We examine the actuality of this alignment in practice through a case study conducted in a relatively mature multinational corporation. The findings indicate......The importance of business processes and the increasing centrality of IT to an organization's performance have called for a specific focus on business process governance and IT governance in contemporary enterprises. Despite the wide scope of business process management, which covers both business...... and IT domains, and the profound impact of IT on process innovations, the association between business process governance and IT governance remains under-explored. Analyzing the constituting elements of the two governance concepts, we propose the necessity of alignment between business process and IT governance...

E-Government for Good Governance in Developing Countries ...

International Development Research Centre (IDRC) Digital Library (Canada)

E-Government and E-Governance Benefits ..... Morocco's central government promotes the use of ICT in the public sector in order to enhance ...... The project's mission is to develop low-cost laptops with educational value for African children.

Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Biver, Emmanuel, E-mail: ebiver@yahoo.fr [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Soubrier, Anne-Sophie [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Thouverey, Cyril [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Cortet, Bernard [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Broux, Odile [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Caverzasio, Joseph [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Hardouin, Pierre [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)

2012-11-02

Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

Project governance: selected South African government experiments

Directory of Open Access Journals (Sweden)

G. van der Walt

2008-07-01

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

PRACTICE OF GOOD GOVERNANCE AND CORPORATE GOVERNANCE

Directory of Open Access Journals (Sweden)

Bălăceanu Cristina

2010-12-01

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

Governance or Governing – the Missing Link?

Directory of Open Access Journals (Sweden)

Luminiţa Maria Crăciun

2010-07-01

Full Text Available Governance and governing are two distinct concepts, but they intertwine. “Good governing” exercises good influence on development. “Good governance” supposes first a relationship of power focused on a series of reforms structured at three levels: the political – administrative level, the economic level, and the level of civil society. As this dimension is difficult to measure, the qualitative evaluation of the governing act raised the interest of the World Bank researchers, who elaborated and monitored the dynamics of a set of indicators, which includes six major dimensions of the governing. A retrospective concerning the image of governing in Romania during the period from 1996 to 2005 suggests a modest increase of the score: from -0.138 (1996 to 0.008 (2002; that was partially achieved based on the voice and responsibility index and on the political stability index, not on those that measure more directly the administrative performance or the integrity of the governing act. For a comparative study, we chose seven countries for the purposes of analysis (two new European Union member states: Romania and Bulgaria; two older member countries of the European Union: Slovenia and Latvia; three non-member states: Moldova, Ukraine, and Georgia, which reveal the quality of the governing from a comparative perspective. Corruption control completes the image created by the analyzed indicators. The mere formal accomplishment of commitments made in the pre-accession activity, doubled by recent internal evolutions, bring doubts about the credibility of the anticorruption reforms, as Romania continues to be considered the country with the highest CPI in the European Union. The pessimism of public opinion and the fact that only 34% of the Romanian people consider that the level of corruption will decrease in the following three years constitutes an alarm signal addressed to the governance, in view of the real reformation of the administration system

Plural Governance

DEFF Research Database (Denmark)

Mols, Niels Peter; Menard, Claude

2014-01-01

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

Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

Energy Technology Data Exchange (ETDEWEB)

Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Wang, Guan-song [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Belguise, Karine; Wang, Xiaobo [Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9 (France); Qian, Gui-sheng [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Lu, Kai-zhi [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Yi, Bin, E-mail: yibin1974@163.com [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China)

2015-08-01

Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

Governing Forest Ecosystem Services for Sustainable Environmental Governance: A Review

Directory of Open Access Journals (Sweden)

Shankar Adhikari

2018-05-01

Full Text Available Governing forest ecosystem services as a forest socio-ecological system is an evolving concept in the face of different environmental and social challenges. Therefore, different modes of ecosystem governance such as hierarchical, scientific–technical, and adaptive–collaborative governance have been developed. Although each form of governance offers important features, no one form on its own is sufficient to attain sustainable environmental governance (SEG. Thus, the blending of important features of each mode of governance could contribute to SEG, through a combination of both hierarchical and collaborative governance systems supported by scientifically and technically aided knowledge. This should be further reinforced by the broad engagement of stakeholders to ensure the improved well-being of both ecosystems and humans. Some form of governance and forest management measures, including sustainable forest management, forest certification, and payment for ecosystem services mechanisms, are also contributing to that end. While issues around commodification and putting a price on nature are still contested due to the complex relationship between different services, if these limitations are taken into account, the governance of forest ecosystem services will serve as a means of effective environmental governance and the sustainable management of forest resources. Therefore, forest ecosystem services governance has a promising future for SEG, provided limitations are tackled with due care in future governance endeavors.

Petra Governance Handbook - WP7 – Governance structures & business models : D7.3: Governance Handbook

NARCIS (Netherlands)

Veeneman, W.; Hirschhorn, F.; Klievink, A.J.; Steenhuisen, B.M.; van der Voort, H.G.

2017-01-01

This document represents the governance handbook on mobility data platforms for the PETRA project. The governance handbook provides metropolitan authorities contemplating the implementation of a mobility data platform in line with the PETRA project about governance issues and design.
The

Governance and Institutional Autonomy: Governing and Governance in Portuguese Higher Education

Science.gov (United States)

Magalhaes, Antonio; Veiga, Amelia; Ribeiro, Filipa; Amaral, Alberto

2013-01-01

This paper aims at looking at governance instruments beyond managerial technicality. It intends to do so by analysing the impact of governance reforms on the universities autonomy assumed as a regulation instrument to politically steer systems and institutions. The regulation efforts undertaken at the European and national levels reflect a trend…

Who governs energy? The challenges facing global energy governance

International Nuclear Information System (INIS)

Florini, Ann; Sovacool, Benjamin K.

2009-01-01

This article conceptualizes the energy problems facing society from a global governance perspective. It argues that a notion of 'global energy governance,' taken to mean international collective action efforts undertaken to manage and distribute energy resources and provide energy services, offers a meaningful and useful framework for assessing energy-related challenges. The article begins by exploring the concepts of governance, global governance, and global energy governance. It then examines some of the existing institutions in place to establish and carry out rules and norms governing global energy problems and describes the range of institutional design options available to policymakers. It briefly traces the role of a selection of these institutions, from inter-governmental organizations to summit processes to multilateral development banks to global action networks, in responding to energy issues, and points out their strengths and weaknesses. The article concludes by analyzing how the various approaches to global governance differ in their applicability to addressing the conundrums of global energy problems.

Who governs energy? The challenges facing global energy governance

Energy Technology Data Exchange (ETDEWEB)

Florini, Ann; Sovacool, Benjamin K. [Centre on Asia and Globalisation, Lee Kuan Yew School of Public Policy, National University of Singapore, Singapore 259772 (Singapore)

2009-12-15

This article conceptualizes the energy problems facing society from a global governance perspective. It argues that a notion of 'global energy governance,' taken to mean international collective action efforts undertaken to manage and distribute energy resources and provide energy services, offers a meaningful and useful framework for assessing energy-related challenges. The article begins by exploring the concepts of governance, global governance, and global energy governance. It then examines some of the existing institutions in place to establish and carry out rules and norms governing global energy problems and describes the range of institutional design options available to policymakers. It briefly traces the role of a selection of these institutions, from inter-governmental organizations to summit processes to multilateral development banks to global action networks, in responding to energy issues, and points out their strengths and weaknesses. The article concludes by analyzing how the various approaches to global governance differ in their applicability to addressing the conundrums of global energy problems. (author)

THE EVOLUTION OF LOCAL GOVERNMENT AND SELF-GOVERNMENT IN RUSSIA

Directory of Open Access Journals (Sweden)

Tatiana Yashchuk

2017-01-01

Full Text Available УДК 34The article highlights the main stages in the development of local government and self-gov-ernment in Russia. It shows the specifics of each stage. The formation of the Russian state was accompanied by the synthesis of the princely power and the community self-government. The genesis autocracy was accompanied by a struggle with the self-government institutions. The creation of rural and urban self-government in the second half of the XIX century was accom-panied by a debate on the social and public origin of these institutions.The Soviet state was based on the unity of the Soviet system. It concluded the discrete de-velopment of local self-government in Russia. There is no historical strong tradition of local government in this system.Objective of the article is to identify and characterize the main stages of development of local government and self-government in Russia. Show the discrete nature of the develop-ment of local self-government in Russia.The formation of the Russian state was accompanied by the synthesis of princely power and community self-government. Genesis autocracy was accompanied by a struggle with self-government institutions. The absence of territorial self-government in Russia was offset by the presence of social class municipality for a long time. Caste traditions tradition had a negative impact after the establishment of rural and urban self-government in the second half of the XIX century.During the preparation of the reforms and their implementation were discussions of the rela-tionship between the state and the community began in management. As a result, there is the inclusion of local authorities in the sphere of active state regulation. The desire of the county public to the political activity was suppressed by autocracy. The Provisional Government at-tempt to rely on the local self-government to create new authorities ended in failure.The Soviet state was based on a single management system. Certain powers

Wingless promotes proliferative growth in a gradient-independent manner.

Science.gov (United States)

Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

2009-10-06

Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

E-Government Dimension

OpenAIRE

Rosiyadi, Didi; Suryana, Nana; Cahyana, Ade; Nuryani, Nuryani

2007-01-01

Makalah ini mengemukakan E-Government Dimension yang merupakan salah satu hasil TahapanPengumpulan Data, dimana tahapan ini adalah bagian dari penelitian kompetitif di Lembaga Ilmu PengetahuanIndonesia 2007 yang sekarang sedang dilakukan. Data E-Government Dimension ini didapatkan dari berbagaisumber yang meliputi E-Government beberapa Negara di dunia, E-Government yang dibangun oleh beberapapenyedia aplikasi E-Government. E-Government Dimension terdiri dari tiga dimensi yaitu DemocraticDimen...

Leadership, Governance

Science.gov (United States)

: Environmental Documents, Reports LANL Home Calendar Search Contacts About » Leadership, Governance Leadership national security and energy challenges. Leadership, Governance Ethics, Accountability Los Alamos National . Director's Office terry wallace in leadership, governance Director Terry C. Wallace, Jr. Terry C. Wallace, Jr

Challenges in developing e-government for good governance in North Sumatra

Science.gov (United States)

Siahaan, AY

2017-01-01

E-government as one form of public administration reform in Indonesia is increasingly related to the pursuance of good governance. This paper examines the relationship between of e-government and good governance by utilizing the case study design on the implementation of e-procurement in North Sumatra. It reveals centrality of local politics and business culture in understanding resistances of both local government officials and local business which creates loopholes’ for the practice of ‘bad governance’ in all phases of e-procurement in North Sumatra province. Data transparency does not equate and guarantee the realization of good governance. Public knowledge and understanding on government decision making processes and accountability (process and policy transparency) are central to achieve good governance through e-procurement. E-procurement system does not automatically change organizational and working culture of the implementers and suppliers. This paper provides insight to the attitude and the perception of private sector engage in e-procurement towards government in implementing e-government. Resistance, digital divide and local politics interrelatedly obstruct the realization of pursuing good governance through e-procurement.

The potentiation of Mangifera casturi bark extract on interleukin- 1β and bone morphogenic protein-2 expressions during bone remodeling after tooth extraction

Directory of Open Access Journals (Sweden)

Bayu Indra Sukmana

2017-03-01

Full Text Available Background: The main oral health problem in Indonesia is the high number of tooth decay. Tooth extraction is the treatment often received by patients who experience tooth decay and the wound caused by alveolar bone resorption. Bark of Mangifera casturi has been studied and proven to contain secondary metabolite which has the ability to increase osteoblast’s activity and suppress osteoclast’s activity. Purpose: The purpose of this study was to analyze interleukin-1 beta (IL-1β and bone morphogenic protein-2 (BMP-2 activities during bone remodeling after Mangifera casturi’s bark extract treatment. Method: This study was laboratory experimental research with randomized post-test only control group design. The Mangifera casturi bark was extracted using 96% ethanol maceration and n-hexane fractionation. This study used 40 male Wistar rats which are divided into 4 groups and the tooth extraction was performed on the rats’ right mandible incisive tooth. The four groups consisted of 6.35%, 12.7%, 25.4% extract treatment group, and a control group. Wistar’s mandibles were decapitated on the 7th and 14th day after extraction. Antibody staining on preparations for the examination of IL-1β and BMP-2 expressions was done using immunohistochemistry. Result: There was a significant difference of IL-1β and BMP-2 expressions in 6,35%, 12,7%, and 25,4% treatment groups compared to control group with p<0.05. Conclusion: Mangifera casturi’s bark extract was able to suppress the IL-1β expression and increase the BMP-2 expression during bone remodeling after tooth extraction.

Renewing governance.

Science.gov (United States)

Loos, Gregory P

2003-01-01

Globalization's profound influence on social and political institutions need not be negative. Critics of globalization have often referred to the "Impossible Trinity" because decision-making must 1. respect national sovereignty, 2. develop and implement firm regulation, and 3. allow capital markets to be as free as possible. To many, such goals are mutually exclusive because history conditions us to view policy-making and governance in traditional molds. Thus, transnational governance merely appears impossible because current forms of governance were not designed to provide it. The world needs new tools for governing, and its citizens must seize the opportunity to help develop them. The rise of a global society requires a greater level of generality and inclusion than is found in most policy bodies today. Politicians need to re-examine key assumptions about government. States must develop ways to discharge their regulatory responsibilities across borders and collaborate with neighboring jurisdictions, multilateral bodies, and business. Concepts such as multilateralism and tripartism show great promise. Governments must engage civil society in the spirit of shared responsibility and democratic decision-making. Such changes will result in a renewal of the state's purpose and better use of international resources and expertise in governance.

Open government and municipalities: Beyond e-governement

Directory of Open Access Journals (Sweden)

Christian Cruz Meléndez

2017-11-01

Full Text Available This article’s purpose is to analyze egovernment and open government as tolos to strengthen the role of municipal government. It reviews the evolution of both tolos in Mexico and contains a conceptual analysis of both terms to gain an understanding of their meaning and of the reason why they are promoted for the benefit of local governments. Finally, it explores the availability of these tools in the municipalities, and how they contribute to each municipality in the fulfillment of its responsibilities.

Director remuneration, corporate governance and performance: A comparison between government linked companies vs non government linked companies

Directory of Open Access Journals (Sweden)

Nazrul Hisyam Ab Razak

2014-07-01

Full Text Available This study has examined the relationship between director’s remuneration, corporate governance structure and performance of a sample of 150 companies listed on the Bursa Malaysia from year 2008 until 2013. The sample was selected to provide matched-pair of government linked companies (GLCs and non-government linked companies (non-GLCs, as it was anticipated that these group would have different governance structure, the key difference being government ownership. The result holds even when we control for company specific characteristic such as corporate governance, company size, leverage, director’s remuneration, board size and auditors. This study uses panel based regression model to examine the impact of government control mechanism on company performance using two important measurers. These are accounting based measure proxies by ROA and non-accounting based measures by Tobin’s Q. Statistically significant relationships were found across the groupings and for different performance measures. Findings appear to suggest that there is a significant impact of government ownership on company performance after controlling for company specific characteristics.

Electronic Government

DEFF Research Database (Denmark)

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

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

WHY DOES GOVERNMENT GROW?THE SOURCESOF GOVERNMENT GROWTHFROM PUBLIC CHOICEPERSPECTIVE

Directory of Open Access Journals (Sweden)

Coskun Can Aktan, PhD

2017-01-01

Full Text Available Many empirical studies that examined the government spending concludes that the sizeand scope of government has grown considerably since the beginning of the twentiethcentury in most developed countries. If this is the fact, then we must ask and explore thefollowing questions: Why does government grow? What are the main sources ofgovernment growth? What are the main reasons of the expansion of government? Thisintroductory paper aims to answerthose and other questions regarding governmentgrowth. The paperismostlydependon public choice literature of government growth.

The Russia Corporate Governance Manual : Part I. Corporate Governance Introduced

OpenAIRE

International Finance Corporation; U.S. Department of Commerce

2004-01-01

The Russia corporate governance manual has been divided into and is published in six parts: (i) corporate governance introduced; (ii) good board practices; (iii) shareholder rights; (iv) information disclosure and transparency; (v) special focus section; and (vi) annexes model corporate governance documents. The first four parts contain chapters that focus on core corporate governance issu...

E-Government, Audit Opinion, and Performance of Local Government Administration in Indonesia

Directory of Open Access Journals (Sweden)

Bambang Sutopo

2017-12-01

Full Text Available Local governments (LGs have an important role in providing services to the community. Nevertheless, some local governments still show relatively low performance. Scores of e-government implementation and audit opinions obtained by some local governments are also relatively low. This study examines whether there are relationships between e-government, the dimensions of e-government, and audit opinion and the performance of the local government administration. There are five dimensions of the e-government i.e. policy, institutions, infrastructure, applications, and planning. The sample used in this study includes 246 local governments from 2012 to 2014. Using regression analysis, the results of this study show that e-government has a positive association with the performance of the local government administration. This is supported by the positive association of e-government’s dimensions with performance. The audit opinion is also positively associated with performance as expected. These results suggest that e-government and audit opinion can be used as indicators of the performance of local government administration.

Why Governments Intervene

DEFF Research Database (Denmark)

Knudsen, Jette Steen; Brown, Dana

2015-01-01

Why are national governments increasingly adopting policies on corporate social responsibility (CSR)? Government CSR policies have been explained either as a means of substituting or supporting (mirroring) domestic political-economic institutions and policies, or as a means for government...... to promote international competitiveness of domestic businesses. Both sets of explanations see governments as driving CSR policies to meet particular national government goals. Support is found for the thesis that CSR policies are often related to international competitiveness, yet our findings suggest...... that government goals in this regard are not necessarily pre-defined....

Transitions governance: Towards a new governance paradigm

NARCIS (Netherlands)

N. Frantzeskaki (Niki); D.A. Loorbach (Derk)

2009-01-01

textabstractThis paper presents a framework for governance in the context of large scale and long term societal change (transitions). We argue that existing theories of governance offer interesting descriptive insights for such a framework, but do not present innovative prescriptive ideas

Gobernanza Versus Gobierno Governance Versus Government

Directory of Open Access Journals (Sweden)

Dany-Robert Dufour

2009-06-01

Full Text Available El desplazamiento del término moderno de gobierno por el postmoderno de gobernanza, pone de manifiesto un nuevo lenguaje postmoderno en el que se deja entrever que ambas nociones, gobierno y gobernanza, tienden a oponerse. La gobernanza corporativa designa la toma del poder del capitalismo financiero sobre el capitalismo industrial, que no es otra cosa que, por un lado, propender por la rentabilidad máxima para los accionistas, valorizar todo en el mercado sin consideraciones morales, obligar a los actores a la búsqueda de riesgo permanente y flexibilizar las relaciones jerárquicas en la Administración de la empresa; y por el otro, la marginación de la clase obrera. La gobernanza ha llegado a los asuntos políticos convirtiéndose en modelo de gestión pública por excelencia, ella trata que el gobierno reducido a su mínima expresión guie a una sociedad civil que adquiere un papel importante en la creación y seguimiento de las diferentes políticas, es decir, que el gobierno adquiere una forma flexible de regulación, es allá donde la gobernanza política nos conduce, a la supuesta autorregulación de los intereses privados que sumados pasan a configurar el interés general. En realidad se trata de una nueva forma de dominación marcada por un desvanecimiento político, donde la sociedad civil juega en contra del Estado. La gobernanza le está tendiendo una temible trampa a la democracia, en tanto se presenta como una ampliación de la democracia materializada en una mejor participación de la sociedad civil, destruyendo la persona pública que se forma por la unión de todos los otros y convirtiéndola en representante de intereses particulares.The displacement of the modern term of government for the postmodern one of governance, reveals a new postmodern language in which one is left to guess that both notions, government and governance, tend to be opposed. Corporate governance signifies the seizure of power of financial capitalism

Governing Towards Sustainability-Conceptualizing Modes of Governance

NARCIS (Netherlands)

Lange, P. de; Driessen, P.P.J.; Sauer, A.; Bornemann, B.; Burger, P.

2013-01-01

There is a growing scientific debate regarding the suitability of certain modes of governance for promoting sustainable development (SD). However, thus far there is neither agreement on ways to meaningfully distinguish and understand governance modes nor a foundation of the aspects to be chosen

Towards a Typology of Adaptive Governance in the Digital Government Context

DEFF Research Database (Denmark)

Wang, Cancan; Medaglia, Rony; Zheng, Lei

2018-01-01

and of accountability between government and non-government actors is critical to developing different types of adaptive governance. Findings show that the distribution of decision-making power and of accountability can be decoupled, resulting in three types of adaptive governance – namely polycentric, agile......, and organic governance. We contribute to research by detailing and empirically testing the notion of adaptive governance in a digital government context, and to practice by highlighting the role of the distribution of decision-making power and of accountability in devising adaptive governance strategies....... there is an increasing need to establish forms of collaboration that can respond to swift changes in the environment related to technology and citizen demands. Drawing on the analysis of four cases of IT-related project collaboration, we put forward that the degree of sharing of decision-making power...

Transformative environmental governance

Science.gov (United States)

Chaffin, Brian C.; Garmestani, Ahjond S.; Gunderson, Lance H.; Harm Benson, Melinda; Angeler, David G.; Arnold, Craig Anthony (Tony); Cosens, Barbara; Kundis Craig, Robin; Ruhl, J.B.; Allen, Craig R.

2016-01-01

Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to alternative, more desirable, or more functional regimes by altering the structures and processes that define the system. Transformative governance is rooted in ecological theories to explain cross-scale dynamics in complex systems, as well as social theories of change, innovation, and technological transformation. Similar to adaptive governance, transformative governance involves a broad set of governance components, but requires additional capacity to foster new social-ecological regimes including increased risk tolerance, significant systemic investment, and restructured economies and power relations. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds.

Development of novel ligands for peptide GPCRs.

Science.gov (United States)

Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm

2016-12-01

Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stakeholder Governance

DEFF Research Database (Denmark)

Flak, Leif Skiftenes; Rose, Jeremy

2005-01-01

to e-Government. Originally a management theory, stakeholder theory advocates addressing the concerns of all stakeholders in a firm, as opposed to concentration on the interests of senior managers and stockholders. Apart from the original profit focus, there is no serious conceptual mismatch between...... of governance. Finally, the paper makes recommendations for future work in adapting ST to the e-government context....

WHY DOES GOVERNMENT GROW?THE SOURCESOF GOVERNMENT GROWTHFROM PUBLIC CHOICEPERSPECTIVE

OpenAIRE

Coskun Can Aktan, PhD

2017-01-01

Many empirical studies that examined the government spending concludes that the sizeand scope of government has grown considerably since the beginning of the twentiethcentury in most developed countries. If this is the fact, then we must ask and explore thefollowing questions: Why does government grow? What are the main sources ofgovernment growth? What are the main reasons of the expansion of government? Thisintroductory paper aims to answerthose and other questions regardin...

Forms of global governence

Directory of Open Access Journals (Sweden)

Maxim V. Kharkevich

2014-01-01

Full Text Available Global governance as a concept defines the meaning of contemporary world politics both as a discipline and as reality. Interdependent and globalized world requires governance, and a global government has not been formed yet. The theoretical possibility of global governance without global government is proved and justified. The purpose of this article is to analytically identify possible forms of global governance. Three such forms of global governance are identified: hierarchical, market and network. In a hierarchy the governance is due to the asymmetry of power between the parties. Market control happens via anonymous pricing mechanism. Network, in contrast to the market is characterized by a closer value link between the actors, but unlike the hierarchical relationship actors are free to leave the network. Global governance takes three forms and is being implemented by different actors. To determine the most efficient form of global governance is impossible. Efficiency depends on the match between a form and an object of government. It should be noted that meta governance is likely to remain a monopoly of institutionally strong states in global governance.

Leisure, Government and Governance: A Swedish Perspective

Science.gov (United States)

Lindstrom, Lisbeth

2011-01-01

The leisure sector has witnessed a tremendous expansion since 1960. The purpose of this article is to analyse the decisions and goals of Swedish government policy during the period 1962 to 2005. The empirical analysis covers government Propositions and governmental investigations. The fields covered are sports, culture, exercise, tourism and…

The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation

KAUST Repository

Gaffney, E. A.; Lee, S. S.

2013-01-01

© The authors 2013. Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting

China's Insurance Regulatory Reform, Corporate Governance Behavior and Insurers' Governance Effectiveness.

Science.gov (United States)

Li, Huicong; Zhang, Hongliang; Tsai, Sang-Bing; Qiu, Aichao

2017-10-17

External regulation is an important mechanism to improve corporate behavior in emerging markets. China's insurance governance regulation, which began to supervise and guide insurance corporate governance behavior in 2006, has experienced a complex process of reform. This study tested our hypotheses with a sample of 85 firms during 2010-2011, which was obtained by providing a questionnaire to all of China's shareholding insurance companies. The empirical study results generally show that China's insurance governance effectiveness has significantly improved through strict regulation. Insurance corporate governance can improve business acumen and risk-control ability, but no significant evidence was found to prove its influence on profitability, as a result of focusing less attention on governance than on management. State ownership is associated with higher corporate governance effectiveness than non-state ownership. Listed companies tend to outperform non-listed firms, and life insurance corporate governance is more effective than that of property insurers. This study not only contributes to the comprehensive understanding of corporate governance effectiveness but also to the literature by highlighting the effect of corporate governance regulation in China's insurance industry and other emerging economies of the financial sector.

Transforming Government Service

DEFF Research Database (Denmark)

Pedersen, Keld

2017-01-01

The Danish government has defined an ambitious e-government strategy aiming to increase both citizen centricity and the efficiency of government service production and delivery. This research uses dynamic capability theory to compare a highly successful and a less successful e-government program...... both aiming at realizing this strategy by reengineering back office processes and implement one-stop shopping. The research contributes to the e-government literature by identifying key differences between the two cases in terms of dynamic capabilities, by identifying the importance...

Corporate Governance

Directory of Open Access Journals (Sweden)

Dragoș-Mihail Daghie

2011-05-01

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

Improving Unsustainable Environmental Governance in South Africa: the Case for Holistic Governance

Directory of Open Access Journals (Sweden)

LJ Kotze

2006-05-01

Full Text Available Environmental law in South Africa has developed in a rapid fashion since the inception of the new constitutional dispensation in 1994. This development is evident from, inter alia, the constitutionalisation of the environmental right in section 24 of the Constitution of the Republic of South Africa, 1996. Section 24 contains amongst other provisions, directive principles that impose duties on government to protect the environment for present and future generations through reasonable legislative and other measures. It is apparent from section 24 that these measures should ensure environmental governance practices that are aimed at the achievement of sustainable results. The South African environmental governance regime is, however, characterised by fragmentation that may negate the achievement of sustainable environmental governance. It is argued in this article that, for environmental governance to become sustainable, it is necessary to integrate environmental governance efforts, possibly by way of a holistic approach to environmental governance. In light of the above, this article: investigates the nature and extent of fragmentation; explores reasons for fragmentation; discusses disadvantages of fragmented governance efforts in South Africa; investigates the concept of integration and holistic governance as means to achieve sustainable environmental governance results; and makes recommendations regarding the eventual achievement of integrated, holistic and sustainable environmental governance.

Governance in Health - The Need for Exchange and Evidence Comment on "Governance, Government, and the Search for New Provider Models".

Science.gov (United States)

Chanturidze, Tata; Obermann, Konrad

2016-05-17

Governance in health is cited as one of the key factors in balancing the concerns of the government and public sector with the interests of civil society/private players, but often remains poorly described and operationalized. Richard Saltman and Antonio Duran look at two aspects in the search for new provider models in a context of health markets signalling liberalisation: (i) the role of the government to balance public and private interests and responsibilities in delivering care through modernised governance arrangements, and (ii) the finding that operational complexities may hinder well-designed provider governance models, unless governance reflects country-specific realities. This commentary builds on the discussion by Saltman and Duran, and argues that the concept of governance needs to be clearly defined and operationalized in order to be helpful for policy debate as well as for the development of an applicable framework for performance improvement. It provides a working definition of governance and includes a reflection on the prevailing cultural norms in an organization or society upon which any governance needs to be build. It proposes to explore whether the "evidence-based governance" concept can be introduced to generate knowledge about innovative and effective governance models, and concludes that studies similar to the one by Saltman and Duran can inform this debate. © 2016 by Kerman University of Medical Sciences.

Discovering Citizens Reaction Toward E-Government: Factors in E-Government Adoption

Directory of Open Access Journals (Sweden)

Mohammad Kamel Alomari

2014-10-01

Full Text Available E-government has been considered as one approach for changing the face of government in the eyes of the citizenry. Therefore, citizens’ socialization in relation to their engagement with e-government should be explored. This study argues that citizens played a significant role in determining the success of an e-government project in the Middle Eastern country of Jordan. This paper aims to provide insight and evaluation into the factors that could influence e-government’s effective functioning in the Jordanian social community through its interaction with citizens. The study collected data from 356 Jordanian citizens via a survey, to ascertain their understanding of 10 factors that may influence their intention to use e-government services. To investigate the adoption of e-government services in depth, two departments in Jordan were selected: the Jordanian Government’s Income and Sales Tax Department (ISTD and its Driver and Vehicle Licenses Department (DVDL. The factor analysis technique was used to identify the main factors related to e-government services’ adoption. The results indicated that trust in the internet, website design, religious beliefs, internet and computer skill confidence, word of mouth, resistance to change, perceived usefulness, relative advantage and complexity are the main factors that should be considered when addressing the topic of e-government services’ adoption in Jordan. This study is different from most existing studies on e-government adoption as it empirically investigated the impact of word of mouth (WOM, wasta (favoritism, and resistance to change on e-government adoption. This study highlights the importance of considering the social cohesion of the Jordanian community when exploring factors related to e-government adoption.

Governance, Government, and the Search for New Provider Models

Directory of Open Access Journals (Sweden)

Richard B. Saltman

2016-01-01

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

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

Science.gov (United States)

Saltman, Richard B; Duran, Antonio

2015-11-03

A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory) perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome. © 2016 by Kerman University of Medical Sciences.

Government and Governance of Regional Triple Helix Interactions

Science.gov (United States)

Danson, Mike; Todeva, Emanuela

2016-01-01

This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional…

GOVERNMENT SIZE VERSUS GOVERNMENT EFFICIENCY IN A MODEL OF ECONOMIC GROWTH

Directory of Open Access Journals (Sweden)

Francisca Guedes de Oliveira

2016-04-01

Full Text Available We develop a Solow type growth model where firms produce a single homogenous good using labor, private capital and a public good. The "amount" of public good depends on current government spending and government quality. Quality is the result of the accumulation of public capital. Governments charge distortionary taxes and provide the public good, investing also in "quality" by accumulating public capital. We analyze how the composition of government spending between current expenditures and quality affects the equilibrium levels. We aim to understand the difference in terms of steady state levels between leviathan, quality driven and benevolent governments.

Transformative environmental governance

Science.gov (United States)

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

Governance matters: an ecological association between governance and child mortality.

Science.gov (United States)

Lin, Ro-Ting; Chien, Lung-Chang; Chen, Ya-Mei; Chan, Chang-Chuan

2014-09-01

Governance of a country may have widespread effects on the health of its population, yet little is known about the effect of governance on child mortality in a country that is undergoing urbanization, economic development, and disease control. We obtained indicators of six dimensions of governance (perceptions of voice and accountability, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and control of corruption) and national under-5 mortality rates for 149 countries between 1996 and 2010. We applied a semi-parametric generalized additive mixed model to examine associations after controlling for the effects of development factors (urbanization level and economy), disease control factors (hygienic conditions and vaccination rates), health expenditures, air quality, and time. Governance, development, and disease control showed clear inverse relations with the under-5 mortality rate (pcountry's need for better governance is as important as improvements in development and disease control. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Integrating adaptive governance and participatory multicriteria methods: a framework for climate adaptation governance

Directory of Open Access Journals (Sweden)

Stefania Munaretto

2014-06-01

Full Text Available Climate adaptation is a dynamic social and institutional process where the governance dimension is receiving growing attention. Adaptive governance is an approach that promises to reduce uncertainty by improving the knowledge base for decision making. As uncertainty is an inherent feature of climate adaptation, adaptive governance seems to be a promising approach for improving climate adaptation governance. However, the adaptive governance literature has so far paid little attention to decision-making tools and methods, and the literature on the governance of adaptation is in its infancy in this regard. We argue that climate adaptation governance would benefit from systematic and yet flexible decision-making tools and methods such as participatory multicriteria methods for the evaluation of adaptation options, and that these methods can be linked to key adaptive governance principles. Moving from these premises, we propose a framework that integrates key adaptive governance features into participatory multicriteria methods for the governance of climate adaptation.

Practice of good governance and corporate governance

OpenAIRE

Bălăceanu Cristina; Predonu Andreea – Monica

2010-01-01

Corporate governance reforms are occurring in countries around the globe and potentially impacting the population of the entire planet. In developing countries, such reforms occur in a larger context that is primarily defined by previous attempts at promoting “development” and recent processes of economic globalization. In this context, corporate governance reforms (in combination with the liberalising reforms associated with economic globalization), in effect re...

Role of G-protein-coupled receptor-related genes in insecticide resistance of the mosquito, Culex quinquefasciatus.

Science.gov (United States)

Li, Ting; Liu, Lena; Zhang, Lee; Liu, Nannan

2014-09-29

G-protein-coupled receptors regulate signal transduction pathways and play diverse and pivotal roles in the physiology of insects, however, the precise function of GPCRs in insecticide resistance remains unclear. Using quantitative RT-PCR and functional genomic methods, we, for the first time, explored the function of GPCRs and GPCR-related genes in insecticide resistance of mosquitoes, Culex quinquefasciatus. A comparison of the expression of 115 GPCR-related genes at a whole genome level between resistant and susceptible Culex mosquitoes identified one and three GPCR-related genes that were up-regulated in highly resistant Culex mosquito strains, HAmCq(G8) and MAmCq(G6), respectively. To characterize the function of these up-regulated GPCR-related genes in resistance, the up-regulated GPCR-related genes were knockdown in HAmCq(G8) and MAmCq(G6) using RNAi technique. Knockdown of these four GPCR-related genes not only decreased resistance of the mosquitoes to permethrin but also repressed the expression of four insecticide resistance-related P450 genes, suggesting the role of GPCR-related genes in resistance is involved in the regulation of resistance P450 gene expression. This results help in understanding of molecular regulation of resistance development in Cx. quinquefasciatus.

Energy Efficiency Governance

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-07-01

The purpose of this report is to help EE practitioners, government officials and stakeholders to establish the most effective EE governance structures, given their specific country context. It also aims to provide readers with relevant and accessible information to support the development of comprehensive and effective governance mechanisms. The International Energy Agency (IEA) conducted a global review of many elements of EE governance,including legal frameworks, institutional frameworks, funding mechanisms, co-ordination mechanisms and accountability arrangements, such as evaluation and oversight. The research tools included a survey of over 500 EE experts in 110 countries, follow-up interviews of over 120 experts in 27 countries and extensive desk study and literature searches on good EE governance.

China’s Insurance Regulatory Reform, Corporate Governance Behavior and Insurers’ Governance Effectiveness

Science.gov (United States)

Zhang, Hongliang; Qiu, Aichao

2017-01-01

External regulation is an important mechanism to improve corporate behavior in emerging markets. China’s insurance governance regulation, which began to supervise and guide insurance corporate governance behavior in 2006, has experienced a complex process of reform. This study tested our hypotheses with a sample of 85 firms during 2010–2011, which was obtained by providing a questionnaire to all of China’s shareholding insurance companies. The empirical study results generally show that China’s insurance governance effectiveness has significantly improved through strict regulation. Insurance corporate governance can improve business acumen and risk-control ability, but no significant evidence was found to prove its influence on profitability, as a result of focusing less attention on governance than on management. State ownership is associated with higher corporate governance effectiveness than non-state ownership. Listed companies tend to outperform non-listed firms, and life insurance corporate governance is more effective than that of property insurers. This study not only contributes to the comprehensive understanding of corporate governance effectiveness but also to the literature by highlighting the effect of corporate governance regulation in China’s insurance industry and other emerging economies of the financial sector. PMID:29039781

China’s Insurance Regulatory Reform, Corporate Governance Behavior and Insurers’ Governance Effectiveness

Directory of Open Access Journals (Sweden)

Huicong Li

2017-10-01

Full Text Available External regulation is an important mechanism to improve corporate behavior in emerging markets. China’s insurance governance regulation, which began to supervise and guide insurance corporate governance behavior in 2006, has experienced a complex process of reform. This study tested our hypotheses with a sample of 85 firms during 2010–2011, which was obtained by providing a questionnaire to all of China’s shareholding insurance companies. The empirical study results generally show that China’s insurance governance effectiveness has significantly improved through strict regulation. Insurance corporate governance can improve business acumen and risk-control ability, but no significant evidence was found to prove its influence on profitability, as a result of focusing less attention on governance than on management. State ownership is associated with higher corporate governance effectiveness than non-state ownership. Listed companies tend to outperform non-listed firms, and life insurance corporate governance is more effective than that of property insurers. This study not only contributes to the comprehensive understanding of corporate governance effectiveness but also to the literature by highlighting the effect of corporate governance regulation in China’s insurance industry and other emerging economies of the financial sector.

Local government financial autonomy in Nigeria: The State Joint Local Government Account

Directory of Open Access Journals (Sweden)

Jude Okafor

2010-07-01

Full Text Available This paper addresses the statutory financial relations and financial autonomy of local government in Nigeria, and the freedom of local government to generate revenue from its assigned sources without external interference. It focuses particularly on a financial instrument called the State Joint Local Government Account (SJLGA and how its operations have positively or negatively affected the financial autonomy of local government councils and the inter-relations between state and local government in Nigeria.

The politics of meta-governance in transnational private sustainability governance

OpenAIRE

Fransen, L.

2015-01-01

In order to address challenges resulting from interactions between transnational private sustainability standard organizations, initiatives emerge that meta-govern these standards. Contrary to prevailing understandings in public policy literature, such meta-governance initiatives are mostly run by nongovernmental rather than governmental actors. While literature presents the sustainability standards field as predominantly governed by one meta-governor, ISEAL, it is hardly recognized that, alo...

Theoretical Ideas of Local Government and State Government Development

Directory of Open Access Journals (Sweden)

Nikolay I. Churinov

2016-03-01

Full Text Available In this article the characteristic of a theoretical component of model of interaction of local government bodies with the central government, and also development of scientific base in the course of history is given. Relevance to this subject in the conditions of the Russian reality is added by federalism of a state system of Russia, namely a thin side in questions of competences between bodies of one hierarchy. This article, will be useful to those who deal with issues in the field of the theory of the state and the right and the municipal right. Historic facts in the form of the regulatory legal acts adopted earlier which subsequently, were a source for development of theoretical ideas of local self-government and the government are given in article.

Optimalisasi Penerapan Prinsip Good Governance Bidang Akademik dalam Upaya Mewujudkan Good University Governance

Directory of Open Access Journals (Sweden)

Hery Harjono Muljo

2014-05-01

Full Text Available This study wants to know and understand whether good governance principles have been well applied as well as the factors influencing optimization of the implementation of good governance principles on the academic field in an effort to realize good university governance in Bina Nusantara University. The study aims to evaluate the implementation of good governance principles on the academic field, know the factors that affect the implementation of good governance principles on the academic field, and improve and develop the academic areas in accordance with good governance principles in order to maximize the role of Bina Nusantara University as Good University Governance. The approach model used to understand the implementation of good governance principles was a model to educational institution using the 8 principles, namely academic freedom, shared governance, clear rights and responsibilities, selection at merit, financial stability, accountability, regular testing of standards, and the importance of close cooperation. Research used qualitative method with descriptive analysis, by analyzing the factors influencing optimization of the implementation of good governance principles, particularly on academic areas. The results achieved there were 18 factors that affect the optimization of the implementation of good governance principles. Then the factors affected the optimization ofthe implementation of good governance principles the most are operational centralization and academic decentralization which were the novelty of this study.

G protein-coupled receptor internalization assays in the high-content screening format.

Science.gov (United States)

Haasen, Dorothea; Schnapp, Andreas; Valler, Martin J; Heilker, Ralf

2006-01-01

High-content screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modeling systems. This chapter describes the measurement of G protein-coupled receptor (GPCR) internalization in the HCS format using a high-throughput, confocal cellular imaging device. GPCRs are the most successful group of therapeutic targets on the pharmaceutical market. Accordingly, the search for compounds that interfere with GPCR function in a specific and selective way is a major focus of the pharmaceutical industry today. This chapter describes methods for the ligand-induced internalization of GPCRs labeled previously with either a fluorophore-conjugated ligand or an antibody directed against an N-terminal tag of the GPCR. Both labeling techniques produce robust assay formats. Complementary to other functional GPCR drug discovery assays, internalization assays enable a pharmacological analysis of test compounds. We conclude that GPCR internalization assays represent a valuable medium/high-throughput screening format to determine the cellular activity of GPCR ligands.

Experimentalist governance

NARCIS (Netherlands)

Sabel, C.F.; Zeitlin, J.; Levi-Faur, D.

2012-01-01

A secular rise in volatility and uncertainty is overwhelming the capacities of conventional hierarchical governance and ‘command-and-control’ regulation in many settings. One significant response is the emergence of a novel, ‘experimentalist’ form of governance that establishes deliberately

Remaking Governance.

Science.gov (United States)

Carver, John

2000-01-01

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

Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia.

Directory of Open Access Journals (Sweden)

Ignat Drozdov

Full Text Available Small intestinal (SI neuroendocrine tumors (NET are increasing in incidence, however little is known about their biology. High throughput techniques such as inference of gene regulatory networks from microarray experiments can objectively define signaling machinery in this disease. Genome-wide co-expression analysis was used to infer gene relevance network in SI-NETs. The network was confirmed to be non-random, scale-free, and highly modular. Functional analysis of gene co-expression modules revealed processes including 'Nervous system development', 'Immune response', and 'Cell-cycle'. Importantly, gene network topology and differential expression analysis identified over-expression of the GPCR signaling regulators, the cAMP synthetase, ADCY2, and the protein kinase A, PRKAR1A. Seven CREB response element (CRE transcripts associated with proliferation and secretion: BEX1, BICD1, CHGB, CPE, GABRB3, SCG2 and SCG3 as well as ADCY2 and PRKAR1A were measured in an independent SI dataset (n = 10 NETs; n = 8 normal preparations. All were up-regulated (p<0.035 with the exception of SCG3 which was not differently expressed. Forskolin (a direct cAMP activator, 10(-5 M significantly stimulated transcription of pCREB and 3/7 CREB targets, isoproterenol (a selective ß-adrenergic receptor agonist and cAMP activator, 10(-5 M stimulated pCREB and 4/7 targets while BIM-53061 (a dopamine D(2 and Serotonin [5-HT(2] receptor agonist, 10(-6 M stimulated 100% of targets as well as pCREB; CRE transcription correlated with the levels of cAMP accumulation and PKA activity; BIM-53061 stimulated the highest levels of cAMP and PKA (2.8-fold and 2.5-fold vs. 1.8-2-fold for isoproterenol and forskolin. Gene network inference and graph topology analysis in SI NETs suggests that SI NETs express neural GPCRs that activate different CRE targets associated with proliferation and secretion. In vitro studies, in a model NET cell system, confirmed that transcriptional

Digital Government and Public Health

OpenAIRE

Fountain, Jane E.

2004-01-01

Digital government is typically defined as the production and delivery of information and services inside government and between government and the public using a range of information and communication technologies. Two types of government relationships with other entities are government-to-citizen and government-to-government relationships. Both offer opportunities and challenges. Assessment of a public health agencys readiness for digital government includes examination of technical, manage...

Governance of Higher Education--Implementation of Project Governance

Science.gov (United States)

Macheridis, Nikos

2017-01-01

This article focuses on coordination between governance actors in higher education. The object of the study is a department at a public university, seen as a multi-project environment. The purpose of this article is to illustrate and analyze project governance as a tool that allows departmental management to coordinate with the authorities, the…

The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

Directory of Open Access Journals (Sweden)

Robert Drynda

2018-02-01

Full Text Available Background/Aims: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy. Methods: Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18. Results: At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18. Conclusion: The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.

Carrier of Wingless (Cow), a Secreted Heparan Sulfate Proteoglycan, Promotes Extracellular Transport of Wingless

Science.gov (United States)

Chang, Yung-Heng; Sun, Yi Henry

2014-01-01

Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen. PMID:25360738

Network governance and capacity of local governments to deliver LED in Uganda

Directory of Open Access Journals (Sweden)

Rose B Namara

2016-02-01

Full Text Available This paper discusses network governance and its contribution to the capacity of local governments (LGs to deliver local economic development (LED in Uganda. Although a formal LED policy was only established in Uganda in February 2014, there have been LED-inspired practices in the past decade. Various scholars and practitioners have observed that the autonomy and capacity of LGs to deliver LED is limited, but have been hopeful that new governance strategies like network governance would increase the capacities of LGs. However, neither network governance arrangements among LGs, nor their potential to improve governance capacity, have been documented. In a case study of Kyenjojo District, this paper finds that existing network governance arrangements have been fundamental in improving financial autonomy at this LG, delivering some income to invest in LED activities, although no evidence was found of reduced transaction costs in transforming local economies. The study further reveals that network governance arrangements have not led to the development of specialised skills in regulation or law enforcement, and capacity gaps are evident amongst staff and members in understanding the private sector and how it works. On a positive note, there is clear evidence of attempts by the LG to be innovative. Based on these findings, this study recommends that LGs need to consider a multi-pronged or multi-network governance approach to LED, which in turn will require a refocusing of governance mechanisms to become more dynamic and responsive, and offer incentives to the various actors in the development sector.

High content screening for G protein-coupled receptors using cell-based protein translocation assays

DEFF Research Database (Denmark)

Grånäs, Charlotta; Lundholt, Betina Kerstin; Heydorn, Arne

2005-01-01

G protein-coupled receptors (GPCRs) have been one of the most productive classes of drug targets for several decades, and new technologies for GPCR-based discovery promise to keep this field active for years to come. While molecular screens for GPCR receptor agonist- and antagonist-based drugs...... will continue to be valuable discovery tools, the most exciting developments in the field involve cell-based assays for GPCR function. Some cell-based discovery strategies, such as the use of beta-arrestin as a surrogate marker for GPCR function, have already been reduced to practice, and have been used...... as valuable discovery tools for several years. The application of high content cell-based screening to GPCR discovery has opened up additional possibilities, such as direct tracking of GPCRs, G proteins and other signaling pathway components using intracellular translocation assays. These assays provide...

Data governance implementation concept

OpenAIRE

Ullrichová, Jana

2016-01-01

This master´s thesis discusses concept of implementation for data governance. The theoretical part of this thesis is about data governance. It explains why data are important for company, describes definitoons of data governance, its history, its components, its principles and processes and fitting in company. Theoretical part is amended with examples of data governance failures and banking specifics. The main goal of this thesis is to create a concept for implementing data governance and its...

CORPORATE GOVERNANCE – WAY OF GOVERNANCE FOR MODERN COMPANIES

Directory of Open Access Journals (Sweden)

Alina HAGIU

2016-05-01

Full Text Available Through corporate governance is aimed the building of a structure enabling a wide degree of freedom, within the law, and includes several changes of principle in accordance with international standards of transparency. A good governance within an organization mitigate risk, increase performance, pave the way towards financial markets, brings competitive goods and services on market, improves management style, show transparency towards all stakeholders and social responsibility. The lack of some mandatory rules and structures can lead to chaos in business. The paper aims to present the role and the importance of the corporate governance for modern companies, as well as the principles on which this is based. In order to do that we also identified the main ways to quantificate the level of corporate governance, including also the non-financial performance criteria used by investors to assess companies listed on stock exchange.

Smart governance for smart city

Science.gov (United States)

Mutiara, Dewi; Yuniarti, Siti; Pratama, Bambang

2018-03-01

Some of the local government in Indonesia claimed they already created a smart city. Mostly the claim based of IT utilization for their governance. In general, a smart city definition is to describe a developed urban area that creates sustainable economic development and high quality of life by excelling in multiple key; economy, mobility, environment, people, living, and government. For public services, the law guarantees good governance by setting the standard for e-government implicitly including for local government or a city. Based on the arguments, this research tries to test the condition of e-government of the Indonesian city in 34 provinces. The purpose is to map e-government condition by measuring indicators of smart government, which are: transparent governance and open data for the public. This research is departing from public information disclosure law and to correspond with the existence law. By examining government transparency, the output of the research can be used to measure the effectiveness of public information disclosure law and to determine the condition of e-government in local government in which as part of a smart city.

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

Directory of Open Access Journals (Sweden)

Henry N. Bang

2013-02-01

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

Architecture Governance: The Importance of Architecture Governance for Achieving Operationally Responsive Ground Systems

Science.gov (United States)

Kolar, Mike; Estefan, Jeff; Giovannoni, Brian; Barkley, Erik

2011-01-01

Topics covered (1) Why Governance and Why Now? (2) Characteristics of Architecture Governance (3) Strategic Elements (3a) Architectural Principles (3b) Architecture Board (3c) Architecture Compliance (4) Architecture Governance Infusion Process. Governance is concerned with decision making (i.e., setting directions, establishing standards and principles, and prioritizing investments). Architecture governance is the practice and orientation by which enterprise architectures and other architectures are managed and controlled at an enterprise-wide level

Good government and good governance: record keeping in a ...

African Journals Online (AJOL)

This article addresses the challenges that arise when record keeping systems are advocated as a necessary under-pinning for good government and good governance. The relationship between record keeping and accountability is analysed and contextualised in relation to transparency and Freedom of Information ...

Corporate Governance and Shariah Governance at Islamic Financial Institutions : Assessing from Current Practice in Malaysia

OpenAIRE

Mizushima, Tadashi; Tadashi, Mizushima

2014-01-01

The purpose of this study is to examine the relation between corporate governance and Shariah governance, and how those governance concepts are handled at Islamic financial institutions.Although using the same word “governance,” Western corporate governance and Islamic Shariah governance may be different. The main research question is how different or similar are governance at conventional banks and Shariah governance at Islamic banks? We would like to find an answer to this question by under...

Governance and organizational theory

Directory of Open Access Journals (Sweden)

Carlos E. Quintero Castellanos

2017-07-01

Full Text Available The objective of this essay is to propose a way to link the theoretical body that has been weaved around governance and organizational theory. For this, a critical exposition is done about what is the theoretical core of governance, the opportunity areas are identified for the link of this theory with organizational theory. The essay concludes with a proposal for the organizational analysis of administrations in governance. The essay addresses with five sections. The first one is the introduction. In the second one, I present a synthesis of the governance in its current use. In the next one are presented the work lines of the good governance. In the fourth part, I show the organizational and managerial limits in the governance theory. The last part develops the harmonization proposal for the governance and organizational theories.

The Development of an IT Governance Maturity Model for Hard and Soft Governance

NARCIS (Netherlands)

Smits, Daniël; van Hillegersberg, Jos; Devos, Jan; DeHaes, Steven

2014-01-01

To be able to advance in maturity, organizations should pay attention to both the hard and soft aspects of governance. Current literature on IT governance (ITG) is mostly directed at the hard part of governance, focusing on structures and processes. The soft part of governance is related to social

Governing Academic Medical Center Systems: Evaluating and Choosing Among Alternative Governance Approaches.

Science.gov (United States)

Chari, Ramya; O'Hanlon, Claire; Chen, Peggy; Leuschner, Kristin; Nelson, Christopher

2018-02-01

The ability of academic medical centers (AMCs) to fulfill their triple mission of patient care, medical education, and research is increasingly being threatened by rising financial pressures and resource constraints. Many AMCs are, therefore, looking to expand into academic medical systems, increasing their scale through consolidation or affiliation with other health care systems. As clinical operations grow, though, the need for effective governance becomes even more critical to ensure that the business of patient care does not compromise the rest of the triple mission. Multi-AMC systems, a model in which multiple AMCs are governed by a single body, pose a particular challenge in balancing unity with the needs of component AMCs, and therefore offer lessons for designing AMC governance approaches. This article describes the development and application of a set of criteria to evaluate governance options for one multi-AMC system-the University of California (UC) and its five AMCs. Based on a literature review and key informant interviews, the authors identified criteria for evaluating governance approaches (structures and processes), assessed current governance approaches using the criteria, identified alternative governance options, and assessed each option using the identified criteria. The assessment aided UC in streamlining governance operations to enhance their ability to respond efficiently to change and to act collectively. Although designed for UC and a multi-AMC model, the criteria may provide a systematic way for any AMC to assess the strengths and weaknesses of its governance approaches.

Governing environmental conflicts in China: Under what conditions do local government compromise?

NARCIS (Netherlands)

Y. Li (Yanwei); J.F.M. Koppenjan (Joop); S. Verweij (Stefan)

2016-01-01

markdownabstractIn recent years, governing environmental conflicts concerning the planning, construction, and operation of urban facilities has increasingly become a challenge for Chinese local governments. Chinese governments seek adequate responses to deal with these conflicts, for instance by

Governing environmental conflicts in China : Under what conditions do local governments compromise?

NARCIS (Netherlands)

Li, Yanwei; Koppenjan, Joop; Verweij, Stefan

2016-01-01

In recent years, governing environmental conflicts concerning the planning, construction, and operation of urban facilities has increasingly become a challenge for Chinese local governments. Chinese governments seek adequate responses to deal with these conflicts, for instance by ignoring criticism

Public management and governance

National Research Council Canada - National Science Library

Bovaird, A. G; Löffler, Elke

2009-01-01

... how the process of governing needs to be fundamentally altered if a government is to retain public trust and make better use of society's resources. Key themes covered include: ■ ■ ■ ■ the challenges and pressures which governments experience in an international context; the changing functions of modern government in the global economy; the 'mixed ec...

Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition.

Science.gov (United States)

Koel, Mariann; Võsa, Urmo; Krjutškov, Kaarel; Einarsdottir, Elisabet; Kere, Juha; Tapanainen, Juha; Katayama, Shintaro; Ingerpuu, Sulev; Jaks, Viljar; Stenman, Ulf-Hakan; Lundin, Karolina; Tuuri, Timo; Salumets, Andres

2017-09-01

Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin (HCG) and its hyperglycosylated form (HCG-H) were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes (CGA, CGB and LGALS16), induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-β/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Hard and Soft Governance

DEFF Research Database (Denmark)

Moos, Lejf

2009-01-01

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

Interoperability, Enterprise Architectures, and IT Governance in Government

OpenAIRE

Scholl , Hans ,; Kubicek , Herbert; Cimander , Ralf

2011-01-01

Part 4: Architecture, Security and Interoperability; International audience; Government represents a unique, and also uniquely complex, environment for interoperation of information systems as well as for integration of workflows and processes across governmental levels and branches. While private-sector organizations by and large have the capacity to implement “enterprise architectures” in a relatively straightforward fashion, for notable reasons governments do not enjoy such luxury. For thi...

Governance in Health – The Need for Exchange and Evidence; Comment on “Governance, Government, and the Search for New Provider Models”

Directory of Open Access Journals (Sweden)

Tata Chanturidze

2016-08-01

Full Text Available Governance in health is cited as one of the key factors in balancing the concerns of the government and public sector with the interests of civil society/private players, but often remains poorly described and operationalized. Richard Saltman and Antonio Duran look at two aspects in the search for new provider models in a context of health markets signalling liberalisation: (i the role of the government to balance public and private interests and responsibilities in delivering care through modernised governance arrangements, and (ii the finding that operational complexities may hinder well–designed provider governance models, unless governance reflects country-specific realities. This commentary builds on the discussion by Saltman and Duran, and argues that the concept of governance needs to be clearly defined and operationalized in order to be helpful for policy debate as well as for the development of an applicable framework for performance improvement. It provides a working definition of governance and includes a reflection on the prevailing cultural norms in an organization or society upon which any governance needs to be build. It proposes to explore whether the “evidence-based governance” concept can be introduced to generate knowledge about innovative and effective governance models, and concludes that studies similar to the one by Saltman and Duran can inform this debate.

Governance: Blending Bureaucratic Rules with Day to Day Operational Realities Comment on "Governance, Government, and the Search for New Provider Models".

Science.gov (United States)

Chinitz, David P

2016-05-31

Richard Saltman and Antonio Duran take up the challenging issue of governance in their article "Governance, Government and the Search for New Provider Models," and use two case studies of health policy changes in Sweden and Spain to shed light on the subject. In this commentary, I seek to link their conceptualization of governance, especially its interrelated roles at the macro, meso, and micro levels of health systems, with the case studies on which they report. While the case studies focus on the shifts in governance between the macro and meso levels and their impacts on achievement of desired policy outcomes, they also highlight the need to better integrate the dynamics of day to day operations within micro organizations into the overall governance picture. © 2016 by Kerman University of Medical Sciences.

Too difficult to govern? An assessment of the governability of transport biofuels in the EU

International Nuclear Information System (INIS)

Di Lucia, Lorenzo

2013-01-01

Transport biofuels are currently the subject of heated debate in the EU. In the past decade the deployment of these technologies has been justified by claims of attractive environmental, geopolitical and rural development benefits. However, expectations have rapidly turned into deep criticism regarding the sustainability of these technologies and the desirability of pursuing the biofuel path. This situation has generated an on-going controversy and policy deadlock at EU level. This study explores these issues from a governance perspective. Employing the concept of system governability, derived from interactive governance theory, it attempts to shed some light on the problems facing the governance of biofuels and on how the quality of the governance system could be improved. The analysis showed that the governability of the system decreased substantially in the period 2003–2012 due to increasing governing needs and decreasing governing capacity. The quality of the governance system can be improved by (i) improving governing capacity by reducing conflicts among governing actors, advancing consistency among institutions and creating capacity at international and global level; and (ii) promoting advanced technologies and adjusting societal ambitions and expectations regarding biofuels. - highlights: • Biofuels in the EU are significantly more difficult to govern today than in 2003. • This is due to the qualities of the system to be governed and the governing system. • Sustainable biofuel systems are inherently difficult to govern

Modeling structure of G protein-coupled receptors in huan genome

KAUST Repository

Zhang, Yang

2016-01-26

G protein-coupled receptors (or GPCRs) are integral transmembrane proteins responsible to various cellular signal transductions. Human GPCR proteins are encoded by 5% of human genes but account for the targets of 40% of the FDA approved drugs. Due to difficulties in crystallization, experimental structure determination remains extremely difficult for human GPCRs, which have been a major barrier in modern structure-based drug discovery. We proposed a new hybrid protocol, GPCR-I-TASSER, to construct GPCR structure models by integrating experimental mutagenesis data with ab initio transmembrane-helix assembly simulations, assisted by the predicted transmembrane-helix interaction networks. The method was tested in recent community-wide GPCRDock experiments and constructed models with a root mean square deviation 1.26 Å for Dopamine-3 and 2.08 Å for Chemokine-4 receptors in the transmembrane domain regions, which were significantly closer to the native than the best templates available in the PDB. GPCR-I-TASSER has been applied to model all 1,026 putative GPCRs in the human genome, where 923 are found to have correct folds based on the confidence score analysis and mutagenesis data comparison. The successfully modeled GPCRs contain many pharmaceutically important families that do not have previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin and Neuropeptide Y receptors. All the human GPCR models have been made publicly available through the GPCR-HGmod database at http://zhanglab.ccmb.med.umich.edu/GPCR-HGmod/ The results demonstrate new progress on genome-wide structure modeling of transmembrane proteins which should bring useful impact on the effort of GPCR-targeted drug discovery.

Fragmented International Governance of Arctic Offshore Oil : Governance Challenges and Institutional Improvement

NARCIS (Netherlands)

Humrich, Christoph

The governance architecture in the Arctic region is subject to broad public and academic debate. Existing governance arrangements are not considered sufficient to minimize risks and impacts from Arctic offshore oil activities. These governance arrangements are fragmented between law of the sea

Status of will governance in determination of law governing business documents validity

OpenAIRE

Peyman Mohammadi; Saeed Kheradmandi

2014-01-01

Law governing substantive conditions of business documents issuance is one of important problems facing investigators. Since law governing business contracts and documents is governing out of limits of national law today, value and effect of will governance is of interest to jurisprudents because contract parties are allowed to determine contract effects and terms consensually to the extent to which these effects and terms do not contradict public order and imperative law and, in fact, they c...

G Protein-Coupled Receptors in Cancer

Directory of Open Access Journals (Sweden)

Rachel Bar-Shavit

2016-08-01

Full Text Available Despite the fact that G protein-coupled receptors (GPCRs are the largest signal-conveying receptor family and mediate many physiological processes, their role in tumor biology is underappreciated. Numerous lines of evidence now associate GPCRs and their downstream signaling targets in cancer growth and development. Indeed, GPCRs control many features of tumorigenesis, including immune cell-mediated functions, proliferation, invasion and survival at the secondary site. Technological advances have further substantiated GPCR modifications in human tumors. Among these are point mutations, gene overexpression, GPCR silencing by promoter methylation and the number of gene copies. At this point, it is imperative to elucidate specific signaling pathways of “cancer driver” GPCRs. Emerging data on GPCR biology point to functional selectivity and “biased agonism”; hence, there is a diminishing enthusiasm for the concept of “one drug per GPCR target” and increasing interest in the identification of several drug options. Therefore, determining the appropriate context-dependent conformation of a functional GPCR as well as the contribution of GPCR alterations to cancer development remain significant challenges for the discovery of dominant cancer genes and the development of targeted therapeutics.

Uncovering Wnt signaling mechanisms in control of cell migration in C. elegans

NARCIS (Netherlands)

Mentink, R.A.

2014-01-01

Morphogens such as Wnt proteins play a central role in embryonic patterning by providing positional information to cells in developing tissues. In recent years, it has become clear that such morphogenic gradients also contribute to the guidance of migrating cells and axons in the developing nervous

Cloud Computing Governance Lifecycle

Directory of Open Access Journals (Sweden)

Soňa Karkošková

2016-06-01

Full Text Available Externally provisioned cloud services enable flexible and on-demand sourcing of IT resources. Cloud computing introduces new challenges such as need of business process redefinition, establishment of specialized governance and management, organizational structures and relationships with external providers and managing new types of risk arising from dependency on external providers. There is a general consensus that cloud computing in addition to challenges brings many benefits but it is unclear how to achieve them. Cloud computing governance helps to create business value through obtain benefits from use of cloud computing services while optimizing investment and risk. Challenge, which organizations are facing in relation to governing of cloud services, is how to design and implement cloud computing governance to gain expected benefits. This paper aims to provide guidance on implementation activities of proposed Cloud computing governance lifecycle from cloud consumer perspective. Proposed model is based on SOA Governance Framework and consists of lifecycle for implementation and continuous improvement of cloud computing governance model.

GPCRdb

DEFF Research Database (Denmark)

Isberg, Vignir; Mordalski, Stefan; Munk, Christian

2016-01-01

Recent developments in G protein-coupled receptor (GPCR) structural biology and pharmacology have greatly enhanced our knowledge of receptor structure-function relations, and have helped improve the scientific foundation for drug design studies. The GPCR database, GPCRdb, serves a dual role...... in disseminating and enabling new scientific developments by providing reference data, analysis tools and interactive diagrams. This paper highlights new features in the fifth major GPCRdb release: (i) GPCR crystal structure browsing, superposition and display of ligand interactions; (ii) direct deposition...... a smooth browsing experience and development. GPCRdb is available at http://www.gpcrdb.org/ and it's open source code at https://bitbucket.org/gpcr/protwis....

Integrative environmental governance: enhancing governance in the era of synergies

NARCIS (Netherlands)

Visseren-Hamakers, I.J.

2015-01-01

The issue of regime complexity in global environmental governance is widely recognized. The academic debate on regime fragmentation has itself however been rather fragmented, with discussions circling around different concepts, including inter-organizational relations, polycentric governance,

A Primer on E-Government: Sectors, Stages, Opportunities, and Challenges of Online Governance

National Research Council Canada - National Science Library

Seifert, Jeffrey W

2003-01-01

...), public access to government information, service delivery, and information security. E-government solutions are prominently represented in efforts to improve the management and efficiency of government information technology resources...

Chemogenomic analysis of G-protein coupled receptors and their ligands deciphers locks and keys governing diverse aspects of signalling.

Directory of Open Access Journals (Sweden)

Jörg D Wichard

Full Text Available Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic or inhibitory (antagonistic ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences.

E-Government Maturity Model for Sustainable E-Government Services from the Perspective of Developing Countries

Directory of Open Access Journals (Sweden)

Pusp Raj Joshi

2018-06-01

Full Text Available Electric government (e-government projects in developing countries are facing many challenges to deliver sustainable e-government services. From the existing literature, we found that most of the studies considered lack of technology, and limitations in budgets and human resources as the main hurdles in effective implementation of e-government services. Along with these limitations, we found that the e-government maturity models adopted by developing countries are failing to provide an appropriate strategic plan to deploy sustainable e-government services. While assessing the existing e-government maturity model, we made several observations on the lack of detail, the technology-centric nature, the emphasis on implementation, and the lack of an adoption strategy. This work contributes toward the proposition of a new e-government maturity model that would address the limitations of exiting e-government maturity models, and would support governments in developing countries to achieve sustainable e-government services. To achieve this goal, we considered five determinants—a detailed process, streamlined services, agile accessibility, use of state-of-the-art technology, and trust and awareness. The proposed model was validated by employing an empirical investigation through case-study and survey methods. We found that both the implementers (government and adopters (users of the e-government services benefited from the proposed model, resulting in an increased sustainability of e-government services.

The politics of meta-governance in transnational private sustainability governance

NARCIS (Netherlands)

Fransen, L.

2015-01-01

In order to address challenges resulting from interactions between transnational private sustainability standard organizations, initiatives emerge that meta-govern these standards. Contrary to prevailing understandings in public policy literature, such meta-governance initiatives are mostly run by

Data governance tools evaluation criteria, big data governance, and alignment with enterprise data management

CERN Document Server

Soares, Sunil

2015-01-01

Data governance programs often start off using programs such as Microsoft Excel and Microsoft SharePoint to document and share data governance artifacts. But these tools often lack critical functionality. Meanwhile, vendors have matured their data governance offerings to the extent that today's organizations need to consider tools as a critical component of their data governance programs. In this book, data governance expert Sunil Soares reviews the Enterprise Data Management (EDM) reference architecture and discusses key data governance tasks that can be automated by tools for business glossa

Innovation in City Governments

DEFF Research Database (Denmark)

Lewis, Jenny M; Ricard, Lykke Margot; Klijn, Erik Hans

Innovation has become an important focus for governments around the world over the last decade, with greater pressure on governments to do more with less, and expanding community expectations. Some are now calling this ‘social innovation’ – innovation that is related to creating new services...... that have value for stakeholders (such as citizens) in terms of the social and political outcomes they produce. Innovation in City Governments: Structures, Networks, and Leadership establishes an analytical framework of innovation capacity based on three dimensions: Structure - national governance...... project in Copenhagen, Barcelona and Rotterdam. The book provides major new insights on how structures, networks and leadership in city governments shape the social innovation capacity of cities. It provides ground-breaking analyses of how governance structures and local socio-economic challenges...

Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications

Science.gov (United States)

Cvicek, Vaclav; Goddard, William A.; Abrol, Ravinder

2016-01-01

The understanding of G-protein coupled receptors (GPCRs) is undergoing a revolution due to increased information about their signaling and the experimental determination of structures for more than 25 receptors. The availability of at least one receptor structure for each of the GPCR classes, well separated in sequence space, enables an integrated superfamily-wide analysis to identify signatures involving the role of conserved residues, conserved contacts, and downstream signaling in the context of receptor structures. In this study, we align the transmembrane (TM) domains of all experimental GPCR structures to maximize the conserved inter-helical contacts. The resulting superfamily-wide GpcR Sequence-Structure (GRoSS) alignment of the TM domains for all human GPCR sequences is sufficient to generate a phylogenetic tree that correctly distinguishes all different GPCR classes, suggesting that the class-level differences in the GPCR superfamily are encoded at least partly in the TM domains. The inter-helical contacts conserved across all GPCR classes describe the evolutionarily conserved GPCR structural fold. The corresponding structural alignment of the inactive and active conformations, available for a few GPCRs, identifies activation hot-spot residues in the TM domains that get rewired upon activation. Many GPCR mutations, known to alter receptor signaling and cause disease, are located at these conserved contact and activation hot-spot residue positions. The GRoSS alignment places the chemosensory receptor subfamilies for bitter taste (TAS2R) and pheromones (Vomeronasal, VN1R) in the rhodopsin family, known to contain the chemosensory olfactory receptor subfamily. The GRoSS alignment also enables the quantification of the structural variability in the TM regions of experimental structures, useful for homology modeling and structure prediction of receptors. Furthermore, this alignment identifies structurally and functionally important residues in all human GPCRs

Governing Knowledge: The Formalization Dilemma in the Governance of the Public Sciences

Science.gov (United States)

Woelert, Peter

2015-01-01

This paper offers a conceptually novel contribution to the understanding of the distinctive governance challenges arising from the increasing reliance on formalized knowledge in the governance of research activities. It uses the current Australian research governance system as an example--a system which exhibits a comparatively strong degree of…

Voluntary Environmental Governance Arrangements

NARCIS (Netherlands)

van der Heijden, J.

2012-01-01

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

Beyond Good Governances: Lesson from Forest and Cultural Governance in Pelalawan, Pangkalan Kerinci, Riau

Directory of Open Access Journals (Sweden)

Novi Paramita Dewi

2017-11-01

Full Text Available The shift in government concept into governance takes the consequence of changes in public governance including in the forestry sector. Good forest governance becomes a great hope for managing the forest condition so that sustainable forest management can be realized. However, in its implementation, it contains a big challenge for the forest in Indonesia which is mostly identical with indigenous people. Meanwhile, the development becomes a necessity that cannot be inhibited in which business corporation as the actor who plays in the forest governance is considered as a major threat to the environment and indigenous people. To achieve good forest governance, it is necessary to have a synergy with cultural governance that is hoped to be able to accommodate the indigenous people interests. This paper is a case study related to the practice as an effort to achieve good forest governance in the indigenous people of Pelalawan that are followed by the cultural governance effort so that the indigenous people culture of Pelalawan that is closely related to the forest can still be maintained.

Digital government and public health.

Science.gov (United States)

Fountain, Jane E

2004-10-01

Digital government is typically defined as the production and delivery of information and services inside government and between government and the public using a range of information and communication technologies. Two types of government relationships with other entities are government-to-citizen and government-to-government relationships. Both offer opportunities and challenges. Assessment of a public health agency's readiness for digital government includes examination of technical, managerial, and political capabilities. Public health agencies are especially challenged by a lack of funding for technical infrastructure and expertise, by privacy and security issues, and by lack of Internet access for low-income and marginalized populations. Public health agencies understand the difficulties of working across agencies and levels of government, but the development of new, integrated e-programs will require more than technical change - it will require a profound change in paradigm.

Systems approach to waste governance: unpacking the challenges facing local government

CSIR Research Space (South Africa)

Godfrey, Linda K

2008-09-01

Full Text Available and Tourism (DEAT, 2007) highlighted the obstacles that are faced by local government in achieving service delivery for waste. The three identified obstacles included Financial Capacity; Institutional Capacity; Technical Capacity. 2 Opportunity cost... the systems diagrams show (Figure 2), is that without intervention by national government departments, e.g. National Treasury, Department of Provincial and Local Government, or Department of Environmental Affairs and Tourism, municipalities will be unable...

Developing digital forensic governance

CSIR Research Space (South Africa)

Grobler, M

2010-03-01

Full Text Available This paper presents a Digital Forensic (DF) governance framework and its mapping on the SANS ISO/IEC 38500:2009 Corporate governance of information technology structure. DF governance assists organisations in guiding the management team...

Federalism and multilevel governance

NARCIS (Netherlands)

van der Wusten, H.; Agnew, J.; Mamadouh, V.; Secor, A.J.; Sharp, J.

2015-01-01

Federalism and multilevel governance both emphasize polycentricity in governing arrangements. With their different intellectual pedigrees, these concepts are discussed in two separate sections. Fragments are now increasingly mixed up in hybrid forms of governance that also encompass originally

Regulatory Governance

DEFF Research Database (Denmark)

Kjær, Poul F.; Vetterlein, Antje

2018-01-01

Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

Corporate Governance Country Assessment : Malaysia

OpenAIRE

World Bank

2012-01-01

This report assesses Ghana s corporate governance policy framework. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Ghana. It is an update of the 2005 Corporate Governance ROSC. Good corporate governance enhances investor trust, helps to protects mino...

Structural basis for activation of G-protein-coupled receptors

DEFF Research Database (Denmark)

Gether, Ulrik; Asmar, Fazila; Meinild, Anne Kristine

2002-01-01

into conformational changes accompanying GPCR activation and the underlying molecular mechanism governing transition of the receptor between its active and inactive states. Using the beta2-adrenergic receptor as a model system we have obtained evidence for an evolutionary conserved activation mechanism where...... changes and receptor activation. At the current stage we are exploring the possibility of reaching this goal by direct in situ labeling of the beta2-adrenergic receptor in Xenopus laevis oocytes with conformationally sensitive fluorescent probes and parallel detection of receptor activation by co...

Governance: Blending Bureaucratic Rules with Day to Day Operational Realities; Comment on “Governance, Government, and the Search for New Provider Models”

Directory of Open Access Journals (Sweden)

David P Chinitz

2016-09-01

Full Text Available Richard Saltman and Antonio Duran take up the challenging issue of governance in their article “Governance, Government and the Search for New Provider Models,” and use two case studies of health policy changes in Sweden and Spain to shed light on the subject. In this commentary, I seek to link their conceptualization of governance, especially its interrelated roles at the macro, meso, and micro levels of health systems, with the case studies on which they report. While the case studies focus on the shifts in governance between the macro and meso levels and their impacts on achievement of desired policy outcomes, they also highlight the need to better integrate the dynamics of day to day operations within micro organizations into the overall governance picture.

Adopting service governance governing portfolio value for sound corporate citzenship

CERN Document Server

AXELOS, AXELOS

2015-01-01

Adopting Service Governance provides a useful umbrella for a number of frameworks including ITIL®, TOGAF®, COBIT®, ITSM, BSM, Business Analysis, Programme Management, Management of Value, Management of Portfolios and Management of Risk by establishing the top-down governance of an organisation through services.

RE-ENGINEERING GOVERNANCE; E-GOVERNMENT AS A TOOL FOR DECENTRALIZATION; GHANA AS A CASE STUDY

DEFF Research Database (Denmark)

Gyaase, Patrick Ohemeng Kwadwo

This research was undertaken to study the diffusion of E-government as a tool for decentralization, using Ghana as a case study. E-governance has been credited with the potency of facilitating good governance in countries with appreciable level of E-government maturity. Much attention is being...... espoused by E-government. This research therefore assesses the diffusion of E-government as a tool for decentralization in Ghana. The research was carried out using mixed-methods and was approached from four theoretical perspectives namely Innovation Diffusion theory the TOE framework for technological....... Qualitative data was used to assess the factors affecting the diffusion of e-government as a tool for decentralization and the results pointed to vendor and donor led diffusion as affecting E-government implementation. There is also the absence of convergence between the E-government, the decentralization...

Government and Business

DEFF Research Database (Denmark)

Campbell, John L.

2015-01-01

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

Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models.

Directory of Open Access Journals (Sweden)

Catherine L Worth

Full Text Available BACKGROUND: Up until recently the only available experimental (high resolution structure of a G-protein-coupled receptor (GPCR was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. METHODOLOGY: We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s for building a comparative molecular model. CONCLUSIONS: The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying

Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models.

Science.gov (United States)

Worth, Catherine L; Kleinau, Gunnar; Krause, Gerd

2009-09-16

Up until recently the only available experimental (high resolution) structure of a G-protein-coupled receptor (GPCR) was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s) to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s) for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s) for building a comparative molecular model. The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying suitable templates for GPCR homology modelling that will

The Knowledge Governance Approach

DEFF Research Database (Denmark)

Foss, Nicolai J.

with diverse capabilities of handling these transactions. Various open research issues that a knowledge governance approach may illuminate are sketched. Although knowledge governance draws clear inspiration from organizational economics and `rational' organization theory, it recognizes that knowledge......An attempt is made to characterize a `knowledge governance approach' as a distinctive, emerging field that cuts across the fields of knowledge management, organisation studies, strategy and human resource management. Knowledge governance is taken up with how the deployment of administrative...

'Governance' sebagai Pengelolaan Konflik

Directory of Open Access Journals (Sweden)

Riza Noer Arfani

2005-03-01

Full Text Available The article explores the notion of understanding governance as part of conflict management, or vice versa, of undustanding conflict management aspects as benefiting from governance concepts and practices. Governance, with its much broader meaning than government, suggests diverse relevant and significant clues, hints and ideas in the context of conflict management endeavors. one of which is the idea to involve larger audiences and stakeholders –beyond the conventional institutions such as governmental bodies– in policy making processes and public discourses. Such comprehension and appreciation of governance concepts and practices is certainly parallel with the conflict management philosophies, concepis and practices which based on and oriented toward integrative, non-formal and non-litigative mechanisms.

Foresight as an e-Government Development Planning Component: Proposed e-Government Foresight Framework

Directory of Open Access Journals (Sweden)

Rokas Grincevičius

2012-07-01

Full Text Available Despite the fact that e-government is developed by a country which is making the first steps in this area, or state, seeking to increase effectiveness of the existing e-government tools, it is necessary to have the methodology to create a basis for the formation of strategic e-government decisions, whose implementation will meet existing citizen needs and emerged challenges which appear during continuous information communication technology transformation processes.One of the ways to respond to these requirements is the application of foresight exercises as a component of strategic e-government planning. Nevertheless in Lithuania and many other Eastern European countries, the planning process is still centralized, based on the five-year planning context. Ex communist states are behind other regions with the number of research based on the foresight methodology, so these conditions determine the lack of information in this domain and this article is a small part of the attempt to fill the existing vacuum.The main aim of this article is to analyse the foresight impact on the electronic government strategic planning process, its role in the political decision formation process and by identifying contact points of different foresight research components, in the context of e-government foresight methodology framework creation processes, to form a deeper perception on how foresight works as a system.This aim is determined by the following objectives—to analyse foresight concept, circumstances and causes of its origin, main guidelines, methods used during foresight exercises and reasons, which determine its application; also, to analyse different suggested foresight exercise approaches and according to the results of the analysis, to form a distinctive e-government foresight methodology, which can be used for already performed foresight analysis or for prototyping a planned one.Thus, the first part of the article covers the most important theoretical

Tax Governance

DEFF Research Database (Denmark)

Boll, Karen; Brehm Johansen, Mette

to wider international trends within tax administration, especially concerning the development of risk assessments and internal control in the corporations and a greater focus on monitoring of these elements by the tax authorities. Overall, the working paper concludes that Tax Governance as a model......This working paper presents an analysis of the experiences of Cooperative Compliance in Denmark. Cooperative Compliance denotes a specific kind of collaborative program for the regulation of large corporate taxpayers by the tax authorities. Cooperative Compliance programs have been implemented...... in several countries worldwide. In Denmark the program is called Tax Governance. Tax Governance has been studied using qualitative method and the analyses of the working paper build on an extensive base of in-depth interviews – primarily with tax directors from corporations participating in the program...

Governance, resource curse and donor

OpenAIRE

Wiig, Arne

2008-01-01

Plan Part 1. Governance What is good governance? Why is it important? How can we measure good governance? Part 2. The resource curse and the importance of governance in resource rich countries Focus on political economy (PE) models of the resource curse Policy implications Some donor initiatives Transparency and the EITI Petroleum related aid - Window dressing initiatives or research based? Conclusion Governance, resource curse and donor

Cities, Europeanization and Multi-level Governance: Governing Climate Change through Transnational Municipal Networks

NARCIS (Netherlands)

Kern, K.; Bulkeley, H.

2009-01-01

This article focuses on a variant of multi-level governance and Europeanization, i.e. the transnational networking of local authorities. Focusing on local climate change policy, the article examines how transnational municipal networks (TMNs) govern in the context of multi-level European governance.

Result-Based Public Governance

DEFF Research Database (Denmark)

Boll, Karen

Within the public sector, many institutions are either steered by governance by targets or result-based governance. The former sets up quantitative internal production targets, while the latter advocates that production is planned according to outcomes which are defined as institution-produced ef......Within the public sector, many institutions are either steered by governance by targets or result-based governance. The former sets up quantitative internal production targets, while the latter advocates that production is planned according to outcomes which are defined as institution......-produced effects on individuals or businesses in society; effects which are often produced by ‘nudging’ the citizenry in a certain direction. With point of departure in these two governance-systems, the paper explores a case of controversial inspection of businesses’ negative VAT accounts and it describes...... explores how and why this state of affairs appears and problematizes the widespread use of result-based governance and nudging-techniques by public sector institutions....

Enhanced governance committees in South Africa’s national government departments: A conceptual exploration

Directory of Open Access Journals (Sweden)

Tankiso Moloi

2015-04-01

Full Text Available This paper argues that almost all other non-governmental institutions for instance banks and pension funds, in addition to the risk and audit committees, have credit committees in respect of banks and investment committees in respect of pension funds. These committees provide oversight on the core businesses of these institutions. In a similar manner, national government departments should not only have universal governance committees such as the audit and risk committees, instead the study envisions governance committees modelled around the idea parliamentary portfolio committees. The envisaged committees will remain governance committees with defined roles and responsibilities similar to the audit and risk committees that are already in existence in the national government departments.

Climate change governance

Energy Technology Data Exchange (ETDEWEB)

Knieling, Joerg [HafenCity Univ. Hamburg (Germany). Urban Planning and Regional Development; Leal Filho, Walter (eds.) [HAW Hamburg (Germany). Research and Transfer Centre Applications of Life Science

2013-07-01

Climate change is a cause for concern both globally and locally. In order for it to be tackled holistically, its governance is an important topic needing scientific and practical consideration. Climate change governance is an emerging area, and one which is closely related to state and public administrative systems and the behaviour of private actors, including the business sector, as well as the civil society and non-governmental organisations. Questions of climate change governance deal both with mitigation and adaptation whilst at the same time trying to devise effective ways of managing the consequences of these measures across the different sectors. Many books have been produced on general matters related to climate change, such as climate modelling, temperature variations, sea level rise, but, to date, very few publications have addressed the political, economic and social elements of climate change and their links with governance. This book will address this gap. Furthermore, a particular feature of this book is that it not only presents different perspectives on climate change governance, but it also introduces theoretical approaches and brings these together with practical examples which show how main principles may be implemented in practice.

Ambidextrous IT Governance

DEFF Research Database (Denmark)

Andersen, Peter; Svejvig, Per; Tordrup Heeager, Lise

2017-01-01

Through a case study at a global technology company, we investigate how organizations can adapt their IT governance approach to the information system at hand. This is done by considering the degree of information system integration and whether the system is related to supporting operational...... efficiency (exploitation) or innovation (exploration). Based on the findings of the case study, we introduce the concept of ambidextrous IT governance to describe how IT governance can be adapted to fit the dual needs of both exploration and exploitation through the use of IS....

Institutionalizing Global Governance

DEFF Research Database (Denmark)

Rasche, Andreas; Gilbert, Dirk Ulrich

2012-01-01

The United Nations Global Compact – which is a Global Public Policy Network advocating 10 universal principles in the areas of human rights, labor standards, environmental protection, and anticorruption – has turned into the world's largest corporate responsibility initiative. Although the Global...... Compact is often characterized as a promising way to address global governance gaps, it remains largely unclear why this is the case. To address this problem, we discuss to what extent the initiative represents an institutional solution to exercise global governance. We suggest that new governance modes...

Dawn of e-government

DEFF Research Database (Denmark)

Henriksen, Helle Zinner; Damsgaard, Jan

2007-01-01

Most countries have defined strategies for e-government. The objectives for implementing e-government are often defined but the means for fuelling the adoption and diffusion of e-government are typically less well clear in the policy statements. The present study assesses the impact of latest...... internally and externally. The e-Day initiative represents a drastic change in the former policy statements concerning IT adoption and diffusion in Danish government. The policy statements had previously been based on voluntary adoption focusing on visions and pedagogical intervention in governmental...

Exploring Knowledge Governance

DEFF Research Database (Denmark)

Foss, Nicolai Juul; Mahoney, Joseph T

Knowledge governance is characterized as a distinctive research subject, the understanding of which cuts across diverse fields in management. In particular, it represents an intersection of knowledge management, strategic management, and theories of the firm. Knowledge governance considers how de...

Making Government Liquid

DEFF Research Database (Denmark)

du Gay, Paul; Millo, Yuval; Tuck, Penelope

2012-01-01

The financialised character of contemporary rationalities of public governance has been the subject of increased attention within a range of disciplinary and interdisciplinary fields. With this paper we propose a particular analytical framework, focused on the notion of 'governance devices', for ...

Local Government Internal Audit Compliance

Directory of Open Access Journals (Sweden)

Greg Jones

2015-09-01

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

A new corporate governance

Directory of Open Access Journals (Sweden)

Ion Bucur

2015-12-01

Full Text Available The issue of corporate governance has become increasingly important as globalisation has begun to accelerate and the economic and financial turmoil have intensified. Post-crisis context has imposed the need to expand the prospects for analysis over governance and companies, as well as the need to identify new ways of administration and resource management. From this perspective, the author aims to highlight the conditions, factors and events that have generated profound changes within the business environment, while the analysis is focusing on contemporary changes in the systems of corporate governance and economic mutations, especially in terms of the companies. The establishment of new governance rules is demanding a theoretical approach based on new methodological requirements which are needed to reform theoretical foundations and to promote creative and effective shapes and governance systems.

DOD Open Government

Science.gov (United States)

increase transparency and openness. We encourage you to explore other information on our website to learn Defense Search DOD Open Government: Home Open Government @ DoD Transparency Congressional Inquiries IT Dashboard.gov Regulations.gov Challenge.gov Performance.gov ForeignAssistance.gov Transparency

Government Risk-Bearing

CERN Document Server

1993-01-01

The u.s. government bulks large in the nation's financial markets. The huge volume of government-issued and -sponsored debt affects the pricing and volume ofprivate debt and, consequently, resource allocation between competing alternatives. What is often not fully appreciated is the substantial influence the federal government wields overresource allocation through its provisionofcreditandrisk-bearing services to the private economy. Because peopleand firms generally seekto avoid risk, atsomeprice they are willing to pay another party to assume the risk they would otherwise face. Insurance companies are a class of private-sector firms one commonly thinks of as providing these services. As the federal government has expanded its presence in the U.S. economy during this century, it has increasingly developed programs aimed at bearing risks that the private sector either would not take on at any price, or would take on but atapricethoughtto besogreatthatmostpotentialbeneficiarieswouldnotpurchase the coverage. To...

Project governance: "Schools of thought"

Directory of Open Access Journals (Sweden)

Michiel Christiaan Bekker

2014-02-01

Full Text Available The terminology, definition and context of project governance have become a focal subject for research and discussions in project management literature. This article reviews literature on the subject of project governance and categorise the arguments into three schools of thought namely the single-firm school, multi-firm school and large capital school. The single-firm school is concerned with governance principles related to internal organisational projects and practice these principles at a technical level. The multi-firm school address the governance principles concerned with two of more organisations participating on a contractual basis on the same project and focus their governance efforts at the technical and strategic level. The large capital school consider projects as temporary organisations, forming their own entity and establishing governance principles at an institutional level. From these schools of thought it can be concluded that the definition of project governance is dependent on the type of project and hierarchical positioning in the organisation. It is also evident that further research is required to incorporate other governance variables and mechanisms such as transaction theory, social networks and agency theory. The development of project governance frameworks should also consider the complexity of projects spanning across international companies, across country borders and incorporating different value systems, legal systems, corporate governance guidelines, religions and business practices.

Responsibility with accountability: A FAIR governance framework for performance accountability of local governments

Directory of Open Access Journals (Sweden)

Anwar Shah

2014-12-01

Full Text Available This paper focuses on the role of local governments in bringing about fair, accountable, incoorruptible and responsive (FAIR governance. Local governments around the world have done important innovations to earn the trust of their residents and their comparative performance is of great interest yet a comprehensive framework to provide such benchmarking is not available. This paper attempts to fill this void, by developing a general framework for performance accountability of local governments and by relating real world practices to aspects of this framework. The proposed rating framework requires several types of assessments: (a their compliance with due process and law; (b monitoring of fiscal health for sustainability; (c monitoring of service delivery ; and (d citizens’ satisfaction with local services. The approach yields key indicators useful for benchmarking performance that can be used in selfevaluation and improvement of performance. t From an analysis of practices in local government performance monitoring and evaluation, the paper concludes that ad hoc ad-on self standing monitoring and evaluation systems are more costly and less useful than built-in tools and mechanisms for government transparency, self–evaluation and citizen based accountability such as local government output budgeting and output based fiscal transfers to finance local services.

E-Governance Frameworks - Agenda Ahead

Directory of Open Access Journals (Sweden)

Nityesh BHATT

2007-01-01

Full Text Available Electronic governance may be defined as the delivery of the government services and information to the public using electronic means. Use of IT in the government facilitates an efficient, speedy and transparent process for disseminating information to the public and other agencies, and for performing the government administration activities.

The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation

KAUST Repository

Gaffney, E. A.

2013-10-01

© The authors 2013. Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting for time delays associated with gene expression, reveals aberrant behaviours that are not consistent with early developmental self-organization, especially the requirement for exquisite temporal control. Attempts to reconcile the interpretation of Turing\\'s ideas with an increasing understanding of the mechanisms driving zebrafish pigmentation suggests that one should reconsider Turing\\'s model in terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106, 8429-8434; Yamaguchi et al., 2007, PNAS, 104, 4790-4793). Here the dynamics of pigment cells is subject to response delays implicit in the cell cycle and apoptosis. Hence we explore simulations of fish skin patterning, focussing on the dynamical influence of gene expression delays in morphogen-based Turing models and response delays for cell-based Turing models. We find that reconciling the mechanisms driving the behaviour of Turing systems with observations of fish skin patterning remains a fundamental challenge.

Governing through standards

DEFF Research Database (Denmark)

Brøgger, Katja

This abstract adresses the ways in which new education standards have become integral to new modes of education governance. The paper explores the role of standards for accelerating the shift from national to transnational governance in higher education. Drawing on the case of higher education...

Governance, Trust and Taxes

DEFF Research Database (Denmark)

Weihe, Guri; Joensen, E. Juanna Schröter

This paper examines the role of social capital (trust) vis-à-vis the propensity of a country to be a tax haven. The empirical analysis corroborates that better governed countries have a higher ceteris paribus probability to be tax havens. However, social capital counteracts the effect of governance...... quality. This effect is so strong that the partial effect of governance quality is reversed for countries with the trust index in the top quartile – making these high trust countries less likely to be tax havens – even as governance quality is increased. Thus it is crucial to consider the interaction...

GOVERNANCE FROM BELOW A Theory of Local Government With Two Empirical Tests

OpenAIRE

Jean-Paul Faguet

2005-01-01

I examine decentralization through the lens of the local dynamics that it unleashes. The national effects of decentralization are simply the sum of its local-level effects. Hence to understand decentralization we must first understand how local government works. This paper proposes a theory of local government as the confluence of two quasi-markets and one organizational dynamic. Good government results when these three elements - political, economic and civil - are in rough balance, and acto...

Lean government: Critical success factors for XBRL-based business-to-government reporting

OpenAIRE

Bharosa, N.; De Winne, C.P.I.; Van Wijk, R.; Janssen, M.F.W.H.A.

2012-01-01

Lean government is all about doing better with less through the use of ICT and the realisation of process improvements. The recently introduced eXtensible Business Reporting Language (XBRL) has shown some initial success in realising lean government. Once data is stored in XBRL format, businesses can transmit it electronically to government for reporting purposes. For businesses, XBRL will increase both corporate accountability and transparency by reducing the time needed to collect, structur...

Institutional analysis of health system governance.

Science.gov (United States)

Abimbola, Seye; Negin, Joel; Martiniuk, Alexandra L; Jan, Stephen

2017-11-01

It is important that researchers who study health system governance have a set of collective understandings of the meanings of governance, which can then inform the methods used in research. We present an institutional framing and definition of health system governance; that is, governance refers to making, changing, monitoring and enforcing the rules that govern the demand and supply of health services. This pervasive, relational view of governance is to be preferred to approaches that focus primarily on structures of governments and health care organizations, because health system governance involves communities and service users, and because governments in many low- and middle-income countries tend to under-govern. Therefore, the study of health system governance requires institutional analysis; an approach that focuses not only on structures, but also on the rules (both formal and informal) governing demand and supply relations. Using this 'structure-relations' lens, and based on our field experience, we discuss how this focus could be applied to the three approaches to framing and studying health system governance that we identified in the literature. In order of decreasing focus on structures ('hardware') and increasing focus on relations ('software'), they are: (1) the government-centred approach, which focuses on the role of governments, above or to the exclusion of non-government health system actors; (2) the building-block approach, which focuses on the internal workings of health care organizations, and treats governance as one of the several building blocks of organizations; and (3) the institutional approach, which focuses on how the rules governing social and economic interactions are made, changed, monitored and enforced. Notably, either or both qualitative and quantitative methods may be used by researchers in efforts to incorporate the analysis of how rules determine relations among health system actors into these three approaches to health system

Comparative Study of Government and Non Government College Teachers in Relation to Job Satisfaction and Job Stress

Science.gov (United States)

Kaur, Sarbjit; Kumar, Dinesh

2008-01-01

They studied on the government non government college teachers in relation to job satisfaction and job stress. They collected the sample from 200 college teacher from government and non government from bathinda district (Punjab) to discover the difference between government and non government male and female college teachers in relation to job…

Corporate Governance and Shareholder Litigation

OpenAIRE

Kalchev, Georgi

2009-01-01

The probability for shareholder litigation is studied and how corporate governance characteristics and other factors explain it. Shareholder litigation results from failure of corporate governance. Thus a better quality of corporate governance is hypothesized to decrease the litigation probability. Corporate governance index is constructed based on principal components. It is found to be a significant predictor of shareholder litigation.

COMPARATIVE STUDY ON CORPORATE GOVERNANCE

Directory of Open Access Journals (Sweden)

Gavrea Corina

2011-12-01

Full Text Available Corporate governance is a key element of today’s economic reality being more and more present in many countries around the world. This paper has two main objectives. The first one is to offer more insight into the concept of corporate governance by a thorough literature review and by presenting and analyzing a framework of corporate governance. The second objective of this paper is to investigate the corporate governance situation in three developing economies (Romania, Bulgaria and Hungary. The World Bank and the European Bank for Reconstruction and Development published a series of reports on corporate governance. The present study uses data from these reports in order to illustrate how these developing economies are dealing with corporate governance. Based on ROSC Reports a corporate governance score was calculated. As this score shows, there is room for improvement for all three developing economies. This study is important because it shows the differences in corporate governance among developing economies and the need to study these nations at the individual country level. Corporate governance has many benefits for developing economies. It helps developing economies to register sustainable growth rates, to increases investors’ confidence in the national economy, and to increase the ability of capital markets to mobilize savings.

The democratizing impact of governance networks

DEFF Research Database (Denmark)

Sørensen, Eva; Torfing, Jacob

2018-01-01

impact of governance networks. It claims that the initial celebration of the pluralization of public governance and the subsequent call for a democratic anchorage of governance networks should give way to a new concern for how governance networks can strengthen and democratize political leadership. Tying......Initially, governance networks were intended as tools for making public governance more effective. Yet, scholars have argued that governance networks also have the potential to democratize public governance. This article provides an overview of theoretical arguments pertaining to the democratizing...... political leadership to networked processes of collaborative governance fosters ‘interactive political leadership’. The article presents theoretical arguments in support of interactive political leadership, and provides an illustrative case study of a recent attempt to strengthen political leadership...

A comparative analysis between France and Japan on local governments' involvement in nuclear safety governance

International Nuclear Information System (INIS)

Sugawara, Shin-etsu; Shiroyama, Hideaki

2011-01-01

This paper shows a comparative analysis between France and Japan on the way of the local governments' involvement in nuclear safety governance through some interviews. In France, a law came into force that requires related local governments to establish 'Commision Locale d'Information' (CLI), which means the local governments officially involve in nuclear regulatory activity. Meanwhile, in Japan, related local governments substantially involve in the operation of nuclear facilities through the 'safety agreements' in spite of the lack of legal authority. As a result of comparative analysis, we can point out some institutional input from French cases as follows: to clarify the local governments' roles in the nuclear regulation system, to establish the official channels of communication among nuclear utilities, national regulatory authorities and local governments, and to stipulate explicitly the transparency as a purpose of safety regulation. (author)

Digital governance and institutional change

DEFF Research Database (Denmark)

Schlæger, Jesper

2010-01-01

Coal allocation in China is a seminal case of e-government in the political economy. The empirical phenomenon of market supporting e-government has not been systematically analysed. By developing and applying a digital governance model this article examines institutional change in a case of coal...... allocation reform in China. The case shows how the central state used e-government to get rid of planning overload. Coal allocation meetings were abolished in favour of an ecology of online market solutions. The findings suggest that further research on Chinese e-government would benefit from attention...

The Marketplace and Electronic Government Information.

Science.gov (United States)

Love, James P.

1992-01-01

Discusses the economic impact of government-produced electronic information. Examples of government prices for electronic information products are given; the debate over the privatization of government information dissemination is addressed, including examples from various government agencies; government bulletin board services are described; and…

'Pop-Up' Governance: developing internal governance frameworks for consortia: the example of UK10K.

Science.gov (United States)

Kaye, Jane; Muddyman, Dawn; Smee, Carol; Kennedy, Karen; Bell, Jessica

2015-01-01

Innovations in information technologies have facilitated the development of new styles of research networks and forms of governance. This is evident in genomics where increasingly, research is carried out by large, interdisciplinary consortia focussing on a specific research endeavour. The UK10K project is an example of a human genomics consortium funded to provide insights into the genomics of rare conditions, and establish a community resource from generated sequence data. To achieve its objectives according to the agreed timetable, the UK10K project established an internal governance system to expedite the research and to deal with the complex issues that arose. The project's governance structure exemplifies a new form of network governance called 'pop-up' governance. 'Pop-up' because: it was put together quickly, existed for a specific period, was designed for a specific purpose, and was dismantled easily on project completion. In this paper, we use UK10K to describe how 'pop-up' governance works on the ground and how relational, hierarchical and contractual governance mechanisms are used in this new form of network governance.

Privacy and Open Government

Directory of Open Access Journals (Sweden)

Teresa Scassa

2014-06-01

Full Text Available The public-oriented goals of the open government movement promise increased transparency and accountability of governments, enhanced citizen engagement and participation, improved service delivery, economic development and the stimulation of innovation. In part, these goals are to be achieved by making more and more government information public in reusable formats and under open licences. This paper identifies three broad privacy challenges raised by open government. The first is how to balance privacy with transparency and accountability in the context of “public” personal information. The second challenge flows from the disruption of traditional approaches to privacy based on a collapse of the distinctions between public and private sector actors. The third challenge is that of the potential for open government data—even if anonymized—to contribute to the big data environment in which citizens and their activities are increasingly monitored and profiled.

THE SEMANTICS OF GOVERNANCE. (The common thread running through corporate, public, and global governance.)

OpenAIRE

Rodolfo Apreda

2003-01-01

This paper argues that the semantics of governance illustrates connections and provides a unifying view from which to understand much better its natural branches: corporate, public and global governance. In this regard, governance is presented from the point of view of a distinctive field of learning and practice. Further, three levels of analysis are carried out to drive the subject home. Firstly, it highlights the extent of corporate governance within an institutional framework, and also gi...

Governing the Nexus for Sustainability

Directory of Open Access Journals (Sweden)

Marx Sina

2015-01-01

Full Text Available This report summarizes the challenges of and requirements for effective governance of the water, energy and food nexus. With global dynamics such as climate change, urbanization and changing consumption patterns, governing resources in a coherent manner becomes both more complex and more relevant for sustainable development. Governance challenges include nexus economics (costs and benefits of different approaches to resource management, institutional design (like questions of how decision-making should be best distributed and good governance (how to make sure that nexus governance adheres to certain agreed upon principles and values. In terms of economics, a balance between sector specific actions and nexus governance is required. For effective decision-making it is important that power among different institutions is both distributed and coordinated. Good nexus governance requires targets that can be monitored to make sure that basic principles are followed and to examine whether progress toward sustainable development is being made.

Corporate Governance Scorecards : Assessing and Promoting the Implementation of Codes of Corporate Governance

OpenAIRE

International Finance Corporation

2014-01-01

This is a supplement to second IFC's toolkit: developing Corporate Governance codes of best practice. The focus of second toolkit is the development of codes of corporate governance. This supplement focuses narrowly on how to use scorecards to measure the observance and implementation of such codes. It does not cover the full panoply of governance assessment tools. This supplement provides...

Tension-filled Governance?

DEFF Research Database (Denmark)

Celik, Tim Holst

on the statesituated tension-filled functional relationship between legitimation and accumulation, the study both historically and theoretically reworks this approach and reapplies it for the post-1970s/1990s governance period. It asks whether and to what extent governance has served as a distinctive post- 1970s/1990s...

Using IT Governance

Science.gov (United States)

Brobst, Jan; Council, Chip

2005-01-01

The discussion in this article is intended to provide an examination of why top management, IT management, and internal auditors should be interested in IT governance. Some aspects of IT management will be described including implementation, auditing, availability, security, and alignment. One governance framework, COBIT, will be utilized as a…

Regulation, Governance and Adaptation. Governance transformations in the Dutch and French liberalizing electricity industries

Energy Technology Data Exchange (ETDEWEB)

Niesten, E.M.M.I.

2009-06-11

For more than a decade, the European governments have focused their energy policies on creating one European competitive electricity market. Several regulations are introduced into the European electricity industries for this purpose: the energy firms have to unbundle the electricity networks from electricity generation and retail, and the consumers should be able to choose their electricity retailer. This thesis analyses which new governance structures emerged in the Dutch and French electricity industries as a result of these regulations for four types of electricity transactions: the network connection, network access, balancing and switching transactions. The parties in these electricity industries did not adopt a market, but hybrid forms of governance that remained extensively regulated. The efficiency of these new governance structures cannot be explained with the attributes of the transactions, as is proposed by transaction cost economics. This thesis therefore introduces the concept of adaptation into transaction cost economics. Adaptation is the adjustment by economic actors from one governance structure to another, and is characterized by three attributes: the identity of the future contracting party, the laterality of the adaption, and the type of response in the adaptation process. These attributes explain the governance transformations and the new governance structures in the two industries. Regulation continues to play a pervasive role in the liberalized electricity industries. It influences the attributes of the transactions, the new governance structures and the adaptation process.

Regulation, Governance and Adaptation. Governance transformations in the Dutch and French liberalizing electricity industries

International Nuclear Information System (INIS)

Niesten, E.M.M.I.

2009-01-01

For more than a decade, the European governments have focused their energy policies on creating one European competitive electricity market. Several regulations are introduced into the European electricity industries for this purpose: the energy firms have to unbundle the electricity networks from electricity generation and retail, and the consumers should be able to choose their electricity retailer. This thesis analyses which new governance structures emerged in the Dutch and French electricity industries as a result of these regulations for four types of electricity transactions: the network connection, network access, balancing and switching transactions. The parties in these electricity industries did not adopt a market, but hybrid forms of governance that remained extensively regulated. The efficiency of these new governance structures cannot be explained with the attributes of the transactions, as is proposed by transaction cost economics. This thesis therefore introduces the concept of adaptation into transaction cost economics. Adaptation is the adjustment by economic actors from one governance structure to another, and is characterized by three attributes: the identity of the future contracting party, the laterality of the adaption, and the type of response in the adaptation process. These attributes explain the governance transformations and the new governance structures in the two industries. Regulation continues to play a pervasive role in the liberalized electricity industries. It influences the attributes of the transactions, the new governance structures and the adaptation process.

Governance and Media Attention: A Research Agenda About How Media Affect (Network) Governance Processes

NARCIS (Netherlands)

Klijn, Erik Hans; Korthagen, Iris

2017-01-01

This article looks at the influence of media attention on governance processes and explores some new thoughts to incorporate in our theory building on governance. It systematically discusses recent theories about mediatization and connects them to what we know about governance in the field of Public

Governance of Governance in Higher Education: Practices and Lessons Drawn from the Portuguese Case

Science.gov (United States)

Magalhaes, Antonio; Veiga, Amelia; Amaral, Alberto; Sousa, Sofia; Ribeiro, Filipa

2013-01-01

The implementation of the governance reform of Portuguese higher education has been developed under the influence of "new public management" resulting in the loss of collegial governance. Additionally, the need for meta-governance of the higher education system and institutions to monitor institutional performance against policy…

Legitimacy and the Cost of Government

DEFF Research Database (Denmark)

Berggren, Niclas; Bjørnskov, Christian; Lipka, David

2015-01-01

While previous research documents a negative relationship between government size and economic growth, suggesting an economic cost of big government, a given government size generally affects growth differently in different countries. As a possible explanation of this differential effect, we......, in which two different measures of the size of government are interacted with government legitimacy, reveals that perceived legitimacy exacerbates a negative growth effect of government size in the long run. This could be interpreted as governments taking advantage of being regarded as legitimate in order...... to secure short-term support at a long-term cost to the economy....

Corporate Governance in Crisis? The Politics of EU Corporate Governance Regulation

DEFF Research Database (Denmark)

Horn, Laura

2012-01-01

on the transformation of company law and corporate governance in the last decade. Here, the article illustrates how company law has become increasingly focused on the rights of shareholders, while worker rights have been relegated to the area of social policies and labour law. The study also traces the shift from...... a legislative programme centred on company law harmonisation towards a regulatory approach based on minimum requirements and mutual recognition, increasingly geared at adjusting the governance of corporations to the demands of liberalised capital markets. The second section then reflects on the current...... developments in corporate governance regulation in the context of financial and economic crisis....

Performance Government: Activating and Regulating the Self-Governing Capacities of Teachers and School Leaders

Science.gov (United States)

O'Brien, Peter C.

2015-01-01

This article analyses "performance government" as an emergent form of rule in advanced liberal democracies. It discloses how teachers and school leaders in Australia are being governed by the practices of performance government which centre on the recently established Australian Institute for Teaching and School Leadership (AITSL) and…

Measuring interoperability maturity in government networks.

OpenAIRE

Huijsman, K.L.L.G.; Plomp, M.G.A.; Batenburg, R.S.

2012-01-01

The purpose of this paper is to create a model that describes the development of interorganisational collaboration in government networks that apply eGovernment. Contrary to several models that describe eGovernment from a government-to-citizen perspective, and primarily emphasise on the front office of eGovernment services, this paper focuses on the collaboration that takes place in the back office to enable successful eGovernment services. A maturity model was developed to describe and asses...

Theoretical interpretation of e-government implementation challenges in South Africa: A case study of a selected provincial government

Directory of Open Access Journals (Sweden)

Michael Twum-Darko

2015-04-01

Full Text Available This paper discusses factors influencing e-Government initiatives by African Governments to improve services to their citizens, businesses and their constituent. It further discusses, as a socially constructed phenomenon, the degree of readiness of governments to implement e-Government initiatives to improve services. The discussion uses Actor Network Theory (ANT and in particular the concepts of moments of translation and irreversibility as a lens through which to understand and interpret the social phenomenon. Although a number of e-Government researchers have argued that strong leadership and clear vision is required to implement e-Government initiatives, the view is that Governments have continuously failed to achieve the intended results. E-Government potentials and benefits which are well documented in Information Systems and e-Government research literature have not been realised by governments due to limited capabilities in the administration of the public service. The study applied a deductive approach where semi-structured interviews were used for data collection in a selected Provincial Government in South Africa. The outcome is a general framework to determine the readiness of South Africa government and generally, African governments for e-Government initiatives to achieve the intended results.

Dissecting signaling and functions of adhesion G protein-coupled receptors

DEFF Research Database (Denmark)

Araç, Demet; Aust, Gabriela; Calebiro, Davide

2012-01-01

G protein-coupled receptors (GPCRs) comprise an expanded superfamily of receptors in the human genome. Adhesion class G protein-coupled receptors (adhesion-GPCRs) form the second largest class of GPCRs. Despite the abundance, size, molecular structure, and functions in facilitating cell and matrix...... contacts in a variety of organ systems, adhesion-GPCRs are by far the most poorly understood GPCR class. Adhesion-GPCRs possess a unique molecular structure, with extended N-termini containing various adhesion domains. In addition, many adhesion-GPCRs are autoproteolytically cleaved into an N......-terminal fragment (NTF, NT, α-subunit) and C-terminal fragment (CTF, CT, β-subunit) at a conserved GPCR autoproteolysis-inducing (GAIN) domain that contains a GPCR proteolysis site (GPS). These two features distinguish adhesion-GPCRs from other GPCR classes. Though active research on adhesion-GPCRs in diverse areas...

Decentralization and Governance in Indonesia

NARCIS (Netherlands)

Holzhacker, Ronald; Wittek, Rafael; Woltjer, Johan

2016-01-01

I. Theoretical Reflections on Decentralization and Governance for Sustainable Society 1. Decentralization and Governance for Sustainable Society in Indonesia Ronald Holzhacker, Rafael Wittek and Johan Woltjer 2. Good Governance Contested: Exploring Human Rights and Sustainability as Normative Goals

Mobilizing Government

DEFF Research Database (Denmark)

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

2016-01-01

The nature of inter-organizational collaboration between government and other stakeholders is rapidly changing with the introduction of open social media (OSM) platforms. Characterized by a high degree of informality as well as a blurred personal/professional nature, OSM can potentially introduce...... changes and tensions in the well-established routines of the public sector. This paper aims at shedding light on such changes, presenting findings from a study on the use of an OSM platform, WeChat, in an interorganizational collaboration project between government, university, and industry stakeholders...

Corporate Governance Quality in Selected Transition Countries

Directory of Open Access Journals (Sweden)

Danila Djokic

2017-12-01

Full Text Available Important questions that concern the notion of good corporate governance focus on what good corporate governance is, who benefits from good corporate governance, and how corporate governance quality can be measured. The aim of our study was to broaden our understanding of the role of standards and codes of good corporate governance in improving governance practices.We found that not only formal regulations, standards, and governance codes, but also corporate governance indices-which make the assessment of companies’ governance practices possible-are important in measuring and improving governance quality. The results of the research based on the SEECGAN Index methodology indicated that mandatory requirements and voluntary recommendations of high governance standards had a positive impact on the corporate governance practice in Slovenia.

Global health justice and governance.

Science.gov (United States)

Ruger, Jennifer Prah

2012-01-01

While there is a growing body of work on moral issues and global governance in the fields of global justice and international relations, little work has connected principles of global health justice with those of global health governance for a theory of global health. Such a theory would enable analysis and evaluation of the current global health system and would ethically and empirically ground proposals for reforming it to more closely align with moral values. Global health governance has been framed as an issue of national security, human security, human rights, and global public goods. The global health governance literature is essentially untethered to a theorized framework to illuminate or evaluate governance. This article ties global health justice and ethics to principles for governing the global health realm, developing a theoretical framework for global and domestic institutions and actors.

Local Government System in Japan

Directory of Open Access Journals (Sweden)

Vladimir V. Redko

2016-12-01

Full Text Available The article is devoted to the issues of the activities of the local government of Japan. Particular attention is drawn to the legal framework and the material basis for the functioning of local self-government bodies. The system of local self-government is considered as a special form of self-government with a specific functional and meaning; system of municipal management and delegation of authority, as well as features of interaction between civil and imperious levels. The allocation of the city with a special status, as well as the financial structure of the local government of Japan, is considered in detail.

Trialogue model for ecosystem governance.

CSIR Research Space (South Africa)

Hattingh, J

2007-01-01

Full Text Available form and timescale to ensure good governance. In essence, good governance promotes democratic management of ecosystems and, by inference, prudentwater resourcemanagement. Consequently, it is likely that the type of governance that occurs most often... that, unless the imperative for civic science to support democratic governance is institutionalised through policy and strategy, it is unlikely that there will be sufficient human and financial investment in civic science as a means to promote...

Theoretical Framework for Corporate Governance

OpenAIRE

Georgescu Cristina Elena

2012-01-01

History has revealed that there is a never-ending evolution of theories or models of corporate governance. Companies are trying to instill the sense of governance into their corporate structure. This article is a review of literature on the range of theories in corporate governance. The fundamental theories in corporate governance began with the agency theory, expanded into stewardship theory and stakeholder theory and evolved to transaction cost theory. However, these theories address the ca...

Student Government and Student Participation in Junior College Governance--Models for the 1970's.

Science.gov (United States)

Deegan, William L.

It is the author's contention that student government revitalization will come only when student government begins to play a substantive role in policy making and implementation. The purpose of this paper is to consider, criticize, and propose a number of models for student participation in junior college governance. The first, a traditional…

Enacting Governance through Strategy

DEFF Research Database (Denmark)

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

2017-01-01

of strategy documents in city administration addresses these challenges. Our central claim is that strategy documents can be understood as a distinct discursive device through which local governments enact aspired governance configurations. We illustrate our argument empirically using two prominent examples...... that, while showing similar features and characteristics, are anchored in different administrative traditions and institutional frameworks: the city administrations of Sydney, Australia, and Vienna, Austria. The contribution of the paper is to show how strategy documents enact governance configurations...... along four core dimensions: the setting in space and time, the definition of the public, the framing of the res publica and legitimacy issues. Moreover, our comparative analysis of Sydney and Vienna gives evidence of differences in governance configurations enacted through strategy documents....

Energy Efficiency Governance: Handbook

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-07-01

This handbook has been written to assist EE practitioners, government officials and stakeholders to establish effective EE governance structures for their country. The handbook provides readers with relevant information in an accessible format that will help develop comprehensive and effective governance mechanisms. For each of the specific topics dealt with (see Figure 1 in the Handbook), the IEA offers guidelines for addressing issues, or directs readers to examples of how such issues have been dealt with by specific countries.

Codes of Good Governance

DEFF Research Database (Denmark)

Beck Jørgensen, Torben; Sørensen, Ditte-Lene

2013-01-01

Good governance is a broad concept used by many international organizations to spell out how states or countries should be governed. Definitions vary, but there is a clear core of common public values, such as transparency, accountability, effectiveness, and the rule of law. It is quite likely......, transparency, neutrality, impartiality, effectiveness, accountability, and legality. The normative context of public administration, as expressed in codes, seems to ignore the New Public Management and Reinventing Government reform movements....

Virtual Team Governance: Addressing the Governance Mechanisms and Virtual Team Performance

Science.gov (United States)

Zhan, Yihong; Bai, Yu; Liu, Ziheng

As technology has improved and collaborative software has been developed, virtual teams with geographically dispersed members spread across diverse physical locations have become increasingly prominent. Virtual team is supported by advancing communication technologies, which makes virtual teams able to largely transcend time and space. Virtual teams have changed the corporate landscape, which are more complex and dynamic than traditional teams since the members of virtual teams are spread on diverse geographical locations and their roles in the virtual team are different. Therefore, how to realize good governance of virtual team and arrive at good virtual team performance is becoming critical and challenging. Good virtual team governance is essential for a high-performance virtual team. This paper explores the performance and the governance mechanism of virtual team. It establishes a model to explain the relationship between the performance and the governance mechanisms in virtual teams. This paper is focusing on managing virtual teams. It aims to find the strategies to help business organizations to improve the performance of their virtual teams and arrive at the objectives of good virtual team management.

Model Penguatan Kapasitas Pemerintah Desa dalam Menjalankan Fungsi Pemerintahan Berbasis Electronic Government (E-Government menuju Pembangunan Desa Berdaya Saing

Directory of Open Access Journals (Sweden)

Sulismadi Sulismadi

2017-06-01

Full Text Available One aspect that needs to be studied more deeply about the village administration in the era of village autonomy is the ability of the human resources in the management of village government in accordance village governance objectives and the demands of, “Undang – undang no 06 Tahun 2014 about the village. The capacity of the village government deemed not qualified to run the authority possessed by law the village. Weak capacity of rural government impact on law implementation failure that led to the poor rural village development. This study examines these issues. This study used qualitative research methods. The unit of analysis of this research that the village government Landungsari Dau District of Malang, East Java. This study was conducted over three years (2016, 2017, 2018. The findings of the research during the last four months in the first year of the study is Landungsari village administration showed a good performance in governance at the village of village autonomy era (the era of the Village Law. The village government is able to carry out rural development planning, village administrative governance, and the financial management of the village properly. Nevertheless, the village government also faces serious problems is the lack of human resource capacity of the village administration, village very less quantity, and village officials do not understand the duties of each. To address these issues, the village government seeks to organize village governance based on information technology (e-government, but the effort has not worked well because the village government does not have a human resources professional in the field of information technology and the village government does not have enough budget to develop the e-government program. Therefore, the research team conducting FGD on the development of e-government program. FGD village government resulted in an agreement in cooperation with governmental science labs and e-government

Polycentrism in Global Health Governance Scholarship

Science.gov (United States)

Tosun, Jale

2018-01-01

Drawing on an in-depth analysis of eight global health networks, a recent essay in this journal argued that global health networks face four challenges to their effectiveness: problem definition, positioning, coalition-building, and governance. While sharing the argument of the essay concerned, in this commentary, we argue that these analytical concepts can be used to explicate a concept that has implicitly been used in global health governance scholarship for quite a few years. While already prominent in the discussion of climate change governance, for instance, global health governance scholarship could make progress by looking at global health governance as being polycentric. Concisely, polycentric forms of governance mix scales, mechanisms, and actors. Drawing on the essay, we propose a polycentric approach to the study of global health governance that incorporates coalitionbuilding tactics, internal governance and global political priority as explanatory factors. PMID:29325406

The European debate on governance networks

DEFF Research Database (Denmark)

Sørensen, Eva; Torfing, Jacob

2014-01-01

This paper aims to take stock of the European debate on governance networks in order to assess whether or not it has succeeded to develop a new a viable paradigm based on clear concepts, sound theories and methods and an expansive research agenda. The political and institutional conditions...... for the emergence of the Europe governance debate are analyzed and the notions of ‘governance’ and ‘governance networks’ are critically examined and defined. A brief assessment of the empirical significance of governance networks at different levels of governing is followed by a presentation and comparison...... development, the European debate on governance networks provides a new and important paradigm for understanding the emerging forms of multilateral action and pluricentric governance....

Practice Governance 101, v. 2013.

Science.gov (United States)

Hayes, David F

2013-03-01

Consensus governance is a principal weakness leading to group malfunction and failure. Inadequate group governance produces inadequate decisions, leading to inconsistent patient care, inadequate responses to marketplace challenges, and disregard for customers and strategic partners. The effectiveness of consensus management is limited by the pervasive incomplete knowledge and personal biases of partners. Additional structural weaknesses of group behavior include information cascade, the wisdom of the crowd, groupthink, pluralistic ignorance, analysis paralysis, peer pressure, and the herding instinct. Usual corporate governance is, by necessity, the governance model of choice. Full accountability of the decider(s) is the defining requirement of all successful governance models. Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Manajemen Perubahan, Tantangan Implementasi E-government

OpenAIRE

Prayitno, Edy

2008-01-01

Kegagalan implementasi e-government tidak lepas dari kesalahan manusia, para pelaku e-government, dalam menyikapi Perubahan sistem, dari sistem sebelumnya ke sistem e-government yang baru. Makalah ini mencoba menyampaikan hal-hal yang bisa dilakukan untuk mengantisipasi resistensi yang muncul akibat ketidaksiapan para pelaku e-government terhadap Perubahan sistem. Ini penting karena ketidaksiapan menerima Perubahan sistem seringkali menjadi penyebab ditolaknya implementasi e-government. Tidak...

The governance of hybrid organisations

DEFF Research Database (Denmark)

Spear, Roger; Cornforth, Chris

2010-01-01

The focus of this chapter is on the governance of third sector organizations (TSOs) and the challenges that are raised by hybridity. In particular it will focus on the question how does hybridity affect governance structures and processes and the challenges that governing bodies face?...

Human-centred Governance

DEFF Research Database (Denmark)

Bason, Christian

2017-01-01

Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

Partnerships and Governance

DEFF Research Database (Denmark)

Damgaard, Bodil

Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark.......Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark....

Managing e-government

DEFF Research Database (Denmark)

Rose, Jeremy; Persson, John Stouby; Heeager, Lise Tordrup

2015-01-01

Public sector managers take much of the responsibility for selecting, commissioning, implementing and realising benefits from information technology (IT) projects. However, e-Government initiatives often suffer from complexity, vision failure, lack of goal clarity and insufficient commitment....... These problems may stem from value traditions that are deeply ingrained in managers' cultural environments but not always in harmony with each other. A first step towards working with value complexity is to understand it; we synthesise a model of value positions for e-Government derived from major traditions...... in the public administration literature. Four value positions relevant to e-Government together with their IT assumptions are identified; they reflect the ideals of professionalism, efficiency, service and engagement. A qualitative investigation of Danish local authority managers displays both value congruence...

Government Services Information Infrastructure Management

Energy Technology Data Exchange (ETDEWEB)

Cavallini, J.S.; Aiken, R.J.

1995-04-01

The Government Services Information Infrastructure (GSII) is that portion of the NII used to link Government and its services, enables virtual agency concepts, protects privacy, and supports emergency preparedness needs. The GSII is comprised of the supporting telecommunications technologies, network and information services infrastructure and the applications that use these. The GSII is an enlightened attempt by the Clinton/Gore Administration to form a virtual government crossing agency boundaries to interoperate more closely with industry and with the public to greatly improve the delivery of government services. The GSII and other private sector efforts, will have a significant impact on the design, development, and deployment of the NII, even if only through the procurement of such services. The Federal Government must adopt new mechanisms and new paradigms for the management of the GSII, including improved acquisition and operation of GSII components in order to maximize benefits. Government requirements and applications will continue to evolv. The requirements from government services and users of form affinity groups that more accurately and effectively define these common requirements, that drive the adoption and use of industry standards, and that provide a significant technology marketplace.

Corporate Governance in Costa Rica

OpenAIRE

Gilberto E. Arce; Edgar Robles C.

2005-01-01

This paper examines corporate governance practices in Costa Rica. First, it estimates corporate governance charter measures using firm-level data for 87 Costa Rican firms and studies their impact on the firms` performance; here, the mean of the corporate governance charters for the publicly traded firms is equal to 56. 14. Second, new evidence is presented on de jure and de facto corporate governance charter measures at the firm level and on their effect on the performance of the firm. The re...

Shared governance in a clinic system.

Science.gov (United States)

Meyers, Michelle M; Costanzo, Cindy

2015-01-01

Shared governance in health care empowers nurses to share in the decision-making process, which results in decentralized management and collective accountability. Share governance practices have been present in hospitals since the late 1970s. However, shared governance in ambulatory care clinics has not been well established. The subjects of this quality project included staff and administrative nurses in a clinic system. The stakeholder committee chose what model of shared governance to implement and educated clinic staff. The Index of Professional Nursing Governance measured a shared governance score pre- and postimplementation of the Clinic Nursing Council. The Clinic Nursing Council met bimonthly for 3 months during this project to discuss issues and make decisions related to nursing staff. The Index of Professional Nursing Governance scores indicated traditional governance pre- and postimplementation of the Clinic Nursing Council, which is to be expected. The stakeholder committee was beneficial to the initial implementation process and facilitated staff nurse involvement. Shared governance is an evolutionary process that develops empowered nurses and nurse leaders.

Civil Society and Governance

DEFF Research Database (Denmark)

Hulgård, Lars

An illustration of how important the relationship is between civil society anbd governance. A short historic journey with four snapshots of times and situations that have provided interesting evidence about the connection between civil society and governance. My goal for the short historic journey...... is to make clear and hopefully even verify that providing knowledge about the impact of civil society and citizens’ participation on governance is one of the most urgent research tasks in the current period of time....

Transnational Governance and Constitutionalism

DEFF Research Database (Denmark)

Joerges, Christian; Sand, Inger-Johanne; Teubner, Gunther

of democratic governance. The book refers to this term as a yardstick to which then contributors feel committed even where they plead for a reconceptualisation of constitutionalism or a discussion of its functional equivalents. 'Transnational governance' is neither public nor private, nor purely international......The term transnational governance designates untraditional types of international and regional collaboration among both public and private actors. These legally-structured or less formal arrangements link economic, scientific and technological spheres with political and legal processes...

Governance, Trust, and Taxes

OpenAIRE

Schrøter Joensen, Juanna; Weihe, Guðrið

2013-01-01

This paper examines the role of social capital (trust) vis-à-vis the propensity of a country to be a tax haven. The empirical analysis corroborates that better governed countries have a higher ceteris paribus probability to be tax havens. However, social capital counteracts the effect of governance quality. This effect is so strong that the partial effect of governance quality is reversed for countries with the trust index in the top quartile – making these high trust countries le...

Canadian Government Electronic Information Policy.

Science.gov (United States)

Nilsen, Kirsti

1993-01-01

Examines development and evolution of Canadian government information policy in response to issues of preservation of data, information industry involvement in government data development and marketing, role of Crown copyright, and public access to government information in electronic formats. Six key information policy instruments are also…

E-government as Institutional Transformation

NARCIS (Netherlands)

Meijer, A.J.; Zouridis, S.

2004-01-01

Throughout the world, e-government has become a key element of modernization and government reform programs. E-government has put a spell on public administration from Singapore to Uruguay and from the United States to Hong Kong. This worldwide movement is interesting from the perspective of

Good governance as perceived by Dabawenyos

Directory of Open Access Journals (Sweden)

Adrian M. Tamayo

2016-12-01

Full Text Available The debate on good governance had shaped public policies of many governments. This study was conducted to obtain latent perspectives of good governance. A survey was conducted using two-stage cluster sampling in the first congressional district of Davao City involving 351 respondents. Findings reveal that the notion of good governance of Dabawenyos is primarily a government to implement the rule of law; peace and order is a necessity to facilitate market efficiency. Also, it was found that political leadership creates notions of good governance; public bestowed power to its political leaders as a matter of trust. On the other hand, leaders incorporate soft and hard forms of power in delegating powers without losing control, causing a widespread and significant impact on the formation and development of Davao’s perspectives of good governance. This is the rubber band effect of good governance leadership.

The Relationship of Government Revenue and Government Expenditure: A case study of Malaysia

OpenAIRE

Ullah, Nazim

2016-01-01

Malaysia is a developing Islamic state that faced budget deficit since 1998. But it is not accepted by all and hopes that state should be in a position of either balance budget or surplus budget. The optimum level of Government budget is the state where government expenditure is totally offset by source of government revenue and that can be achieved through increasing tax revenue or decreasing expenditure. The aim of this study to find out the theoretical relationship betwee...

Carbonizing forest governance: analyzing the consequences of REDD+ for multilevel forest governance

NARCIS (Netherlands)

Vijge, M.J.

2016-01-01

Carbonizing forest governance:

Analyzing the consequences of REDD+ for multilevel forest governance

Marjanneke J. Vijge

Despite the fifty years of global action to combat deforestation and forest degradation, the world is still

Visual Culture and Electronic Government: Exploring a New Generation of E-Government

Science.gov (United States)

Bekkers, Victor; Moody, Rebecca

E-government is becoming more picture-oriented. What meaning do stakeholders attach to visual events and visualization? Comparative case study research show the functional meaning primarily refers to registration, integration, transparency and communication. The political meaning refers to new ways of framing in order to secure specific interests and claims. To what the institutional meaning relates is ambiguous: either it improves the position of citizens, or it reinforces the existing bias presented by governments. Hence, we expect that the emergence of a visualized public space, through omnipresent penetration of (mobile) multimedia technologies, will influence government-citizen interactions.

The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation.

Science.gov (United States)

Gaffney, E A; Lee, S Seirin

2015-03-01

Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting for time delays associated with gene expression, reveals aberrant behaviours that are not consistent with early developmental self-organization, especially the requirement for exquisite temporal control. Attempts to reconcile the interpretation of Turing's ideas with an increasing understanding of the mechanisms driving zebrafish pigmentation suggests that one should reconsider Turing's model in terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106: , 8429-8434; Yamaguchi et al., 2007, PNAS, 104: , 4790-4793). Here the dynamics of pigment cells is subject to response delays implicit in the cell cycle and apoptosis. Hence we explore simulations of fish skin patterning, focussing on the dynamical influence of gene expression delays in morphogen-based Turing models and response delays for cell-based Turing models. We find that reconciling the mechanisms driving the behaviour of Turing systems with observations of fish skin patterning remains a fundamental challenge. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Weighted Components of i-Government Enterprise Architecture

Science.gov (United States)

Budiardjo, E. K.; Firmansyah, G.; Hasibuan, Z. A.

2017-01-01

Lack of government performance, among others due to the lack of coordination and communication among government agencies. Whilst, Enterprise Architecture (EA) in the government can be use as a strategic planning tool to improve productivity, efficiency, and effectivity. However, the existence components of Government Enterprise Architecture (GEA) do not show level of importance, that cause difficulty in implementing good e-government for good governance. This study is to explore the weight of GEA components using Principal Component Analysis (PCA) in order to discovered an inherent structure of e-government. The results show that IT governance component of GEA play a major role in the GEA. The rest of components that consist of e-government system, e-government regulation, e-government management, and application key operational, contributed more or less the same. Beside that GEA from other countries analyzes using comparative base on comon enterprise architecture component. These weighted components use to construct i-Government enterprise architecture. and show the relative importance of component in order to established priorities in developing e-government.

Measuring interoperability maturity in government networks.

NARCIS (Netherlands)

Huijsman, K.L.L.G.; Plomp, M.G.A.; Batenburg, R.S.

2012-01-01

The purpose of this paper is to create a model that describes the development of interorganisational collaboration in government networks that apply eGovernment. Contrary to several models that describe eGovernment from a government-to-citizen perspective, and primarily emphasise on the front office

E-Government: Initiatives, Developments, and Issues.

Science.gov (United States)

Aldrich, Duncan; Bertot, John Carlo; McClure, Charles R.

2002-01-01

Provides a background of government efforts to incorporate telecommunication and computer technologies to improve government performance and enhance citizen access to government information and services. Describes this symposium issue which discusses key issues that affect the success and implementation of electronic government initiatives. (LRW)

Measuring interoperability maturity in government networks

NARCIS (Netherlands)

Huijsman, K.L.L.G; Plomp, M.G.A.; Batenburg, R.S.

2012-01-01

The purpose of this paper is to create a model that describes the development of interorganisational collaboration in government networks that apply eGovernment. Contrary to several models that describe eGovernment from a government-to-citizen perspective, and primarily emphasise on the front office

Governing Governance : A formal framework for analysing institutional design and enactment governance

NARCIS (Netherlands)

King, T.C.

2016-01-01

This dissertation is motivated by the need, in today’s globalist world, for a precise way to enable governments, organisations and other regulatory bodies to evaluate the constraints they place on themselves and others. An organisation’s modus operandi is enacting and fulfilling contracts between

Oligomerization of G protein-coupled receptors: computational methods.

Science.gov (United States)

Selent, J; Kaczor, A A

2011-01-01

Recent research has unveiled the complexity of mechanisms involved in G protein-coupled receptor (GPCR) functioning in which receptor dimerization/oligomerization may play an important role. Although the first high-resolution X-ray structure for a likely functional chemokine receptor dimer has been deposited in the Protein Data Bank, the interactions and mechanisms of dimer formation are not yet fully understood. In this respect, computational methods play a key role for predicting accurate GPCR complexes. This review outlines computational approaches focusing on sequence- and structure-based methodologies as well as discusses their advantages and limitations. Sequence-based approaches that search for possible protein-protein interfaces in GPCR complexes have been applied with success in several studies, but did not yield always consistent results. Structure-based methodologies are a potent complement to sequence-based approaches. For instance, protein-protein docking is a valuable method especially when guided by experimental constraints. Some disadvantages like limited receptor flexibility and non-consideration of the membrane environment have to be taken into account. Molecular dynamics simulation can overcome these drawbacks giving a detailed description of conformational changes in a native-like membrane. Successful prediction of GPCR complexes using computational approaches combined with experimental efforts may help to understand the role of dimeric/oligomeric GPCR complexes for fine-tuning receptor signaling. Moreover, since such GPCR complexes have attracted interest as potential drug target for diverse diseases, unveiling molecular determinants of dimerization/oligomerization can provide important implications for drug discovery.

Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design

Science.gov (United States)

Basith, Shaherin; Cui, Minghua; Macalino, Stephani J. Y.; Park, Jongmi; Clavio, Nina A. B.; Kang, Soosung; Choi, Sun

2018-01-01

The primary goal of rational drug discovery is the identification of selective ligands which act on single or multiple drug targets to achieve the desired clinical outcome through the exploration of total chemical space. To identify such desired compounds, computational approaches are necessary in predicting their drug-like properties. G Protein-Coupled Receptors (GPCRs) represent one of the largest and most important integral membrane protein families. These receptors serve as increasingly attractive drug targets due to their relevance in the treatment of various diseases, such as inflammatory disorders, metabolic imbalances, cardiac disorders, cancer, monogenic disorders, etc. In the last decade, multitudes of three-dimensional (3D) structures were solved for diverse GPCRs, thus referring to this period as the “golden age for GPCR structural biology.” Moreover, accumulation of data about the chemical properties of GPCR ligands has garnered much interest toward the exploration of GPCR chemical space. Due to the steady increase in the structural, ligand, and functional data of GPCRs, several cheminformatics approaches have been implemented in its drug discovery pipeline. In this review, we mainly focus on the cheminformatics-based paradigms in GPCR drug discovery. We provide a comprehensive view on the ligand– and structure-based cheminformatics approaches which are best illustrated via GPCR case studies. Furthermore, an appropriate combination of ligand-based knowledge with structure-based ones, i.e., integrated approach, which is emerging as a promising strategy for cheminformatics-based GPCR drug design is also discussed. PMID:29593527

A new governance space for health

Science.gov (United States)

Kickbusch, Ilona; Szabo, Martina Marianna Cassar

2014-01-01

Global health refers to ‘those health issues which transcend national boundaries and governments and call for actions on the global forces and global flows that determine the health of people’. (Kickbusch 2006) Governance in this trans-national and cross-cutting arena can be analyzed along three political spaces: global health governance, global governance for health, and governance for global health. It is argued that the management of the interface between these three political spaces of governance in the global public health domain is becoming increasingly important in order to move the global health agenda forward. Global health governance refers mainly to those institutions and processes of governance which are related to an explicit health mandate, such as the World Health Organization; global governance for health refers mainly to those institutions and processes of global governance which have a direct and indirect health impact, such as the United Nations, World Trade Organization or the Human Rights Council; governance for global health refers to the institutions and mechanisms established at the national and regional level to contribute to global health governance and/or to governance for global health – such as national global health strategies or regional strategies for global health. It can also refer to club strategies, such as agreements by a group of countries such as the BRICS. In all three political spaces, the involvement of a multitude of state and non-state actors has become the norm – that is why issues of legitimacy, accountability and transparency have moved to the fore. The transnational nature of global health will require the engagement of all actors to produce global public goods for health (GPGH) and to ensure a rules-based and reliably financed global public health domain. PMID:24560259

A new governance space for health.

Science.gov (United States)

Kickbusch, Ilona; Szabo, Martina Marianna Cassar

2014-01-01

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

Governance and Development: Changing EU Policies

OpenAIRE

Hout, Wil

2010-01-01

textabstractAbstract This introductory article to the special issue on European Union, development policies and governance discusses how notions of ('good') governance have come to dominate development discourses and policies since the mid-1990s. The article argues that governance was part of the so-called Post-Washington Consensus, which understands governance reform as part of the creation of market societies. Although academics have commonly emphasised the fact that governance concerns the...

A Corporate Governance Index : Convergence and Diversity of National Corporate Governance Regulations

NARCIS (Netherlands)

Martynova, M.; Renneboog, L.D.R.

2010-01-01

The issue of appropriate corporate governance framework has been a focal point of recent reforms in many countries. This study provides a comprehensive comparative analysis of corporate governance regulatory systems and their evolution over the last 15 years in 30 European countries and the US. It

Lean government : Critical success factors for XBRL-based business-to-government reporting

NARCIS (Netherlands)

Bharosa, N.; De Winne, C.P.I.; Van Wijk, R.; Janssen, M.F.W.H.A.

2012-01-01

Lean government is all about doing better with less through the use of ICT and the realisation of process improvements. The recently introduced eXtensible Business Reporting Language (XBRL) has shown some initial success in realising lean government. Once data is stored in XBRL format, businesses

isk governance: Experience of Islamic banks

Directory of Open Access Journals (Sweden)

Siti Rohaya Mat Rahim

2015-05-01

Full Text Available Risk governance has evolved tremendously in the banking industry. Risk governance recommends the imperative roles of Chief Risk Officer (CRO to oversee risk. This study explores risk governance influence over the Islamic banks performances. Multivariate analysis techniques measure simultaneously via Structural Equation Modelling (SEM. This study employed cross-sectional sample of 200 Islamic banks across 21 countries for the year 2014. To examine risk governance and Islamic banks performance, the study captures seventeen variables developed from risk management and corporate governance (ROA, ROE, Profit Margin, CRO, Shariah committee member, CEO, board size, remuneration meeting, credit rating, external audit, accounting standard, loan loss provision, capital adequacy ratio, total deposit ratio, GDP, central bank lending rate and inflation. The simulation result reveals, risk governance act as mediating variables towards Islamic banks performance. This study has practical and significance contribution for Islamic banks to understand risk governance, aligning with the fundamental risk management and corporate governance

Uruguay - Corporate Governance Country Assessment

OpenAIRE

World Bank

2005-01-01

This report provides an assessment of Uruguay's corporate governance policy framework, enforcement and compliance practices. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Uruguay. The report identifies several key next steps that focus on implementa...

Local forms of governance in Denmark

DEFF Research Database (Denmark)

Torfing, Jacob

2010-01-01

of representative democracy. The supplement is taking its revenge as the interactive policy arenas are expanding and the role of elected politicians is being transformed from sovereign rulers to meta-governors. This development poses important challenges to the demand for effective and democratic governing......The proliferation of local forms of governance problematizes the well-established and highly normative idea that power and democracy in Denmark are organized in terms of a 'parliamentary chain of government', according to which the sovereign people elect the parliament, which in turn controls...... the government that governs the public administration through bureaucratic control. Consecutive waves of devolution have decentralized the Danish welfare state, and the power of local governments is now being challenged by the emergence of new forms of local governance that involve a plethora of private...

STATE-OWNED RURAL BANK PERFORMANCE: DO GOVERNMENT OWNERSHIP AND CORPORATE GOVERNANCE UNIQUENESS MATTER?

Directory of Open Access Journals (Sweden)

Azilsyah Noerdin

2016-12-01

Full Text Available It has been widely recognized that ownership structure has an impact on firm performance. This paper examines whether rural banks owned by government have poorer performance than those owned by private parties with the emphasis on corporate governance uniqueness of state-owned rural banks. 42 rural banks in Indonesia has been selected as the sample. MANOVA test is used to investigate the difference performance between the two types of the rural banks. The results show that state-owned rural banks perform poorer than their privately-owned counterparts. It is indicated by lower ROA ratio and higher OEOI and NPL ratios. The important implication of this finding suggets that government ownership impede boards of rural banks to implement good corporate governance practices in order to improve their banks performance.

Patching security governance : an empirical view of emergent governance mechanisms for cybersecurity

NARCIS (Netherlands)

van Eeten, M.J.G.

2017-01-01

Purpose: The issue of cybersecurity has been cast as the focal point of a fight between two conflicting governance models: the nation-state model of national security and the global governance model of multi-stakeholder collaboration, as seen in forums like IGF, IETF, ICANN, etc. There is a

Governance of the future

DEFF Research Database (Denmark)

Galløe, Lotte Rannveig

a different future for both parents and children. Thus, the approach to PMTO as a technology of the future indicates its expected prevalence in the future and its attempt to reach in to the future becoming of the child. The technology’s involvement of the relatives and its orientation towards shaping......In my presentation I will explore the concept, ‘technology of the future’, in public governance. Public governance within social services aims at changing the existing conditions for the marginalized citizens including children with special needs. I pose the question: what happens if public...... governance seek to chance the possible future conditions and targets the marginalized child’s relatives? Parent Management Training (PMTO) is studied as a technology of the future that expands and transforms governance. PMTO targets parents with aggressive and asocial children and aims to “create the parent...

42 CFR 494.180 - Condition: Governance.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Governance. 494.180 Section 494.180... Administration § 494.180 Condition: Governance. The ESRD facility is under the control of an identifiable governing body, or designated person(s) with full legal authority and responsibility for the governance and...

Governance and Trust in Higher Education

Science.gov (United States)

Vidovich, Lesley; Currie, Jan

2011-01-01

The adoption of more corporate models of governance is a contemporary trend in higher education. In the early 2000s, the Australian Government legislated national governance protocols for universities, using the policy lever of financial sanctions. These more corporate-style governance protocols followed similar changes in the UK, consistent with…

Nordic Corporate Governance Revisited

DEFF Research Database (Denmark)

Thomsen, Steen

2016-01-01

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

Roadmapping Future E-Government Research

Science.gov (United States)

Bicking, Melanie

Global electronic markets, virtual organisations, virtual identities, virtual products and services, and Internet-related crime are growing in prominence and importance. In a world that is increasingly non-physical and borderless, what are government's roles, responsibilities and limitations? The Internet plays a central role within the transformation process from traditional governments towards modern and innovative government that the requirements of an Information Society. Based on the findings of the eGovRTD2020 project, that aims at identifying key research challenges and at implementing a model for a holistic government with horizon 2020, this paper explains the necessity to investigate and understand the Internet and in particular government's role and responsibilities in it. Furthermore, the paper provides a research roadmap that details how to address certain issue related research questions.

42 CFR 460.62 - Governing body.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Governing body. 460.62 Section 460.62 Public Health... Administrative Requirements § 460.62 Governing body. (a) Governing body. A PACE organization must be operating under the control of an identifiable governing body (for example, a board of directors) or a designated...

22 CFR 221.43 - Governing law.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 221.43 Section 221.43 Foreign... Administration § 221.43 Governing law. This Guarantee shall be governed by and construed in accordance with the laws of the United States of America governing contracts and commercial transactions of the United...

Governance and performance: the performance of Dutch hospitals explained by governance characteristics.

Science.gov (United States)

Blank, Jos L T; van Hulst, Bart Laurents

2011-10-01

This paper describes the efficiency of Dutch hospitals using the Data Envelopment Analysis (DEA) method with bootstrapping. In particular, the analysis focuses on accounting for cost inefficiency measures on the part of hospital corporate governance. We use bootstrap techniques, as introduced by Simar and Wilson (J. Econom. 136(1):31-64, 2007), in order to obtain more efficient estimates of the effects of governance on the efficiency. The results show that part of the cost efficiency can be explained with governance. In particular we find that a higher remuneration of the board as well as a higher remuneration of the supervisory board does not implicate better performance.

Challenges facing transactional e-government systems

OpenAIRE

AI-Sebie, Madi M

2005-01-01

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University, 17/10/2005. A review of normative literature, in the field of e-government, indicates that the transactional stage of e-government is one of the most important to the implementation of an e-government system as it represents the highest level of interaction within organisations and between customers and government organisations. Due to the importance of the transactional stage of the e-govern...

Regulation of G protein-coupled receptor signalling: focus on the cardiovascular system and regulator of G protein signalling proteins

NARCIS (Netherlands)

Hendriks-Balk, Mariëlle C.; Peters, Stephan L. M.; Michel, Martin C.; Alewijnse, Astrid E.

2008-01-01

G protein-coupled receptors (GPCRs) are involved in many biological processes. Therefore, GPCR function is tightly controlled both at receptor level and at the level of signalling components. Well-known mechanisms by which GPCR function can be regulated comprise desensitization/resensitization

Tree agency and urban forest governance

DEFF Research Database (Denmark)

Konijnendijk, Cecil Cornelis

2016-01-01

governance also involving businesses and civic society. However, governance theory usually does not consider the role of non-human agency, which can be considered problematic due to, for example, the important role of urban trees in place making. The purpose of this paper is to provide further insight...... into the importance of considering tree agency in governance. Design/methodology/approach – Taking an environmental governance and actor network theory perspective, the paper presents a critical view of current urban forest governance, extending the perspective to include not only a wide range of human actors......, but also trees as important non-human actors. Findings – Urban forest governance has become more complex and involves a greater range of actors and actor networks. However, the agency of trees in urban forest governance is seldom well developed. Trees, in close association with local residents, create...

Government or Non-Government Schools: A British Colonial Legacy and Its Aftermath.

Science.gov (United States)

Whitehead, Clive

This paper discusses voluntary schools in the former British colonies of Singapore, Malaysia, and Fiji, and the relevance of some aspects of voluntaryism for government schooling in Australia. The first section presents the historical background to the voluntary principle by which schools are owned and operated by non-government agencies assisted…

Computerized and Networked Government Information Column

Science.gov (United States)

Stratford, Juri

2004-01-01

The efforts of the U.S. federal government to develop E-Government services have been the subject of many recent news stories. In February 2002, Arthur Andersen's Office of Government Services released a usability analysis of federal government Web sites. In addition, in February, Vice-President Cheney announced the release of a report detailing…

Characterizing Government Social Media Research

DEFF Research Database (Denmark)

Medaglia, Rony; Zheng, Lei

2016-01-01

As research on government social media continues to grow in quantity and scope, this area calls for mapping and systematization, in order to stimulate better-informed studies in the future. This paper draws on a comprehensive review of government social media literature in the e...... a four-point research agenda for future government social media research....

Government, Money, and International Politics

OpenAIRE

Hoppe, Hans-Hermann

2003-01-01

In this paper, the author deals with: (1) Definition of government; incentive structure under government: taxation, war and territorial expansion. (2) Origin of money; government and money; the devolution of money from commodity to fiat money. (3) International politics and monetary regimes; monetary imperialism and the drive toward a one-world central bank and fiat currency.

Governing the moral economy: Animal engineering, ethics and the liberal government of science

Science.gov (United States)

Harvey, Alison; Salter, Brian

2012-01-01

The preferred Western model for science governance has come to involve attending to the perspectives of the public. In practice, however, this model has been criticised for failing to promote democracy along participatory lines. We argue that contemporary approaches to science policy making demonstrate less the failure of democracy and more the success of liberal modes of government in adapting to meet new governance challenges. Using a case study of recent UK policy debates on scientific work mixing human and animal biological material, we show first how a ‘moral economy’ is brought into being as a regulatory domain and second how this domain is governed to align cultural with scientific values. We suggest that it is through these practices that the state assures its aspirations for enhancing individual and collective prosperity through technological advance are met. PMID:22507952

The N-terminal region of the dopamine D2 receptor, a rhodopsin-like GPCR, regulates correct integration into the plasma membrane and endocytic routes

Science.gov (United States)

Cho, DI; Min, C; Jung, KS; Cheong, SY; Zheng, M; Cheong, SJ; Oak, MH; Cheong, JH; Lee, BK; Kim, KM

2012-01-01

BACKGROUND AND PURPOSE Functional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D2 and D3 receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH The N-terminal region of the D2 receptor was gradually shortened or switched with that of the D3 receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY RESULTS Shortening the N-terminal region of the D2 receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D2 and D3 receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D2 receptors. CONCLUSIONS AND IMPLICATIONS Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D2 receptors. The N-terminal region of the D2 receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties. PMID:22117524

Benefit from the Government

NARCIS (Netherlands)

Evert Pommer; Jedid-Jah Jonker

2003-01-01

Original title: Profijt van de overheid. Income levels are determined to a considerable extent by the government, which exerts an influence through social security and taxation. The traditional purchasing power tables are a reflection of this. However, the influence of the government goes

The governance of adaptation

NARCIS (Netherlands)

Huitema, Dave; Adger, William Neil; Berkhout, Frans; Massey, Eric; Mazmanian, Daniel; Munaretto, Stefania; Plummer, Ryan; Termeer, Katrien

2016-01-01

The governance of climate adaptation involves the collective efforts of multiple societal actors to address problems, or to reap the benefits, associated with impacts of climate change. Governing involves the creation of institutions, rules and organizations, and the selection of normative

Convergence of Corporate and Public Governance

Directory of Open Access Journals (Sweden)

Gérard Hirigoyen

2013-06-01

Full Text Available By analyzing the differences between the corporate and public governance, theoretical and empirical research seems to indicate that the two domains of governance are far too different to share any common aspect. However, in this particular research, it has been argued that public governance is an application of corporate governance. Thus, the research question entails the description and analysis of this possible convergence of the two. Extensive research from literature on corporate governance has been undertaken to establish a relationship between the boards process and the roles that acts as a framework to bridge the gap separating corporate governance from public governance. Corporate governance, at a global level, exists in the for-profit as well as nonprofit organizations. Thus, the definition of this concept needs to be viewed from “an innovative” eye, considering the relationship between the process of the board and roles as characteristic of the public organization and private ones. As the private as well as public organizations are an application of corporate governance, the difference between the two gets narrowed. For the purpose of this research, the case of the French hospitals’ board has been taken into consideration. The members of the public board have been considered for the board process to perform their roles.

Spatial transcriptomics: paving the way for tissue-level systems biology.

Science.gov (United States)

Moor, Andreas E; Itzkovitz, Shalev

2017-08-01

The tissues in our bodies are complex systems composed of diverse cell types that often interact in highly structured repeating anatomical units. External gradients of morphogens, directional blood flow, as well as the secretion and absorption of materials by cells generate distinct microenvironments at different tissue coordinates. Such spatial heterogeneity enables optimized function through division of labor among cells. Unraveling the design principles that govern this spatial division of labor requires techniques to quantify the entire transcriptomes of cells while accounting for their spatial coordinates. In this review we describe how recent advances in spatial transcriptomics open the way for tissue-level systems biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Before e-Governance and e-Government, Back to Basics! The Case of the Caribbean

Directory of Open Access Journals (Sweden)

Pearson A. Broome

2015-09-01

Full Text Available This conceptual article discusses the opportunities and challenges presented by e-government and e-governance in the Caribbean. An understanding of the issues inherent in these phenomena is crucially important, particularly for the governance systems of small island developing states in the Caribbean. In practice, however, they are rarely discussed,—not least because their complexity is often misunderstood or inappropriately unacknowledged as new directions by political scientists and policy planners. Moreover, the foundational debate on information and communication technologies (ICTs and their impact on governance and the wider implications for development remain muted owing to the theatrical commotion in other “pressing” aspects of Caribbean political life. As a consequence, this article contextualizes the debate by bringing to the fore a discussion on the importance of understanding the broader political, social, and economic issues and the implications of the use of ICTs and development. In the analysis, a balance is struck to avoid the often disproportionate technocratic parables of a future technological cornucopia being peddled by some international development agencies and officials in the region. Such a macro discussion is necessary if as development advocates and citizens, we are to realize any gains while acknowledging the limitations an enabling e-government and e-governance environment could portend.

Examining Auditing as an Essential Element of Financial Management and Good Governance in Local Government

Directory of Open Access Journals (Sweden)

Sindisile Maclean

2014-06-01

Full Text Available The purpose of the article is to address issues of auditing in the context of financial management as a contribution to good governance. Generally, not all local governments have effective and operational audit units and committees. As a result, auditing is not used as an essential element of good governance and this leads to bad audit outcomes like disclaimers and adverse opinions. The bad audit outcomes in local government have motivated the researcher to conduct the study on auditing. There are internal factors within the municipalities as well as external factors that are of interest and directed the researcher to have desire and commitment to make a contribution in this particular field of research. The key issues, amongst others, are principles of financial management, financial strategy, auditing functions such as forensic auditing, fraud auditing, forensic accounting and detection of fraud, including accounting systems and auditor’s role. This article will also attempt to reinforce existing theories and add value to local government financial discourse and good governance.

Local governments' participation in intergovernmental e-government projects: a comparative network analysis of two case study's

OpenAIRE

Vander Elst, Simon; De Rynck, Filip

2012-01-01

Both the Belgian federal and Flemish regional government have framed the development of a series of authentic information sources as a key solution to reduce administrative burden for companies and citizens as these crossroads banks allow the sharing of information between different government agencies at different levels of government. The ultimate goal is to realize a more integrated, efficient and effective government service delivery towards citizens and companies. In our paper, we will c...

An atlas of Caenorhabditis elegans chemoreceptor expression.

Directory of Open Access Journals (Sweden)

Berta Vidal

2018-01-01

Full Text Available One goal of modern day neuroscience is the establishment of molecular maps that assign unique features to individual neuron types. Such maps provide important starting points for neuron classification, for functional analysis, and for developmental studies aimed at defining the molecular mechanisms of neuron identity acquisition and neuron identity diversification. In this resource paper, we describe a nervous system-wide map of the potential expression sites of 244 members of the largest gene family in the C. elegans genome, rhodopsin-like (class A G-protein-coupled receptor (GPCR chemoreceptors, using classic gfp reporter gene technology. We cover representatives of all sequence families of chemoreceptor GPCRs, some of which were previously entirely uncharacterized. Most reporters are expressed in a very restricted number of cells, often just in single cells. We assign GPCR reporter expression to all but two of the 37 sensory neuron classes of the sex-shared, core nervous system. Some sensory neurons express a very small number of receptors, while others, particularly nociceptive neurons, coexpress several dozen GPCR reporter genes. GPCR reporters are also expressed in a wide range of inter- and motorneurons, as well as non-neuronal cells, suggesting that GPCRs may constitute receptors not just for environmental signals, but also for internal cues. We observe only one notable, frequent association of coexpression patterns, namely in one nociceptive amphid (ASH and two nociceptive phasmid sensory neurons (PHA, PHB. We identified GPCRs with sexually dimorphic expression and several GPCR reporters that are expressed in a left/right asymmetric manner. We identified a substantial degree of GPCR expression plasticity; particularly in the context of the environmentally-induced dauer diapause stage when one third of all tested GPCRs alter the cellular specificity of their expression within and outside the nervous system. Intriguingly, in a number of

Light-dependent governance of cell shape dimensions in cyanobacteria

Directory of Open Access Journals (Sweden)

Beronda L Montgomery

2015-05-01

Full Text Available The regulation of cellular dimension is important for the function and survival of cells. Cellular dimensions, such as size and shape, are regulated throughout the life cycle of bacteria and can be adapted in response to environmental changes to fine-tune cellular fitness. Cell size and shape are generally coordinated with cell growth and division. Cytoskeletal regulation of cell shape and cell wall biosynthesis and/or deposition occurs in a range of organisms. Photosynthetic organisms, such as cyanobacteria, particularly exhibit light-dependent regulation of morphogenes and generation of reactive oxygen species and other signals that can impact cellular dimensions. Environmental signals initiate adjustments of cellular dimensions, which may be vitally important for optimizing resource acquisition and utilization or for coupling the cellular dimensions with the regulation of subcellular organization to maintain optimal metabolism. Although the involvement of cytoskeletal components in the regulation of cell shape is widely accepted, the signaling factors that regulate cytoskeletal and other distinct components involved in cell shape control, particularly in response to changes in external light cues, remain to be fully elucidated. In this review, factors impacting the inter-coordination of growth and division, the relationship between the regulation of cellular dimensions and central carbon metabolism, and consideration of the effects of specific environment signals, primarily light, on cell dimensions in cyanobacteria will be discussed. Current knowledge about the molecular bases of the light-dependent regulation of cellular dimensions and cell shape in cyanobacteria will be highlighted.

Tax administration good governance

NARCIS (Netherlands)

Végh, Gyöngyi; Gribnau, Hans

2018-01-01

There is no doubt that tax administration is a complex matter. It is institutionalised by a governance framework which is strongly influenced by legal traditions, state governance approaches, historical developments, and norms and values of society. While there are many common aspects of national

Student Participation in Governance

Science.gov (United States)

Deegan, William L.; And Others

1970-01-01

The success of student government activities on any campus is significantly affected by the amount of student participation permitted in the institution's decision-making processes. The traditional" model of government--characterized by tokenism--often results in the separate jurisdictions" model-- characterized by fragmentation and interest…

The Forgotten Promise of E-government Maturity

DEFF Research Database (Denmark)

Andersen, Kim Normann; Medaglia, Rony; Vatrapu, Ravi

2011-01-01

Assessing e-government responsiveness is one of the major gaps in the currently dominant e-government maturity models. While we have a relatively large pool of models focusing on technological and organizational integration from a supply side perspective, measures of responsiveness of e-government...... that one third of central government agencies did not respond at all, and close to 80% of the ministries provided none or incomplete answers. Local government responds faster and provides answers that are more complete and accurate than those provided by central government. Implications for e-government...

Corporate Governance Country Assessment : Uruguay

OpenAIRE

World Bank

2005-01-01

This report provides an assessment of Uruguay's corporate governance policy framework, enforcement and compliance practices. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Uruguay. The report identifies several key next steps that focus on implementation including: Improving corporate information, particularly ownership disclosure, related party transac...

Japan's nuclear PA activity in local governments

International Nuclear Information System (INIS)

Fujii, Nobuyuki

1995-01-01

This presentation emphasises some points of PA activities, based on the experience of 'cooperation projects for local governments'. Local governments distribute the public information directly to the residents. This is very important because officers of the local government can be the opinion leaders of the region. Local government exist very close to the residents, while the central government is a distant and faceless existence for the local people. It is believed that the local governments play an imperative role in PA activities. In other words, we must further utilize the organizations and functions of the local governments to implement PA activities. In conclusion, three recommendations are offered. Firstly, enough budget and authority should be given to the local governments as far as PA activities in their areas are concerned, and most of such activities should be entrusted to the local governments. Local governments should place more public relations officers, and continue the manpower development. Second, with regard to highly technical or specialized issues which a local governments cannot treat alone, related organizations like JAERO should support their PA activities. Third, such related organizations should also cooperate with local government including assistance in providing know-how, when their public information activities focus on educators, journalists, or the women. These three points should be given due consideration in our cooperation projects for the local governments, and JAERO is doing its best every day

Convergence of Corporate and Public Governance

OpenAIRE

Gérard Hirigoyen; Radhoine Laouer

2013-01-01

By analyzing the differences between the corporate and public governance, theoretical and empirical research seems to indicate that the two domains of governance are far too different to share any common aspect. However, in this particular research, it has been argued that public governance is an application of corporate governance. Thus, the research question entails the description and analysis of this possible conve...

Romanian government bond market

Directory of Open Access Journals (Sweden)

Cornelia POP

2012-12-01

Full Text Available The present paper aims to present the level of development reached by Romanian government bond market segment, as part of the country financial market. The analysis will be descriptive (the data series available for Romania are short, based on the secondary data offered by the official bodies involved in the process of issuing and trading the Romanian government bonds (Romanian Ministry of Public Finance, Romanian National Bank and Bucharest Stock Exchange, and also on secondary data provided by the Federation of European Stock Exchanges.To enhance the market credibility as a benchmark, a various combination of measures is necessary; among these measures are mentioned: the extension of the yield curve; the issuance calendars in order to improve transparency; increasing the disclosure of information on public debt issuance and statistics; holding regular meetings with dealers, institutional investors and rating agencies; introducing a system of primary dealers; establishing a repurchase (repo market in the government bond market. These measures will be discussed based on the evolution presented inside the paper.The paper conclude with the fact that, until now, the Romanian government bond market did not provide a benchmark for the domestic financial market and that further efforts are needed in order to increase the government bond market transparency and liquidity.

Coordination through IT governance: a literature review

OpenAIRE

L. Caporarello

2006-01-01

Organizations seek to mirror their corporate governance arrangements in the activities of their key subunits – as IT function – in order to lower their organizational coordination costs. Some researches evidence that the mode of corporate governance significantly influences the mode of IT governance: organizations that have centralized their corporate governance also tend to centralize their IT governance, whereas organizations that have decentralized their corporate governance tend to decent...

The essence of governance in health development

Directory of Open Access Journals (Sweden)

Kirigia Joses

2011-03-01

Full Text Available Abstract Background Governance and leadership in health development are critically important for the achievement of the health Millennium Development Goals (MDGs and other national health goals. Those two factors might explain why many countries in Africa are not on track to attain the health MDGs by 2015. This paper debates the meaning of 'governance in health development', reviews briefly existing governance frameworks, proposes a modified framework on health development governance (HDG, and develops a HDG index. Discussion We argue that unlike 'leadership in health development', 'governance in health development' is the sole prerogative of the Government through the Ministry of Health, which can choose to delegate (but not abrogate some of the governance tasks. The general governance domains of the UNDP and the World Bank are very pertinent but not sufficient for assessment of health development governance. The WHO six domains of governance do not include effective external partnerships for health, equity in health development, efficiency in resource allocation and use, ethical practises in health research and service provision, and macroeconomic and political stability. The framework for assessing health systems governance developed by Siddiqi et al also does not include macroeconomic and political stability as a separate principle. The Siddiqi et al framework does not propose a way of scoring the various governance domains to facilitate aggregation, inter-country comparisons and health development governance tracking over time. This paper argues for a broader health development governance framework because other sectors that assure human rights to education, employment, food, housing, political participation, and security combined have greater impact on health development than the health systems. It also suggests some amendments to Siddigi et al's framework to make it more relevant to the broader concept of 'governance in health development

The essence of governance in health development.

Science.gov (United States)

Kirigia, Joses Muthuri; Kirigia, Doris Gatwiri

2011-03-28

Governance and leadership in health development are critically important for the achievement of the health Millennium Development Goals (MDGs) and other national health goals. Those two factors might explain why many countries in Africa are not on track to attain the health MDGs by 2015. This paper debates the meaning of 'governance in health development', reviews briefly existing governance frameworks, proposes a modified framework on health development governance (HDG), and develops a HDG index. We argue that unlike 'leadership in health development', 'governance in health development' is the sole prerogative of the Government through the Ministry of Health, which can choose to delegate (but not abrogate) some of the governance tasks. The general governance domains of the UNDP and the World Bank are very pertinent but not sufficient for assessment of health development governance. The WHO six domains of governance do not include effective external partnerships for health, equity in health development, efficiency in resource allocation and use, ethical practises in health research and service provision, and macroeconomic and political stability. The framework for assessing health systems governance developed by Siddiqi et al also does not include macroeconomic and political stability as a separate principle. The Siddiqi et al framework does not propose a way of scoring the various governance domains to facilitate aggregation, inter-country comparisons and health development governance tracking over time.This paper argues for a broader health development governance framework because other sectors that assure human rights to education, employment, food, housing, political participation, and security combined have greater impact on health development than the health systems. It also suggests some amendments to Siddigi et al's framework to make it more relevant to the broader concept of 'governance in health development' and to the WHO African Region context. A strong

Data governance for health care providers.

Science.gov (United States)

Andronis, Katerina; Moysey, Kevin

2013-01-01

Data governance is characterised from broader definitions of governance. These characteristics are then mapped to a framework that provides a practical representation of the concepts. This representation is further developed with operating models and roles. Several information related scenarios covering both clinical and non-clinical domains are considered in information terms and then related back to the data governance framework. This assists the reader in understanding how data governance would help address the issues or achieve a better outcome. These elements together enable the reader to gain an understanding of the data governance framework and how it applies in practice. Finally, some practical advice is offered for establishing and operating data governance as well as approaches for justifying the investment.

m-government legal and regulatory framework

African Journals Online (AJOL)

Wondwossen Mulugeta

Legal Framework for Implementation of m-Government in Ethiopia: Best. Practices and Lessons ... opportunity to government and businesses to provide enhanced mobile .... provide effective governance, offer increased service delivery and ...

Integrating adaptive governance and participatory multicriteria methods: a framework for climate adaptation governance

NARCIS (Netherlands)

Munaretto, S.; Siciliano, G.; Turvani, M.

2014-01-01

Climate adaptation is a dynamic social and institutional process where the governance dimension is receiving growing attention. Adaptive governance is an approach that promises to reduce uncertainty by improving the knowledge base for decision making. As uncertainty is an inherent feature of climate

Governing the moral economy: animal engineering, ethics and the liberal government of science.

Science.gov (United States)

Harvey, Alison; Salter, Brian

2012-07-01

The preferred Western model for science governance has come to involve attending to the perspectives of the public. In practice, however, this model has been criticised for failing to promote democracy along participatory lines. We argue that contemporary approaches to science policy making demonstrate less the failure of democracy and more the success of liberal modes of government in adapting to meet new governance challenges. Using a case study of recent UK policy debates on scientific work mixing human and animal biological material, we show first how a 'moral economy' is brought into being as a regulatory domain and second how this domain is governed to align cultural with scientific values. We suggest that it is through these practices that the state assures its aspirations for enhancing individual and collective prosperity through technological advance are met. Copyright © 2012 Elsevier Ltd. All rights reserved.

Educational Governance in Denmark

Science.gov (United States)

Moos, Lejf

2014-01-01

Denmark has entered global competition by expanding collaboration with European countries, which is profoundly impacting the public sector and school governance. Relations between the state and institutions are transforming from traditional democratic, public-sector models of governance into new forms characterized as corporate and market-driven…

Learning Democratic Global Governance.

Science.gov (United States)

Haavelsrud, Magnus

1996-01-01

Outlines a model process of developing knowledge from within different groups and cultures to allow more equitable participation of all world societies in the definition of global governance. Reviews concepts relevant to education's contributions toward learning and creating democratic global governance. Discusses the educational utility of…

Calvin on church and government

Directory of Open Access Journals (Sweden)

W.A. Dreyer

2010-07-01

Full Text Available This article examines Calvin’s understanding of civil govern- ment as well as the relationship between church and govern- ment against the background of radical political change during the sixteenth century. It becomes clear that Calvin had an organic understanding of church, government and people. These three entities are interwoven and interact on the basis of the covenant and civil contract. Calvin’s approach, however, is not limited to the covenant, but has a surprising richness and diversity. He integrated theological, juristic and philosophical concepts in his understanding of the state. It is further shown that Calvin’s high regard for civil government, entrenched the corpus christianum, even though he clearly distinguished between ecclesiastical and civil governance. It is also shown that Calvin had a fundamental influence on many of the political concepts which are generally accepted within modern democra- cies.

Governance in Southeast Asia: Issues and Options

OpenAIRE

Gonzalez, Eduardo T.; Mendoza, Magdalena L.

2003-01-01

This paper attempts to analyze governance systems in Southeast Asia and proposes some policy suggestions that can improve governance practices in the region. It also discusses the links between governance and official development assistance and the role of the Japan Bank for International Cooperation. To put the discussion on governance systems in a proper context, the paper discusses the governance and growth nexus in Southeast Asia; describes the operating governance systems in Southeast As...

Remittances Deteriorate Governance

OpenAIRE

Faisal Z. Ahmed

2013-01-01

I use a natural experiment of oil-price-driven remittance flows to poor, non-oil-producing Muslim countries to demonstrate that remittances deteriorate the quality of governance, especially in countries with weak democratic institutions. The results indicate that a 1 standard deviation increase in remittances raises corruption by 1.5 index points (on a 6-point scale), which is equivalent to a [dollar]600 decrease in per capita GDP. Concomitantly, remittances may enable governments to reduce t...

ETHICS IN GOVERNMENT: ANTI-CORRUPTION MEASURES

OpenAIRE

Aktan, Coşkun Can

2018-01-01

Unethicalbehavior in government is viewed as a situation where there isfraudulent or dishonest conduct or improper behaviour by people who are in aposition or power. Bribery, extortion, embezzlement,the use of legislated powersby government officials for illegitimate private gain, nepotism, rent seeking etc.are some examples forunethical behavior in government.How to deal with unethical behavior in government?. How to curb corruption?Experience demo...

The Research Frontier in Corporate Governance

DEFF Research Database (Denmark)

Ahrens, Thomas; Filatotchev, Igor; Thomsen, Steen

2011-01-01

in our knowledge of corporate governance and is likely to lead of a rethink of central concepts like shareholder value, debt governance, and management incentives (2) what do we know and what do we need to how about the impact of national institutions on corporate governance? (3) What research questions......In this paper we attempt to identify the research frontier in corporate governance using three different approaches: (1) what challenges does the financial crisis 2007–2009 pose for corporate governance research? We show that the financial crisis is a huge natural experiment which has exposed gaps...

Government debt in Greece: An empirical analysis

Directory of Open Access Journals (Sweden)

Gisele Mah

2014-06-01

Full Text Available Greek government debt has been increasing above the percentage stated in the growth and stability path from 112.9% in 2008 to 175.6% in 2013. This paper investigates the determinants of the general government debt in Greek by means of Vector Error Correction Model framework, Variance Decomposition and Generalized Impulse Response Function Analysis. The analysis showed a significant negative relationship between general government debt and government deficit, general government debt and inflation. Shocks to general government and inflation will cause general government debt to increase. Government deficit should be increased since there is gross capital formation included in its calculation which could be invested in income generating projects. The current account balance should be reduced by improving the net trade balance.

Institutional change and corporate governance reform

Directory of Open Access Journals (Sweden)

Harilaos Mertzanis

2011-04-01

Full Text Available The global financial crisis has posed challenges to financial institutions governance. Meeting these challenges requires an understanding of governance dynamics in relation to institutions’ performance within a changing environment. The nature and scope of institutional response to a changing environment depends upon inherited governance structures, including socioeconomic conventions and rules of behavior at the macro level and time, expertise and common commitment of directors at the micro level. Innovation and learning-by-doing in governance can be an effective reform strategy. Innovation in governance may include the establishment of new norms of economic behavior and the transformation of decision-making process and the reallocation of responsibilities to directors and senior management. This may also inform regulatory approaches in strengthening financial institutions governance, based on improved disclosure, independent and competent boards

A molecular pharmacologist's guide to G protein-coupled receptor crystallography

NARCIS (Netherlands)

Piscitelli, Chayne L.; Kean, James; de Graaf, C.; Deupi, Xavier

2015-01-01

G protein-coupled receptor (GPCR) structural biology has progressed dramatically in the last decade. There are now over 120 GPCR crystal structures deposited in the Protein Data Bank of 32 different receptors from families scattered across the phylogenetic tree, including class B, C, and Frizzled

isk governance: Experience of Islamic banks

OpenAIRE

Siti Rohaya Mat Rahim; Fauziah Mahat

2015-01-01

Risk governance has evolved tremendously in the banking industry. Risk governance recommends the imperative roles of Chief Risk Officer (CRO) to oversee risk. This study explores risk governance influence over the Islamic banks performances. Multivariate analysis techniques measure simultaneously via Structural Equation Modelling (SEM). This study employed cross-sectional sample of 200 Islamic banks across 21 countries for the year 2014. To examine risk governance and Islamic banks performanc...

Thematic report on public governance

International Nuclear Information System (INIS)

Bouder, F.

2002-01-01

The objective of the FSC workshop was to learn from the process that led to the ratification by the Finnish Parliament, on 18 May 2001, of the Decision in Principle on the final disposal facility for spent nuclear fuel in Olkiluoto, Eurajoki. One of the objectives clearly expressed by the NEA was to help government to make the right decisions, including by looking at successful policy making and decision-making practices. This gave 'Public Governance' issues a prominent role in the debates. In addition, the meeting was conceived as a discussion between stakeholders, which, interestingly, also made it an exercise in 'Public Governance'. This purpose of this report is to identify some key governance lessons that emerged from looking at this process in detail. It looks at the difficult policy context in which the Decision in Principle had to be taken. It highlights the governance challenge that emerged and suggests some key findings that could possibly be relevant in other similar circumstances. (author)

Groundwater governance in Asia: present state and barriers to implementation of good governance

Science.gov (United States)

Tanaka, T.

2014-09-01

The present state of groundwater governance in Asia was reviewed. The main problem regarding groundwater resources in each Asian country is overexploitation, causing water level decline, land subsidence and salt water intrusion. For those groundwater hazards, many countries have established regulations such as laws and regulations as countermeasures. However, those laws and regulations are not the basic laws on groundwater resources, but only for countermeasures to prevent groundwater hazards. Common problems and barriers for implementing groundwater governance in Asian countries are that there is more than one institute with different and sometimes overlapping responsibilities in groundwater management. To overcome those conflicts among institutions and establishment of good governance, it is necessary to establish an agency in the government as one coordinate function reinforcing the direct coordination and facilitation of groundwater policy-making and management. As one such framework, the conceptual law called the Water Cycle Basic Law, which is under planning in Japan, is examined in this paper.

Negotiating Collaborative Governance Designs

DEFF Research Database (Denmark)

Plotnikof, Mie

2017-01-01

This chapter addresses the design and implementation issues of collaborative governance, a public management practice aimed at involving stakeholders in problem-solving and public innovation.......This chapter addresses the design and implementation issues of collaborative governance, a public management practice aimed at involving stakeholders in problem-solving and public innovation....

Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.

Directory of Open Access Journals (Sweden)

Arya J Bahrami

Full Text Available Liver fibrosis is mediated by hepatic stellate cells (HSCs, which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR-mediated signaling, via endothelin-1 (ET-1 and angiotensin II (AngII, increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5, an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs. Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury.

Why Governments Intervene

DEFF Research Database (Denmark)

Brown, Dana; Knudsen, Jette Steen

for this phenomenon. Research has tended either to rely on cross-country comparisons that generalize tendencies within given countries; or to over-generalize global trends. The current paper analyzes particular CSR policies in two countries – Denmark and the United Kingdom. We find that the rationales for government...... initiatives on CSR are neither consistent across countries or within them. Instead, CSR policies are utilized to address multiple issues crossing various areas of governance, including domestic social policy, global competitiveness policies and foreign policy....

Toward an E-Government Semantic Platform

Science.gov (United States)

Sbodio, Marco Luca; Moulin, Claude; Benamou, Norbert; Barthès, Jean-Paul

This chapter describes the major aspects of an e-government platform in which semantics underpins more traditional technologies in order to enable new capabilities and to overcome technical and cultural challenges. The design and development of such an e-government Semantic Platform has been conducted with the financial support of the European Commission through the Terregov research project: "Impact of e-government on Territorial Government Services" (Terregov 2008). The goal of this platform is to let local government and government agencies offer online access to their services in an interoperable way, and to allow them to participate in orchestrated processes involving services provided by multiple agencies. Implementing a business process through an electronic procedure is indeed a core goal in any networked organization. However, the field of e-government brings specific constraints to the operations allowed in procedures, especially concerning the flow of private citizens' data: because of legal reasons in most countries, such data are allowed to circulate only from agency to agency directly. In order to promote transparency and responsibility in e-government while respecting the specific constraints on data flows, Terregov supports the creation of centrally controlled orchestrated processes; while the cross agencies data flows are centrally managed, data flow directly across agencies.

Governance and human resources for health

Directory of Open Access Journals (Sweden)

Dieleman Marjolein

2011-11-01

Full Text Available Abstract Despite an increase in efforts to address shortage and performance of Human Resources for Health (HRH, HRH problems continue to hamper quality service delivery. We believe that the influence of governance is undervalued in addressing the HRH crisis, both globally and at country level. This thematic series has aimed to expand the evidence base on the role of governance in addressing the HRH crisis. The six articles comprising the series present a range of experiences. The articles report on governance in relation to developing a joint vision, building adherence and strengthening accountability, and on governance with respect to planning, implementation, and monitoring. Other governance issues warrant attention as well, such as corruption and transparency in decision-making in HRH policies and strategies. Acknowledging and dealing with governance should be part and parcel of HRH planning and implementation. To date, few experiences have been shared on improving governance for HRH policy making and implementation, and many questions remain unanswered. There is an urgent need to document experiences and for mutual learning.

Governance and human resources for health.

Science.gov (United States)

Dieleman, Marjolein; Hilhorst, Thea

2011-11-24

Despite an increase in efforts to address shortage and performance of Human Resources for Health (HRH), HRH problems continue to hamper quality service delivery. We believe that the influence of governance is undervalued in addressing the HRH crisis, both globally and at country level. This thematic series has aimed to expand the evidence base on the role of governance in addressing the HRH crisis. The six articles comprising the series present a range of experiences. The articles report on governance in relation to developing a joint vision, building adherence and strengthening accountability, and on governance with respect to planning, implementation, and monitoring. Other governance issues warrant attention as well, such as corruption and transparency in decision-making in HRH policies and strategies. Acknowledging and dealing with governance should be part and parcel of HRH planning and implementation. To date, few experiences have been shared on improving governance for HRH policy making and implementation, and many questions remain unanswered. There is an urgent need to document experiences and for mutual learning.

Corporate governance and intellectual capital

Directory of Open Access Journals (Sweden)

Rahmat Alizadeh

2014-01-01

Full Text Available The purpose of this paper is to examine the association between corporate governance and Intellectual capital in the pharmaceutical companies accepted in Tehran Stock Exchange over the period 2004-2009 using a regression based model. The study investigates the impacts of three some independent variables of the corporate governance (i.e. the number of board members, the relative extent of nonexecutive to executive directors, the auditing committee. The results suggest that corporate governance had no special effect on intellectual capital in the pharmaceutical companies. Furthermore among corporate governance's variables, the first one (i.e. board size had negative impact on firms' intellectual capital and the second and the third variables had no effects on intellectual capital.

Good Governance in the EU

Directory of Open Access Journals (Sweden)

Gina Livioara GOGA

2009-10-01

Full Text Available Considering the EU adhesion, good governance has been analyzed from different perspectives, in the judicial literature being an analytic model or a normative concept. Some authors have wondered if this concept is a fashion, comprising some older ideas and principles, while other authors have asserted that the reasons why different methods of governance appear in the EU are based on “the complexity and the uncertainty of the problems on the agenda, an irreducible, the new approaches on public administration and law, hidden competencies, legitimacy and subsidiarity”. At a normative level, the White Paper of European Governance consecrated five principles on which good governance is based upon: openness, participation, responsibility, efficiency and coherence.

ETHICS in GOVERNMENT: ANTI-CORRUPTION MEASURES

Directory of Open Access Journals (Sweden)

Coskun Can Aktan

2015-07-01

Full Text Available Unethicalbehavior in government is viewed as a situation where there isfraudulent or dishonest conduct or improper behaviour by people who are in aposition or power. Bribery, extortion, embezzlement,the use of legislated powersby government officials for illegitimate private gain, nepotism, rent seeking etc.are some examples forunethical behavior in government.How to deal with unethical behavior in government?. How to curb corruption?Experience demonstrates that establishing an ethical government is not an easytask. There is no single approach to curb (political corruption effectively. Instead,controlling (political corruption requires a wide range of strategies.Thisdescriptive survey aims to explore the anti-corruptions measures in general.

GOVERNANCE ON THE INTERNET. MEASURING THE PERFORMANCES OF E-GOVERNANCE IN BUCHAREST MUNICIPALITIES

Directory of Open Access Journals (Sweden)

ANDREI ELVADEANU

2011-04-01

Full Text Available This paper analyzes the electronic governance and how it’s functioning in Romania. Being part of a larger institutional reform process, the electronic governance represents a new approach of the relation between Government and the citizen, with the purpose of increasing the participative dimension of the politic action, and as a way to provide more efficient services by the public agencies. E-governance uses information technologies (especially the Internet in the public sector, in order to improve the activity of bureaucratic institutions and encourage citizen participation. This paper analyzes the concept of electronic governance and with a focus on the obvious differences between the ideal model and the way in which these policies are actually implemented in Romania. The analysis was made for the 6 town-halls in Bucharest, but can offer a good sample of how egovernance is made in Romania. The instrument used for measurements is the comprehensive Rutgers egovernance performance index, covered in detail in the article. The areas taken into consideration were the public services offered by the institutions, the usage degree by the citizens and the civic participation dimension, understood as a bi-directional communication between the institutions and the citizen. The final part of the paper is dedicated to explaining the results, with recommendations for the Romanian public institutions. The research has its limits, but the results can draw attention over an institutional process that can represent a huge positive change in the way that governance is usually understood to be made in Romania and a very important improvement in the relation between state and society.

Global Governance, Educational Change

Science.gov (United States)

Mundy, Karen

2007-01-01

In the last half decade, a rising literature has focused on the idea that processes of economic, political and social globalization require analysis in terms of governance at the global level. It is argued in this article that emerging forms of global governance have produced significant challenges to conventional conceptions of international…

Open government objectives and participation motivations

NARCIS (Netherlands)

Wijnhoven, Alphonsus B.J.M.; Ehrenhard, Michel Léon; Kuhn, Johannes

2015-01-01

Open government aims, among others, at improving engagement of citizens in public sector activities. To realize this potential, we need to understand citizens' motivations to engage in the many different variants of open government. This article identifies motivations for open government

Transformative governance of urban social-ecological systems

Science.gov (United States)

A central aspect of adaptive governance is a learning process that can help communities achieve environmental objectives. Adaptive governance is a framework for managing social-ecological systems, and is the precursor to transformative governance. Adaptive governance accounts for...

Do Policy Networks lead to Network Governing?

DEFF Research Database (Denmark)

Damgaard, Bodil

This paper challenges the notion that creation of local policy networks necessarily leads to network governing. Through actor-centred case studies in the area of municipally implemented employment policy in Denmark it was found that the local governing mode is determined mainly by the municipality......’s approach to local co-governing as well as by the capacity and interest of key private actors. It is argued that national legislation requesting the creation of local policy networks was not enough to assure network governing and the case studies show that local policy networks may subsist also under...... hierarchical governing modes. Reasons why hierarchical governing modes prevail over network governing in some settings are identified pointing to both actor borne and structural factors. Output indicators of the four cases do not show that a particular governing mode is more efficient in its employment policy...

Corporate governance of the environment.

OpenAIRE

Purvis, B.

2005-01-01

The global pursuit of a more sustainable future cannot be achieved without the active engagement of the business community. The challenge for business has been to strategically engage with and embed environmental responsibility within their wider corporate governance to create effective corporate governance of the environment. The assumption would appear to be, that we have already witnessed the construction of such governance, delivered through the attainment of a paradigmatic shift in corpo...

THE SOUND OF CORPORATE GOVERNANCE

Directory of Open Access Journals (Sweden)

DUMITRASCU LUMINITA MIHAELA

2012-07-01

Full Text Available The paper explores the corporate governance and corporate social responsibility in music industry, by reviewing the literature and investigating the aspects in the context of a sample made by top companies in this domain. The paper spotlighting the mutual connections between corporate governance and corporate social responsibility. The research methodology used consists in investigate the corporate governance codes. It’s about a qualitative interpretive research methodology that was adopted. The findings suggest the intercorelation of corporate governance with corporate social responsibility. The main contribution of the author consists in the fact that the added value of this paper and the original contribution leads in the intercorelation of these two aspects of corporate governance and corporate social responsibility, the findings beeing interesting, implying that recent preoccupation with corporate governance in music industry is starting to be equable by some attention to social responsibility aspects, with growing appreciation of their interdependencies. Previous literature has researched corporate governance and corporate social responsibility independently. Due to this fact, this paper is considering them jointly. The paper is important for both practical and theoretical aspects: for managers and also can serve as the basis for future research on this topic. The current paper is realized in the doctoral program entitled “PhD in Economics at the Standards of European Knowledge- DoEsEc”, scientific coordinator Prof. PhD Niculae Feleaga, Institution: The Academy of Economic Studies Bucharest, Faculty of Accounting and Management Informatic System, Department of International Accounting, period of research 2009-2012.

Russian Initiatives in Internet Governance

Directory of Open Access Journals (Sweden)

Sergey Sergeevich Shirin

2014-01-01

Full Text Available The article is devoted to the research of Russian initiatives concerning its participation in international system of Internet governance. In the research, conceptual and theoretic basis for participation of state governments in Internet governance is given, academic discourse of this issue is assessed, the review of main Russian initiatives made from 2005 (since the second stage of the World Summit on Information Society till the present day is carried out. The conclusion is made that the most successful Internet governance initiative of Russia is the implementation of cyrillic top level domains. Much less successful are Russian attempts to reconstruct existing organizational structure of Internet governance. Russian policy is assessed as a policy of preferring loud statements and PR rather than real influence on development of Internet technologies. Russia consideres Internet as political resource and tries to increase its influence on decision making process on a political, not operational level of Internet governance. The author states that federal government of the United States of America has fully lost the control on the domain name systems. These functions are going to be given to the private sector, while ICANN, which was established according to the Memorandum of Understanding/Joint Project Agreement with U.S. Department of Commerce, is becoming a truly independent international organization. Considering this, the author comes to the conclusion that political transformations for the sake of Russia are already made. He also forecast that next initiatives of Russia will be directed to the segmentation of the Internet.

Corporate Governance in Publicly Traded Canadian Companies

OpenAIRE

Hu, Jie; Wang, Chong

2011-01-01

We investigate the effectiveness of corporate governance practices in this paper, focusing on the corporate governance practices implemented by TSX listed companies in Canada. We analyze the determinants of the effectiveness of corporate governance practices and test whether corporate governance mechanisms relate to quality of accounting earnings and company performance. We obtain mixed results from regression analyses indicating that corporate governance mechanisms are not significantly rela...

Governance and Sustainable Peace in Nigeria

African Journals Online (AJOL)

DrNneka

been amassing the Nation's wealth neglecting the masses. ... and Movement for the Actualization of the Sovereign State of Biafra .... Having examined good governance, what does bad governance entail? .... governance with utmost sense of sincerity, transparency and accountability. But .... Mismanagement of Public Fund.

RELEVANCE OF CORPORATE GOVERNANCE IN NIGERIAN ...

African Journals Online (AJOL)

economy, their corporate governance is of prime interest to government, ... supervisory framework and unethical practices among top banking chiefs ... Corporate Governance of Public Companies in Nigeria (2003) which sees corporate ... are more interested in their banks' profitability, soundness and good health while the.

Paradoxes around good governance

NARCIS (Netherlands)

A.G. Dijkstra (Geske)

2013-01-01

textabstract Good governance is not a new concept Ambrogio Lorenzetti made his frescoes on good and bad governance already in the years 1338-1340 They can be viewed in the Palazzo Publicco on one of the most beautiful squares of the world, the Piazza del Campo in Siena, Italy I assume many of you

The Economy Governing During Globalization Era

Directory of Open Access Journals (Sweden)

Ion Bucur

2006-09-01

Full Text Available World and national economie governing is an essential premise of the political stability and democratic evolution. In this study are approached theoretical and practical aspects of the economie governing. Theoretical acquisitions in this field highlit multiple perspectives of approaching and difficulties to characterize this complex and multisized fenomenon. A possible theory of governing the economy needs to use some concepts and mechanisms particular to more scientific fields (political science, economy, cibernetics, the theory of systems and others. The dinamic character and the instability of the present system of governing imposed the analysis of the factors and conditions which have generated the crises of the national and world economic governing. In this context, there are indentified the forms of manifesting the instability (lack of legitimacy, transpa¬rence and democratic responsability, and also the direction of necessary action to implement an efficient and responsable economic governing.

The Economy Governing During Globalization Era

Directory of Open Access Journals (Sweden)

Ion Bucur

2006-07-01

Full Text Available World and national economie governing is an essential premise of the political stability and democratic evolution. In this study are approached theoretical and practical aspects of the economie governing. Theoretical acquisitions in this field highlit multiple perspectives of approaching and difficulties to characterize this complex and multisized fenomenon. A possible theory of governing the economy needs to use some concepts and mechanisms particular to more scientific fields (political science, economy, cibernetics, the theory of systems and others. The dinamic character and the instability of the present system of governing imposed the analysis of the factors and conditions which have generated the crises of the national and world economic governing. In this context, there are indentified the forms of manifesting the instability (lack of legitimacy, transpa¬rence and democratic responsability, and also the direction of necessary action to implement an efficient and responsable economic governing.

CORPORATE GOVERNANCE IN INDIA: AN ANALYSIS

Directory of Open Access Journals (Sweden)

Meghna Thapar

2017-03-01

Full Text Available Corporate governance is a process, relation and mechanism set up for the corporations and firms based on certain guidelines and principles by which a company is controlled and directed. The principles provided in the system ensure that the company is governed in a way that it is able to set and achieve its goals and objectives in the context of the social, regulatory and market environment, and is able to maximize profits and also benefit those whose interest is involved in it, in the long run. The division and distribution of rights and responsibilities among different participants in the corporation (such as the board of directors, managers, shareholders, creditors, auditors, regulators, and other stakeholders and inclusion of the rules and procedures for making decisions in corporate affairs are identified with the help of Corporate Governance mechanism and guidelines. The need to make corporate governance in India transparent was felt after the high profile corporate governance failure scams like the stock market scam, the UTI scam, Ketan Parikh scam, Satyam scam, which were severely criticized by the shareholders. Thus, Corporate Governance is not just company administration but more than that and includes monitoring the actions, policies, practices, and decisions of corporations, their agents, and affected stakeholders thereby ensuring fair, efficient and transparent functioning of the corporate management system. By this paper, the authors intend to examine the concept of corporate governance in India with regard to the provisions of corporate governance under the Companies Act 2013. The paper will highlight the importance and need of corporate governance in India. We will also discuss the important case laws which contributed immensely in the emergence of corporate governance in India.

GOMoDo: A GPCRs online modeling and docking webserver.

Directory of Open Access Journals (Sweden)

Massimo Sandal

Full Text Available G-protein coupled receptors (GPCRs are a superfamily of cell signaling membrane proteins that include >750 members in the human genome alone. They are the largest family of drug targets. The vast diversity and relevance of GPCRs contrasts with the paucity of structures available: only 21 unique GPCR structures have been experimentally determined as of the beginning of 2013. User-friendly modeling and small molecule docking tools are thus in great demand. While both GPCR structural predictions and docking servers exist separately, with GOMoDo (GPCR Online Modeling and Docking, we provide a web server to seamlessly model GPCR structures and dock ligands to the models in a single consistent pipeline. GOMoDo can automatically perform template choice, homology modeling and either blind or information-driven docking by combining together proven, state of the art bioinformatic tools. The web server gives the user the possibility of guiding the whole procedure. The GOMoDo server is freely accessible at http://molsim.sci.univr.it/gomodo.

Regulation of G Protein-Coupled Receptors by Ubiquitination

Directory of Open Access Journals (Sweden)

Kamila Skieterska

2017-04-01

Full Text Available G protein-coupled receptors (GPCRs comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

Citizen-Centric Governance Indicators: Measuring and Monitoring Governance by Listening to the People and Not the Interest Groups

OpenAIRE

Ivanyna, Maksym; Shah, Anwar

2009-01-01

Governance indicators are now widely used as tools for conducting development dialogue, allocating external assistance, and influencing foreign direct investment. This paper argues that available governance indicators are not suitable for these purposes as they do not conceptualize governance and fail to capture how citizens perceive the governance environment and outcomes in their countri...

2010 E-Government Act Report

Data.gov (United States)

Department of Veterans Affairs — This report describes VA’s accomplishments inimplementing the requirements of the E-Government Act of 2002, Section 202(g)and the Open Government Directive dated...

'Joined Up' Local Governments?

DEFF Research Database (Denmark)

Bjørnå, Hilde; Casale, Donatella; Hajnal, Gyorgy

eforms inspired by NPM have raised many challenges to governments, such as time lags between implementation and (any) results, fragmentation due to unbundling monolithic organizations and mediocre support from public sector stakeholders (Christensen/Lægreid 2007, Dunleavy et al. 2006, Hood...... measures (6 2004). JUG involves an emphasis on coordinating governmental activities, for example through partnerships and horizontal governing approaches, to eliminate contradictions between different policies, and to deliver integrated and seamless services from a citizen’s perspective (Lægreid et al......, for example one-stop-shops, often combined with e-government solutions (Norway, Italy, Hungary and Germany), public sector recentralisation and de-agencification (Ireland) or refined strategies for steering the ‘landscape of corporatized organizations‘ (Hungary and Austria)....

Electoral Governance in Brazil

Directory of Open Access Journals (Sweden)

Vitor Marchetti

2012-06-01

Full Text Available Electoral governance has increasingly more frequently been the object of study of the comparative politics literature. This article examines the electoral governance institutional model adopted in Brazil and its consequences for political/electoral competition. It is argued herein that Brazil’s Electoral Justice System, motivated by the institutional design, has ended up becoming one of the main actors of the country’s recent democratic consolidation, being decisive not only with regard to rule adjudication and application, but also to rulemaking. With the purpose of assessing this governance model in action, three important recent rulings by Brazil’s Electoral Justice System are analysed here: verticalization of the coalitions, reduction in the number of councillors, and party loyalty.

People, Governance and Forests—The Stumbling Blocks in Forest Governance Reform in Latin America

Directory of Open Access Journals (Sweden)

Arnoldo Contreras-Hermosilla

2011-01-01

Full Text Available This article examines common barriers to achieving adequate levels of forest resource governance in countries of Latin America. It looks at the deficiencies of the policy and regulatory frameworks affecting forests, the common failure to impose the rule of law, the main factors that constrain the effectiveness of government actions in the forest sector and at the political barriers to introducing reforms for change in governance structures. The elimination of these barriers acquires new importance in the implementation of successful REDD+ programs in the countries of the region.

Corporate governance cycles during transition

DEFF Research Database (Denmark)

Mygind, Niels; Demina, Natalia; Gregoric, Aleksandra

2004-01-01

-ing or exit stage. During transition the cycle reflects: privatization often with a high proportion of employee ownership like in Russia and in Slovenia; strong pressures for restructuring and owner-ship changes; limited possibility for external finance because of embryonic development of the fi......-nancial system. To provide simple hypothesis tests, we use Russian enterprise data for 1995-2003 and Slovenian data covering 1998-2003. In spite of differences in institutional development, con-cerning privatization and development of corporate governance institutions, we find that govern-ance cycles are broadly...... of ownership on managers, external domestic and foreign owners. JEL-codes: G3, J5, P2, P3 - Keywords: corporate governance, life-cycle, privatization, ownership change, transition economies, Russia and Slovenia....

Local government and climate policy

International Nuclear Information System (INIS)

Burger, H.; Menkveld, M.; Coenen, F.H.J.M.

2000-01-01

Local government in the Netherlands could play a greater role than they currently do in reducing greenhouse gas emissions in the country. This fact formed the motivation for initiating the research project on Local Government and Climate Policy. Many local climate options are known in theory. Options for reduction that lie within the sphere of influence of Dutch local government are, for example, sustainable building or encouraging the utilisation of sustainable energy. But actual practice turns out to be rather refractory. If such options are to be implemented, then one has to overcome institutional barriers, such as the co-operation between different departments in the same local authority. The objective of this research is to improve the contribution that local government makes to climate policy

Developing a Generic Framework for E-Government

OpenAIRE

Gerald Grant; Derek Chau

2005-01-01

Electronic government (e-government) initiatives are pervasive and form a significant part of government investment portfolio in almost all countries around the world. However, understanding of what is meant by e-government is still nascent and becomes complicated because the construct means different things to different people. Consequently, the conceptualization and implementation of e-government programs are diverse and are often difficult to assess and compare across different contexts of...

Marine informational governance, a conceptual framework

NARCIS (Netherlands)

Hoefnagel, E.W.J.; Vos, de B.I.; Buisman, F.C.

2013-01-01

Marine governance involves interaction between networks and actors from different types and levels of organizations. The concept of multi-level or network governance steps away from the assumptions that supra-national and national government at the macro level is the dominant policy making unit. At

Governance and Development: Changing EU Policies

NARCIS (Netherlands)

W. Hout (Wil)

2010-01-01

textabstractAbstract This introductory article to the special issue on European Union, development policies and governance discusses how notions of ('good') governance have come to dominate development discourses and policies since the mid-1990s. The article argues that governance was part of the

The Value of Open Government Data

DEFF Research Database (Denmark)

Jetzek, Thorhildur; Avital, Michel; Bjørn-Andersen, Niels

Government data has been accumulated for centuries in protected repositories and registries as public record and a matter of civil order. Recently, the Open Government Data (OGD) movement has emerged as a group that focuses on facilitating open access to government data. Proponents of OGD...

Structure modeling of all identified G protein-coupled receptors in the human genome.

Science.gov (United States)

Zhang, Yang; Devries, Mark E; Skolnick, Jeffrey

2006-02-01

G protein-coupled receptors (GPCRs), encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER) method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(alpha) root-mean-squared deviation from native of 4.6 angstroms, with a root-mean-squared deviation in the transmembrane helix region of 2.1 angstroms. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness and robustness

Structure modeling of all identified G protein-coupled receptors in the human genome.

Directory of Open Access Journals (Sweden)

Yang Zhang

2006-02-01

Full Text Available G protein-coupled receptors (GPCRs, encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(alpha root-mean-squared deviation from native of 4.6 angstroms, with a root-mean-squared deviation in the transmembrane helix region of 2.1 angstroms. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness

Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

Science.gov (United States)

Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

2015-10-01

Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious

Interorganizational Care needs Horizontal Governance

OpenAIRE

Spierenburg, Monique; van de Schoot, Rian

2016-01-01

Interorganizational Governance isn’t a theme for research yet. Because of the complexity of problems of (new) clients there is an urgent need to cooperate in networks of welfare, care, initiatives of citizens, general practitioners and others. And because of the policy of the (local) government, the transition of the healthcare systems, with the vision to help people close by. In these practice we see new ideas and forms of governance.What’s the problem? Decentralization, integration and pers...

Corporate Governance Disclosure in Malaysia

OpenAIRE

ONG, Wei Jiin

2006-01-01

This research provides evidence on corporate governance disclosure in Malaysia based on a sample of 25 Malaysian public listed companies on the Kuala Lumpur Composite Index (KLCI) in the year 1998 and 2005 that are listed on the Bursa Malaysia. The purpose of this dissertation is to examine whether after the launch of the Malaysian Code on Corporate Governance (HLFC, 2000) following the 1997/98 financial crisis, corporate governance in Malaysia has improved in terms of disclosure information ...

Quality of Governance and Local Development: The Case of Top Nine Performing Local Government Units in the Philippines

Directory of Open Access Journals (Sweden)

MA. NIÑA I. ADRIANO

2014-08-01

Full Text Available There is a large body of literature that studies the link between good governance and development in a country level. However, only a few have exploited the same study in the local government unit (LGU setting. This study attempts to establish the relationship between the quality of governance and the state of local development of the Top 9 Performing LGUs in the Philippines (La Union, Albay, Cavite, Ilocos Norte, Makati City Valenzuela City, Taguig City, Davao City and Angeles City as measured by the Local Governance Performance Management System (LGPMS, the nationwide governance performance evaluation and management tool used in the Philippines. I used the data generated by the LGPMS, particularly the state of local governance and the state of local development, to see if there is a relationship between the two variables using Spearman’s correlation coefficient. Results revealed that that there is no relationship between the quality of governance and the state of local development in the consistently top performing LGUs in the Philippines for the period 2009-2011. The findings of this study will be useful to government officials such as public administrators, LGU executives, policy makers, researchers, and students of public administration in addressing the issue of good governance and local development in their respective LGUs.

Local government and utility firms’ debts

Directory of Open Access Journals (Sweden)

Marko Primorac

2011-12-01

Full Text Available The global financial crisis has affected the Croatian local public sector. In such circumstances, local government units’ debts and borrowing should be approached with caution. The highly interwoven financial operations of local government units and their utilities indicate the need for analysis of consolidated financial statements of local governments and utility companies in order to gain an insight into the real financial “health” of local units. Accordingly, the main aim of this paper is to analyze the size and the structure of the consolidated (local government and utility companies local public debt in Croatia. Accordingly, the paper presents the financial position of local government units supplemented with information on the financial operations of utility companies, with particular emphasis on the size and structure of their liabilities and gross and net debt. Although the current Budget Law does not require formal preparation of consolidated financial statements by local governments and their utility firms, consolidation is stipulated by International Public Sector Accounting Standards (IPSAS. The application of IPSAS regulations would be helpful in determining overall direct and indirect exposure of local government units arising from the financial operations of their utilities.

31 CFR 596.310 - Terrorism List Government.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Terrorism List Government. 596.310... OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS REGULATIONS General Definitions § 596.310 Terrorism List Government. The term Terrorism List Government...

Nordic Corporate Governance and Industrial Foundations

DEFF Research Database (Denmark)

Thomsen, Steen

to the international audience. This paper therefore reviews the Nordic corporate governance model with special emphasis on a unique ownership structure, industrial foundations (foundations that own business companies). Rather than a meticulous description of details it emphasizes the Nordic model as a mode......The Nordic countries have attracted considerable attention in recent years as a benchmark for good governance. However, while the political governance characteristics of the Nordic model – particularly the welfare state - are well understood, its corporate governance characteristics remain elusive...

Open Government: A Tool for Democracy?

Directory of Open Access Journals (Sweden)

Emiliana De Blasio

2016-12-01

Full Text Available The growing disconnection between citizens and decision-makers is pushing politics towards a re-shaping of institutional design. New spaces of political participation are sustained and even reinforced by communication, especially by digital communication. Governments and public administrations can find and use different models to facilitate citizens’ participation; e-government, open government and a specific design of digital democracy. In this respect, open government can constitute a way to re-connect citizens and political institutions, but at the same time, it can also be an “appealing” tool to institutionalize bottom-up participation and so anesthetizing it. The aim of this article is to present the first findings of an international research project about open government and participatory platforms in four European countries (France, Italy, Spain, the UK. The study tries to understand if participatory platforms can improve the quality of democracy, and if open government can contribute to democratizing democracy.

Maritime governance speed, flow, form process

CERN Document Server

Roe, Michael

2016-01-01

This book provides an original analysis of the problems facing global governance and in particular that of one of the most globalised of all industries – shipping. Central to all global trade and its dramatic growth, shipping faces difficulties of governance stemming from its every globalised nature. The current characteristics of global governance – nation-state fixation, anachronistic institutions, inadequate stakeholder involvement and an over-domination of owner interests are dwarfed by the problems of stasis and fixation which means that policies to address problems of safety, the environment and security are inadequate. This book provides a full and wide ranging discussion of how governance can be animated in a global context so that the dynamism of the maritime industry and its problems can be prevented, regulated and understood. Its unique approach to governance makes it essential reading for all maritime policy-makers and those analysing maritime issues, alongside those with an interest in govern...

Making Migrants Governable

DEFF Research Database (Denmark)

Stenum, Helle

2012-01-01

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

Political Will and Strategic Use of YouTube to Advancing Government Transparency: An Analysis of Jakarta Government-Generated YouTube Videos

OpenAIRE

Chatfield , Akemi ,; Brajawidagda , Uuf

2013-01-01

Part 2: Open Government Data and Transparency; International audience; Government transparency is critical to cut government bureaucracy and corruption, which diminish political accountability and legitimacy, erode trust in government, and hinder citizen engagement and government performance. Previously, Jakarta’s local governments lacked government transparency, holding high-level meetings under a close-door policy, sustaining a critical and fundamental flaw in policy-making and fueling gove...

The information published by local governments. The websites of Catalonia’s municipal governments

Directory of Open Access Journals (Sweden)

M Corcoy Rius

2013-07-01

Full Text Available Introduction. The information issued by government institutions must be complete and intelligible so that citizens are able to exercise their right to participation based on informed decisions and the media professionals can use consider these institutions as reliable sources of information. This article presents the results of the development and application of a method to evaluate the information offered by the websites of the municipal governments of Catalonia in order to encourage policymakers to introduce improvements to these platforms. Methods. The sample of study includes the institutional websites run by the government of 947 municipalities of Catalonia. The evaluation is based on 41 purpose-created indicators. Results. The results have been represented on an online geographical mapping tool, titled Map of Good Practices in Local Public Communication, which offers individual and general results and statistics. Conclusions. The publication of results has quickly led to improvements in the sample of websites under analysis, which has led the research team to apply the same evaluation method to the websites of the municipal governments of other five Spanish autonomous communities.

A genome-wide inventory of neurohormone GPCRs in the red flour beetle Tribolium castaneum

DEFF Research Database (Denmark)

Hauser, Frank; Cazzamali, Giuseppe; Williamson, Michael

2008-01-01

in Tribolium was the occurrence of a vasopressin GPCR and a vasopressin peptide. So far, the vasopressin/GPCR couple has not been detected in any other insect with a sequenced genome (D. melanogaster and six other Drosophila species, Anopheles gambiae, Aedes aegypti, Bombyx mori, and A. mellifera). Tribolium...

INTERNATIONAL GOVERNMENT SECURITIES: SPECIFIC FUNCTIONING

Directory of Open Access Journals (Sweden)

N. Versal

2013-11-01

Full Text Available It’s disclosed the features of the international government securities market during 1993 – 2012: main players are the developed countries (Western Europe, Canada, USA with the increasing role of developing countries; debt crises have the negative impact as on the development of the international government securities market, but also on the international capital market as a whole; debt crises are not a spontaneous phenomenon, and usually occur as a result of inadequate growth in GDP increasing government debt.

Organizational governance

DEFF Research Database (Denmark)

Foss, Nicolai Juul; Klein, Peter G.

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

Metagoverning Collaborative Innovation in Governance Networks

DEFF Research Database (Denmark)

Sørensen, Eva; Torfing, Jacob

2017-01-01

, the current wave of New Public Governance reforms perceives collaboration between relevant and affected actors from the public and private sector as the primary vehicle of public innovation, and tends to see governance networks as potential arenas for collaborative innovation. The new focus on collaborative...... innovation in networks poses a fundamental challenge for public managers, elected politicians, and others aiming to metagovern governance networks. Hence, we claim that a specific metagovernance strategy is needed when the purpose of governance networks is to stimulate efficiency, effectiveness...

Governing sex work in the city

OpenAIRE

Laing, Mary; Cook, Ian

2014-01-01

Sex work is often constructed as an urban "problem". As a result, sex workers, clients and the spaces in which people buy or sell sex are frequently the subject of intervention from those governing cities. This paper considers the ways in which problems and solutions are framed in the wider governance of sex work in cities in the global north. It draws on a range of academic literature to show how the urban governance of sex work takes relational and territorial forms. Governance is relationa...

IT benefits management in local government

DEFF Research Database (Denmark)

Nielsen, Kenneth Møller Porto; Nielsen, Peter Axel; Persson, John Stouby

2012-01-01

Information technology (IT) is increasingly presented as a driving force for service and efficiency improvement in local governments. However, achieving these goals in creating value from IT investments is a significant challenge for local government organizations. Practitioners and researchers...... have proposed numerous approaches to IT benefits management, but our knowledge of current practices and capabilities in local government IT management is still limited. Thus, in this paper we resent an investigation of what characterizes IT benefits management in local government in order to understand...... and improve current practices. Through a comparative case study of two Danish municipalities, we have analyzed the different characteristics of benefits management. Based on this analysis we propose an initial framework for understanding IT benefits management in local government....

An Extended Model of Knowledge Governance

Science.gov (United States)

Karvalics, Laszlo Z.; Dalal, Nikunj

In current times, we are seeing the emergence of a new paradigm to describe, understand, and analyze the expanding "knowledge domain". This overarching framework - called knowledge governance - draws from and builds upon knowledge management and may be seen as a kind of meta-layer of knowledge management. The emerging knowledge governance approach deals with issues that lie at the intersection of organization and knowledge processes. Knowledge governance has two main interpretation levels in the literature: the company- (micro-) and the national (macro-) level. We propose a three-layer model instead of the previous two-layer version, adding a layer of "global" knowledge governance. Analyzing and separating the main issues in this way, we can re-formulate the focus of knowledge governance research and practice in all layers.

Why Mobile Government isn’t successful (yet)

DEFF Research Database (Denmark)

Ohme, Jakob; Seifert, Claudia; Renatus, Rebecca

Mobile Government as a subset of E-Government is part of the Open Government approach of leading countries, like Germany. Since adoption rates among the citizens are still low this study tries to answer the question, what factors concerning the relationship of the government and its citizens migh...

Governance systems in family SMEs: the substitution effects between family councils and corporate governance mechanisms

OpenAIRE

L. Gnan; D. Montemerlo; M. Huse

2015-01-01

The main objective of this paper is to explore the role of family councils vis-à-vis corporate governance mechanisms. Particularly, the paper explores whether family councils perform only their distinctive family governance role or if they also substitute for the roles performed by corporate governance control mechanisms. Based on a sample of 243 Italian family SMEs, our research findings show that the family council partially substitutes the shareholders' meeting and the board of directors i...

G Protein-Coupled Receptor-G-Protein βγ-Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure.

Science.gov (United States)

Kamal, Fadia A; Travers, Joshua G; Schafer, Allison E; Ma, Qing; Devarajan, Prasad; Blaxall, Burns C

2017-01-01

Development of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein-coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G-protein βγ-subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR-Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR-Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor-Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI. Copyright © 2016 by the American Society of Nephrology.

Minority coalition governance in Denmark

DEFF Research Database (Denmark)

Christiansen, Flemming Juul; Pedersen, Helene Helboe

2014-01-01

in this share of coalition agreement-based laws. The analyses are based on unique data on legislative as well as governmental coalition agreements entered by three Danish governments with varying parliamentary strength. This study brings the blooming literature on coalition agreements one step further......Coalition governance is a challenge for political parties because it involves cooperation and compromises between parties that have different political goals and are competitors in political elections. Coalition coordination is crucial for the intra-coalitional cooperation of the governing parties....... A key element in coalition coordination is coalition agreements, which to a varying degree constrain the behaviour of the coalition partners. This article explores the share of laws that were precisely defined in government agreements and/or legislative agreements, and sets out to explain variation...

Organizational Enablers for Project Governance

DEFF Research Database (Denmark)

Müller, Ralf; Shao, Jingting; Pemsel, Sofia

and their relationships to organizational success. Based on these results, the authors discovered that organizational enablers (including key factors such as leadership, governance, and influence of project managers) have a critical impact on how organizations operate, adapt to market fluctuations and forces, and make......While corporate culture plays a significant role in the success of any corporation, governance and “governmentality” not only determine how business should be conducted, but also define the policies and procedures organizations follow to achieve business functions and goals. In their book......, Organizational Enablers for Project Governance, Ralf Müller, Jingting Shao, and Sofia Pemsel examine the interaction of governance and governmentality in various types of companies and demonstrate how these factors drive business success and influence project work, efficiency, and profitability. The data...

Governing for the Common Good.

Science.gov (United States)

Ruger, Jennifer Prah

2015-12-01

The proper object of global health governance (GHG) should be the common good, ensuring that all people have the opportunity to flourish. A well-organized global society that promotes the common good is to everyone's advantage. Enabling people to flourish includes enabling their ability to be healthy. Thus, we must assess health governance by its effectiveness in enhancing health capabilities. Current GHG fails to support human flourishing, diminishes health capabilities and thus does not serve the common good. The provincial globalism theory of health governance proposes a Global Health Constitution and an accompanying Global Institute of Health and Medicine that together propose to transform health governance. Multiple lines of empirical research suggest that these institutions would be effective, offering the most promising path to a healthier, more just world.

Governing EU employment policy

DEFF Research Database (Denmark)

Sørensen, Eva; Triantafillou, Peter; Damgaard, Bodil

2015-01-01

In the European Union (EU), employment policy is a prerogative of the member states. Therefore the EU's ability to govern in this area depends on its capability to involve national governments and relevant stakeholders in a collaborative effort to formulate and implement shared policy objectives....... of collaboration, the implementation phase mainly consists in the less demanding forms of cooperation and coordination....

Australian Government Information Resources

OpenAIRE

Chapman, Bert

2017-01-01

Provides an overview of Australian Government information resources. Features content from Australian Government agency websites such as the Department of Environment and Energy, Department of Defence, Australian National Maritime Museum, ANZAC Memorial in Sydney, Department of Immigration & Border Protection, Australian Bureau of Statistics, Australian Dept. of Agriculture and Water Resources, Australian Parliament, Australian Treasury, Australian Transport Safety Board, and Australian Parl...

Keberhasilan Implementasi Elektronik Government Berdasarkan Persepsi Pengguna

Directory of Open Access Journals (Sweden)

Yuni Rimawati

2012-08-01

Full Text Available This research verifies the success of e-Government that is implemented by directorate general of taxes as state institution based on user satisfaction. Seven variables investigated in this research are the usability of e-Government, information quality of e-Government, service quality of e-Government, trust of the government institution, trust of the internet, and Intention to Use Frequently e-Government. The measurement of independent variables that used in this research is based on Barnes and Vidgen (2006 and Bélangerdan Carter (2008. The measurement of dependent variable (user satisfaction based on Xiao dan Dasgupta (2002 which modified with Verdegem and Verleye (2009.

22 CFR 204.43 - Governing law.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 204.43 Section 204.43 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Administration § 204.43 Governing law. This Guaranty shall be governed by and construed in accordance with the laws of...

Shared Governance in the Modern University

Science.gov (United States)

Taylor, Mark

2013-01-01

A governance model is developed in which university governance is shared between the academic and governing bodies and is coordinated by the university executive. Viewing the university as a professional service organisation, and noting the importance of developing a flexible culture within a shifting, marketised external environment, it is argued…

Joint ventures between industry and government

International Nuclear Information System (INIS)

Vant, T.R.

1991-01-01

Joint venture projects undertaken between government and industry in western Canada are reviewed. The first significant involvement of the Alberta government was with the Syncrude oil sands project. In 1974, one of the original participants, Atlantic Richfield, pulled out of Syncrude for financial reasons. After a government review and search for replacement participation, three provincial governments took equity positions in the project. The Syncrude project has since had a very significant impact on Alberta and Canada in terms of oil production, employment, investment, and profits. The Other Six Leases Operation (OSLO), the OSLO New Ventures Project, and the Lloydminster Bi-Provincial Upgrader would also not have advanced to their present stages of development without government participation. Since oil sand/heavy oil development requires significant capital investment over long lead times, and since there are few private companies that can undertake such a commitment, government assistance is often required. It also makes sense for governments to share upfront risk in such projects for both the long-term economic gain and such immediate benefits as job creation and energy supply security. An industry/government joint venture provides a means of getting large, inherently economic projects such as oil sands developments under way while protecting taxpayers' interests. The success of such a joint venture depends not only on the financing brought to the project but also on the expertise, decision making capability, and balanced management of regulatory and policy issues

Government-Driven Participation and Collective Intelligence: A Case of the Government 3.0 Initiative in Korea

Directory of Open Access Journals (Sweden)

Taewoo Nam

2016-10-01

Full Text Available The Park Geun-hye Administration of Korea (2013–2017 aims to increase the level of transparency and citizen trust in government through the Government 3.0 initiative. This new initiative for public sector innovation encourages citizen-government collaboration and collective intelligence, thereby improving the quality of policy-making and implementation and solving public problems in a new way. However, the national initiative that identifies collective intelligence and citizen-government collaboration alike fails to understand what the wisdom of crowds genuinely means. Collective intelligence is not a magic bullet to solve public problems, which are called “wicked problems”. Collective deliberation over public issues often brings pain and patience, rather than fun and joy. It is not so easy that the public finds the best solution for soothing public problems through collective deliberation. The Government 3.0 initiative does not pay much attention to difficulties in gathering scattered wisdom, but rather highlights uncertain opportunities created by collective interactions and communications. This study deeply discusses the weaknesses in the logic of, and approach to, collective intelligence underlying the Government 3.0 initiative in Korea and the overall influence of the national initiative on participatory democracy.

The Janus Face of Governance Theory

DEFF Research Database (Denmark)

Sørensen, Eva; Torfing, Jacob

2017-01-01

While the main current in the growing research on governance has praised its virtues, a critical undertow has insisted that governance carries the danger of depoliticization and democratic decline. Chapter 2 aims to complicate things by arguing that interactive forms of governance intending...... science perspective has a sharper eye for the political choices, conflicts, and power struggles. If the political science perspective has a blind spot, it concerns the role of elected politicians in the exercise of political meta-governance. That role is further developed towards the end of the chapter...