890 resultados para leader peptidases
Resumo:
Solo Exhibition, MacKenzie Art Gallery, Regina, Canada, The project engages with current issues around art production and food provision, catastrophe and agriculture, through the medium of a performance installation. Drawing on some of the characteristics of post dramatic theatre, the project aims to develop a new visual narratology for a contemporary art performance. A large scale video installation and construction features both as an installation site and performance set, explores the relationship between performance and food provision, looking at how changes to the organic world, the world of vibrant and edible matter might affect the way we make art. Developed and produced in collaboration with Canadian company Curtain Razors and funded by grants from Canada Council for the Arts, Saskatchewan Arts Board, the project was first commissioned by Curtain Razors and the MacKenzie Art Gallery where it was shown as a major solo exhibition as part of a series of other international programming (including artists such Guy Ben-Ner and Ron Mueck). The project was then included in the 4th Moscow Biennial as part of the landmark ‘Independent’ exhibition at the Art Arsenal in 2011. The project is planned to tour to varies other international venues throughout 2012/13. The exhibition has been reviewed by Gregory Beatty in Prairie Dog, Regina, by at the The Leader Post, The CBC French Canadian Television. Canadian writer curator Timothy Long artist and curator Elwood Jimmy have produced critical essays of the work, which will feature in a major new book, edited by Susanne Clausen, which is expected to be published in 2012. (OnCurating Publications).
Resumo:
Research undertaken through significant public art commission. The researchers were both artists were selected separately by Dr Penelope Curtis of Tate and then the shortlist was awarded through competition (peer reviewed by Critics and Artist in Germany) part of the Heidenheim Sculpture Biennial, Germany (€18K). The work was realised by two companies in Heidenheim. Where is Heidenheim? was based within the Heidenheim Zietung newspaper[HZ] and drew together a site of a local paper in a small town in Germany with other local International papers; Wendover Times – Utah, USA;, Limerick Leader, Ireland; Free Imphal Press, Manipur, India; Hibr, Lebanon; Namibia Times, Namibia and The Countryman, Tasmania, Australia. Each of these papers ran a story showing a sign erected onto HZ in Heidenheim, which was subsequently printed inside HZ itself – linking together sites and local voices. Project research identifying global partners was conducted through the management of a PhD research student from the BU Media School - Venkata Vermuri. The work for both artists expands the context of their research into the impact of global networks on public art, and the traditions and norms of public art being confined to single ‘geographical’ sites. This research indicates the potential for media as a common public space that can also be used.
Resumo:
This article examines the problems of elite capture in community driven development (CDD). Drawing on two case studies of non-governmental organisation (NGO) intervention in rural Mozambique, the authors consider two important variables – 1) the diverse and complex contributions of local elites to CDD in different locations, and 2) the roles that non-elites play in monitoring and controlling leader activities – to argue that donors should be cautious about automatically assuming the prevalence of malevolent patrimonialism and its ill-effects in their projects. This is because the ‘checks and balances’ on elite behaviour that exist within locally-defined and historically-rooted forms of community-based governance are likely to be more effective than those introduced by the external intervener.
Resumo:
The enzymatic activity of peptidases must be tightly regulated to prevent uncontrolled hydrolysis of peptide bonds, which could have devastating effects in biological systems. Peptidases are often generated as inactive propeptidases, secreted with endogenous inhibitors or they are compartmentalized. Propeptidases become active after proteolytic removal of N-terminal activation peptides by other peptidases. Some peptidases only become active towards substrates only at certain pHs, thus confining activity to specific compartments or conditions. This review discusses the different roles proteolysis plays in regulating G protein-coupled receptors (GPCRs). At the cell-surface, certain GPCRs are regulated by the hydrolytic inactivation of bioactive peptides by membrane-anchored peptidases, which prevents signaling. Conversely, cell-surface peptidases can also generate bioactive peptides that directly activate GPCRs. Alternatively, cell-surface peptidases activated by GPCRs, can generate bioactive peptides to cause transactivation of receptor tyrosine kinases, thereby promoting signaling. Certain peptidases can signals directly to cells, by cleaving GPCR to initiate intracellular signaling cascades. Intracellular peptidases also regulate GPCRs; lysosomal peptidases destroy GPCRs in lysosomes to permanently terminate signaling and mediate downregulation; endosomal peptidases cleave internalized peptide agonists to regulate GPCR recycling, resensitization and signaling; and soluble intracellular peptidases also participate in GPCR function by regulating the ubiquitination state of GPCRs, thereby altering GPCR signaling and fate. Although the use of peptidase inhibitors has already brought success in the treatment of diseases such as hypertension, the discovery of new regulatory mechanisms involving proteolysis that control GPCRs may provide additional targets to modulate dysregulated GPCR signaling in disease.
Resumo:
Neuropeptide signalling at the plasma membrane is terminated by neuropeptide degradation by cell-surface peptidases, and by beta-arrestin-dependent receptor desensitization and endocytosis. However, receptors continue to signal from endosomes by beta-arrestin-dependent processes, and endosomal sorting mediates recycling and resensitization of plasma membrane signalling. The mechanisms that control signalling and trafficking of receptors in endosomes are poorly defined. We report a major role for endothelin-converting enzyme-1 (ECE-1) in controlling substance P (SP) and the neurokinin 1 receptor (NK(1)R) in endosomes of myenteric neurones. ECE-1 mRNA and protein were expressed by myenteric neurones of rat and mouse intestine. SP (10 nM, 10 min) induced interaction of NK(1)R and beta-arrestin at the plasma membrane, and the SP-NK(1)R-beta-arrestin signalosome complex trafficked by a dynamin-mediated mechanism to ECE-1-containing early endosomes, where ECE-1 can degrade SP. After 120 min, NK(1)R recycled from endosomes to the plasma membrane. ECE-1 inhibitors (SM-19712, PD-069185) and the vacuolar H(+)ATPase inhibitor bafilomycin A(1), which prevent endosomal SP degradation, suppressed NK(1)R recycling by >50%. Preincubation of neurones with SP (10 nM, 5 min) desensitized Ca(2+) transients to a second SP challenge after 10 min, and SP signals resensitized after 60 min. SM-19712 inhibited NK(1)R resensitization by >90%. ECE-1 inhibitors also caused sustained SP-induced activation of extracellular signal-regulated kinases, consistent with stabilization of the SP-NK(1)R-beta-arrestin signalosome. By degrading SP and destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling endocytic signalling and trafficking of the NK(1)R: promoting resensitization of G protein-mediated plasma membrane signalling, and terminating beta-arrestin-mediated endosomal signalling.
Resumo:
Agonist-induced internalization of somatostatin receptors (ssts) determines subsequent cellular responsiveness to peptide agonists and influences sst receptor scintigraphy. To investigate sst2A trafficking, rat sst2A tagged with epitope was expressed in human embryonic kidney cells and tracked by antibody labeling. Confocal microscopical analysis revealed that stimulation with sst and octreotide induced internalization of sst2A. Internalized sst2A remained sequestrated within early endosomes, and 60 min after stimulation, internalized sst2A still colocalized with beta-arrestin1-enhanced green fluorescence protein (EGFP), endothelin-converting enzyme-1 (ECE-1), and rab5a. Internalized (125)I-Tyr(11)-SST-14 was rapidly hydrolyzed by endosomal endopeptidases, with radioactive metabolites being released from the cell. Internalized (125)I-Tyr(1)-octreotide accumulated as an intact peptide and was released from the cell as an intact peptide ligand. We have identified ECE-1 as one of the endopeptidases responsible for inactivation of internalized SST-14. ECE-1-mediated cleavage of SST-14 was inhibited by the specific ECE-1 inhibitor, SM-19712, and by preventing acidification of endosomes using bafilomycin A(1). ECE-1 cleaved SST-14 but not octreotide in an acidic environment. The metallopeptidases angiotensin-1 converting enzyme and ECE-2 did not hydrolyze SST-14 or octreotide. Our results show for the first time that stimulation with SST-14 and octreotide induced sequestration of sst2A into early endosomes and that endocytosed SST-14 is degraded by endopeptidases located in early endosomes. Furthermore, octreotide was not degraded by endosomal peptidases and was released as an intact peptide. This mechanism may explain functional differences between octreotide and SST-14 after sst2A stimulation. Moreover, further investigation of endopeptidase-regulated trafficking of neuropeptides may result in novel concepts of neuropeptide receptor inactivation in cancer diagnosis.
Resumo:
Although cell surface metalloendopeptidases degrade neuropeptides in the extracellular fluid to terminate signaling, the function of peptidases in endosomes is unclear. We report that isoforms of endothelin-converting enzyme-1 (ECE-1a-d) are present in early endosomes, where they degrade neuropeptides and regulate post-endocytic sorting of receptors. Calcitonin gene-related peptide (CGRP) co-internalizes with calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), beta-arrestin2, and ECE-1 to early endosomes, where ECE-1 degrades CGRP. CGRP degradation promotes CLR/RAMP1 recycling and beta-arrestin2 redistribution to the cytosol. ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/RAMP1 recycling and resensitization, whereas ECE-1 overexpression has the opposite effect. ECE-1 does not regulate either the resensitization of receptors for peptides that are not ECE-1 substrates (e.g., angiotensin II), or the recycling of the bradykinin B(2) receptor, which transiently interacts with beta-arrestins. We propose a mechanism by which endosomal ECE-1 degrades neuropeptides in endosomes to disrupt the peptide/receptor/beta-arrestin complex, freeing internalized receptors from beta-arrestins and promoting recycling and resensitization.
Resumo:
The Sarkozy presidency is shot through with paradox and contrast: between a well-elected president swiftly loathed by most voters; a ‘hyper-president’ who probably weakened the office; a talented party leader who lost effective control of his party; a right-wing president who was readily compared to Tony Blair; and an ambitious reformer who promised a clean break with the indecision of his two predecessors but whose record was more timid than his rhetoric. This article interprets Sarkozy’s record in the context of the presidential office, the specific circumstances of his presidency, and of the president’s own personality, skills and shortcomings.
Resumo:
Purpose – The focus of extant strategy literature is on for-profit organisations and within these group public organisations. There are other forms of organisations and following the deep recession of 2008 there is greater interest in other forms of organisation. In this case study and interview the aim is to examine strategy, strategic decisions and strategic management of a not-for-profit provident. Design/methodology/approach – The paper draws on documentary evidence and a semi-structured interview with Ray King, chief executive of Bupa. The perspective of CEO is key in strategy and such perspectives are relatively rarer. Findings – Bupa invests its surplus to provide better healthcare. Free from the pressures of quarterly reporting and shareholders it can pursue long-term value creation for members rather than short-term surpluses. Research limitations/implications – The case study and interview offers a unique insight into strategy-making within a successful mutual provident that has grown organically and externally becoming an international leader in health insurance. Originality/value – This case study sheds light on strategy-making within a not-for-profit provident that has diversified and grown significantly over the past six decades. Furthermore, very few case studies offer insight into the thinking of a chief executive who has successfully managed a business in a turbulent environment.
Resumo:
The Advanced Along-Track Scanning Radiometer (AATSR) was launched on Envisat in March 2002. The AATSR instrument is designed to retrieve precise and accurate global sea surface temperature (SST) that, combined with the large data set collected from its predecessors, ATSR and ATSR-2, will provide a long term record of SST data that is greater than 15 years. This record can be used for independent monitoring and detection of climate change. The AATSR validation programme has successfully completed its initial phase. The programme involves validation of the AATSR derived SST values using in situ radiometers, in situ buoys and global SST fields from other data sets. The results of the initial programme presented here will demonstrate that the AATSR instrument is currently close to meeting its scientific objectives of determining global SST to an accuracy of 0.3 K (one sigma). For night time data, the analysis gives a warm bias of between +0.04 K (0.28 K) for buoys to +0.06 K (0.20 K) for radiometers, with slightly higher errors observed for day time data, showing warm biases of between +0.02 (0.39 K) for buoys to +0.11 K (0.33 K) for radiometers. They show that the ATSR series of instruments continues to be the world leader in delivering accurate space-based observations of SST, which is a key climate parameter.
Resumo:
We apply an alternating proposals protocol with a confirmation stage as a way of solving a Prisoner’s Dilemma game. We interpret players’ proposals and (no) confirmation of outcomes of the game as a tacit communication device. The protocol leads to unprecedented high levels of cooperation in the laboratory. Assigning the power of confirmation to one of the two players alone, rather than alternating the role of a leader significantly increases the probability of signing a cooperative agreement in the first bargaining period. We interpret pre-agreement strategies as tacit messages on players’ willingness to cooperate and on their beliefs about the others’ type.
Resumo:
We suggest an alternating proposals protocol with a confirmation stage as a way of solving a Prisoner's Dilemma game. We interpret players' proposals and (no) confirmation of outcomes of the game as a tacit communication device. The protocol leads to unprecedented high levels of cooperation in the laboratory. Assigning the power of confirmation to one of the two players alone, rather than alternating the role of a leader significantly increases the probability of cooperation in the first bargaining period. We interpret pre-agreement strategies as tacit messages on players' willingness to cooperate and as signals pursuing individualistic objectives like publicizing one's bargaining abilities or eliciting those of the opponent.
Resumo:
What determines the emergence and survival of democracy? The authors apply extreme bounds analysis to test the robustness of fifty-nine factors proposed in the literature, evaluating over three million regressions with data from 165 countries from 1976 to 2002. The most robust determinants of the transition to democracy are gross domestic product (GDP) growth (a negative effect), past transitions (a positive effect), and Organisation for Economic Co-operation and Development membership (a positive effect). There is some evidence that fuel exporters and Muslim countries are less likely to see democracy emerge, although the latter finding is driven entirely by oil-producing Muslim countries. Regarding the survival of democracy, the most robust determinants are GDP per capita (a positive effect) and past transitions (a negative effect). There is some evidence that having a former military leader as the chief executive has a negative effect, while having other democracies as neighbors has a reinforcing effect.
Resumo:
This article investigates the contested ideology of al-Qaeda through an analysis of Osama bin Ladin’s writings and public statements issued between 1994 and 2011, set in relation to the development of Islamic thought and changing socio-political realities in the late nineteenth and twentieth centuries. Challenging popular conceptions of Wahhabism and the “Salafi jihad”, it reveals an idealistic, Pan-Islamic sentiment at the core of his messages that is not based on the main schools of Islamic theology, but is the result of a crisis of meaning of Islam in the modern world. Both before and after the death of al-Qaeda’s iconic leader, the continuing process of religious, political and intellectual fragmentation of the Muslim world has led to bin Ladin’s vision for unity being replaced by local factions and individuals pursuing their own agendas in the name of al-Qaeda and Islam.
Resumo:
Destructive leadership behaviour often results in damage to the organisations that the individual is entrusted to lead. Although accurately pinpointing the type of destructive behaviour is difficult, this article seeks to offer suggestions as to why leaders spiral into such unattractive behaviour. After reviewing the literature, this paper highlights four drivers for destructive ways that people act based on detailed qualitative scenarios that involve how those who experienced such behaviour reacted and felt. The study reveals a noticeable human experience from which nobody can escape, and offers understanding of the study participants’ experiences. Out of respect to the participants, the authors keep their identity anonomous. We drew our subjects from a cross-section of organisations that function internationally within one area of the manufacturing industry. The article presents a model comprising two dimensions: 1) the leader’s attitude to the organisation he or she leads and 2) adequacy of his or her leadership capabilities. The models offer us understanding of the drivers of the destructive actions that the leader exhibits. Understanding allows us to provide managers with tactical methods to protect them against destructive behaviour and help them lessen the worst aspects of destructive behaviour in both their colleagues and themselves.