17 results on '"Wong, Cecilia"'
Search Results
2. Activation of STAT3 by Gαs Distinctively Requires Protein Kinase A, JNK, and Phosphatidylinositol 3-Kinase
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Liu, A.M.F., Lo, Kin H., Wong, Cecilia S.S., Morris, Christina, Wise, Helen, Wong, Yung Hou, Liu, A.M.F., Lo, Kin H., Wong, Cecilia S.S., Morris, Christina, Wise, Helen, and Wong, Yung Hou
- Abstract
Signal transducer and activator of transcription 3 (STAT3) can be stimulated by several Gs-coupled receptors, but the precise mechanism of action has not yet been elucidated. We therefore examined the ability of GαsQ226L (GαsQL), a constitutively active mutant of Gαs, to stimulate STAT3 Tyr705 and Ser727 phosphorylations in human embryonic kidney 293 cells. Apart from GαsQL, the stimulation of Gαs by cholera toxin or β2-adrenergic receptor and the activation of adenylyl cyclase by forskolin, (Sp)-cAMP, or dibutyryl-cAMP all promoted both STAT3 Tyr705 and Ser727 phosphorylations. Moreover, the removal of Gαs by RNA interference significantly reduced the β2-adrenergic receptor-mediated STAT3 phosphorylations, denoting its capacity to regulate STAT3 activation by a G protein-coupled receptor. The possible downstream signaling molecules involved were assessed by using specific inhibitors and dominant negative mutants. Induction of STAT3 Tyr705 and Ser727 phosphorylations by GαsQL was suppressed by inhibition of protein kinase A, Janus kinase 2/3, Rac1, c-Jun N-terminal kinase (JNK), or phosphatidylinositol 3-kinase, and a similar profile was observed in response to β2-adrenergic receptor stimulation. In contrast to the Gα16-mediated regulation of STAT3 in HEK 293 cells (Lo, R. K., Cheung, H., and Wong, Y. H. (2003) J. Biol. Chem. 278, 52154-52165), the Gαs-mediated responses, including STAT3-driven luciferase activation, were resistant to inhibition of phospholipase Cβ. Surprisingly, Gαs-mediated phosphorylation at Tyr705, but not at Ser727, was resistant to inhibition of c-Src, Raf-1, and MEK1/2 as well as to the expression of dominant negative Ras. Therefore, as with other Gα-mediated activations of STAT3, the stimulatory signal a
- Published
- 2006
3. An approach to parameter sensitivity analyses in model assessment
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Wong, Cecilia Sau Yen and Wong, Cecilia Sau Yen
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- 2006
4. A study of the purinergic receptors : A1R and P2Y1R in their homodimerization and receptor signaling
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Wong, Cecilia Sui Si and Wong, Cecilia Sui Si
- Abstract
Despite previous work done in the rat hippocampal neuron (Ikeuchi et al., 1996) and in rat portal vein (Guibert et al., 1998), details of the physiological functions of the purinergic receptor still remain unclear. In this study, further insights into the significance of P1/P2 receptor coexistence may be obtained by studying the receptor regulation and signaling between them. Donor photobleaching FRET was used to show homodimerization of the purinergic P2Y1 (P2Y1R) and the adenosine A1 receptors (A1R) in living cells. FRET is dependent on the molecular proximity and energy transfer between the energy donor FITC-anti-Myc, and acceptor Cy3-anti-Myc, making it possible to study the interactions between the epitope-tagged P2Y1 and A1 receptors. In the presence of a Gi-linked A1R and a Gq-linked P2Y1R, the rate of ERK phosphorylation was brought on earlier in a time-course study when co-treated with both agonists as compared to treated with 2-MeSADP alone. Cross talk between A1R and P2Y1R must have contributed to the augmentation in signals which is a common occurrence between Gi- and Gq-linked receptors where synergism often occurs. A1R and P2Y1R transfected cells did not show synergistic activation of JNK and p38. GPCR down-regulation includes agonist induced desensitization and receptor internalization. These regulations were examined using the epitope-tag Myc-P2Y1R construct. Transiently transfected HEK293 cells when pretreated with 2-MeSADP can induce desensitization, thereby diminished the subsequent 2-MeSADP stimulation of Ca2+ mobilization. Myc-P2Y1R when transiently expressed in HEK293 cells and visualized with FITC-anti-Myc showed membrane distribution but upon 2-MeSADP treatment, the receptor can internalize into the cytosol of the cells when tracked against time. Overall, the complexity of GPCRs regulation was studied by looking at the homodimerization of P2Y1R and A1R and since they were previously shown to heterodimerize, their signaling responses and their
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- 2005
5. Regulation of P2Y1 Receptor: Signal Transduction, Dimerization, Desensitization and Internalization
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Choi, Chi Yan, Wong, Cecilia S.S., Barnard, E.A., Tsim, Karl Wah Keung, Choi, Chi Yan, Wong, Cecilia S.S., Barnard, E.A., and Tsim, Karl Wah Keung
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- 2005
6. Replacement of the α5 helix of Gα16 with Gαs-specific sequences enhances promiscuity of Gα16 toward Gs-coupled receptors
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Hazari Anjali Ajaykumar, Lowes, Vicki L., Chan, Jasmine H.P., Wong, Cecilia S.S., Ho, Maurice K.C., Wong, Yung Hou, Hazari Anjali Ajaykumar, Lowes, Vicki L., Chan, Jasmine H.P., Wong, Cecilia S.S., Ho, Maurice K.C., and Wong, Yung Hou
- Abstract
G16 can couple indiscriminately to a large number of G protein-coupled receptors (GPCRs), making it a prime candidate as a universal adaptor for GPCRs. In order to increase the promiscuity of Gα 16, three chimeras incorporating increasing lengths of Gs-specific residues (25, 44 or 81 residues) into the C-terminus of Gα16 were constructed and named 16s25, 16s44 and 16s81, respectively. The chimeras were examined for their ability to mediate receptor-induced stimulation of phospholipase C (PLC) and Ca2+ mobilization. 16s25 was more effective than 16s44 and 16s81 at coupling to Gs-linked receptors. 16s25 coupled productively to 10 different Gs-coupled receptors examined and, for 50% of these receptors, 16s25-mediated PLC activities were higher than those mediated via Gα16. Similar results were observed for agonist-induced Ca2+ mobilizations. These results show that incorporating the α5 helix of Gαs into Gα16 can increase the promiscuity of 16s25 towards Gs-coupled receptors. © 2003 Elsevier Inc. All rights reserved.
- Published
- 2004
7. Gα16/z chimeras efficiently link a wide range of G protein-coupled receptors to calcium mobilization
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Liu, A.M.F., Ho, Maurice K.C., Wong, Cecilia S.S., Chan, Jasmine H.P., Pau, Anson H.M., Wong, Yung Hou, Liu, A.M.F., Ho, Maurice K.C., Wong, Cecilia S.S., Chan, Jasmine H.P., Pau, Anson H.M., and Wong, Yung Hou
- Abstract
G protein-coupled receptors (GPCRs) represent a class of important therapeutic targets for drug discovery. The integration of GPCRs into contemporary high-throughput functional assays is critically dependent on the presence of appropriate G proteins. Given that different GPCRs can discriminate against distinct G proteins, a universal G protein adapter is extremely desirable. In this report, the authors evaluated two highly promiscuous Gα16/z chimeras, 16z25 and 16z44, for their ability to translate GPCR activation into Ca2+ mobilization using the fluorescence imaging plate reader (FLIPR) and aequorin. A panel of 24 Gs- or Gi-coupled receptors was examined for their functional association with the Gαl6/z chimeras. Although most of the GPCRs tested were incapable of inducing Ca2+ mobilization upon their activation by specific agonists, the introduction of 16z25 or 16z44 allowed all of these GPCRs to mediate agonist-induced Ca2+ mobilization. In contrast, only 16 of the GPCRs tested were capable of using Gα16 to mobilize intracellular Ca2+. Analysis of dose-response curves obtained with the δ-opioid, dopamine D1, and Xenopus melatonin Mel1c receptors revealed that the Gα16/z chimeras possess better sensitivity than Gα16 in both the FLIPR and aequorin assays. Collectively, these studies help to validate the promiscuity of the Gα16/z chimeras as well as their application in contemporary drug-screening assays that are based on ligand-induced Ca2+ mobilization. © 2003 The Society for Biomolecular Screening.
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- 2003
8. The β6/α5 regions of Gαi2 and GαoA increase the promiscuity of Gα16 but are insufficient for pertussis toxin-catalyzed ADP-ribosylation
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Wong, Cecilia S.S., Ho, Maurice K.C., Wong, Yung Hou, Wong, Cecilia S.S., Ho, Maurice K.C., and Wong, Yung Hou
- Abstract
Replacement of beta6/alpha5 region at the C-tenninus on Galpha(16) with Galpha(16)-specific residues has been shown to broaden the promiscuity of Galpha(16). Here, we substituted the last 44 residues of Galpha(16) with the corresponding region from either Galpha(i2) or Galpha(oA) (16i44 and 16o44). 16i44 and 16o44 chimeras were more effective than Galpha(16) at coupling to G(i)-linked delta-opioid, mu-opioid, and Xenopus melatonin MT1c receptors when coexpressed in green monkey fibroblast (COS-7) cells. 16o44, but not 16o44, also enhanced the formyl peptide-induced stimulation of phospholipase C activity. Both chimeras were resistant to pertussis toxin-catalyzed [P-32]ADP-ribosylation, despite the fact that pertussis toxin partially inhibited the chimera-mediated stimulation of phospholipase Cbeta. The use of Galpha(t1) as a Gbetagamma scavenger revealed that the pertussis toxin-sensitivity can be attributed to endogenous Gbetagamma subunits released from G(i/o). Although incorporation of a Galpha(i)-like beta6/alpha5 region into the C-terminus of Galpha(16) increases its promiscuity, this region is not sufficient to support recognition by pertussis toxin. (C) 2003 Elsevier B.V. All rights reserved.
- Published
- 2003
9. Selected mutations of the a5 helix of Ga16 improves the coupling of Gi-linked receptor
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Ho, Maurice K.C., Chan, Jasmine H.P., Wong, Cecilia S.S., Wong, Yung Hou, Ho, Maurice K.C., Chan, Jasmine H.P., Wong, Cecilia S.S., and Wong, Yung Hou
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- 2001
10. Replacement of the C-terminal residues of Ga16 with Gai2 or Gao1 residues enhances its promiscuity for receptor recognition.
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Wong, Cecilia S.S., Pau, Anson H.M., Wong, Yung Hou, Wong, Cecilia S.S., Pau, Anson H.M., and Wong, Yung Hou
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- 2001
11. A Map for England: Spatial expression of government policies and programmes
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Wong, Cecilia, Baker, Mark, Hincks, Stephen, Schulze-Baing, Andreas, Webb, Brian, Wong, Cecilia, Baker, Mark, Hincks, Stephen, Schulze-Baing, Andreas, and Webb, Brian
12. Housing and neighbourhood monitor 2011: Fragility and recovery
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Wong, Cecilia, Gibb, Ken, McGreal, Stanley, Webb, Brian, Leishman, Chris, Blair, Neale, Hincks, Stephen, MacIntyre, Sean, Wong, Cecilia, Gibb, Ken, McGreal, Stanley, Webb, Brian, Leishman, Chris, Blair, Neale, Hincks, Stephen, and MacIntyre, Sean
13. Economic linkages of China's small towns : urban-rural integration in a learning economy
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Qiao, Miao, Deas, Iain, and Wong, Cecilia
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338.9 ,economic linkage ,learning economy ,small town ,China ,urban-rural integration - Abstract
As the problem of urban-rural inequality in China becomes increasingly severe, urban-rural integration has become a hot topic among both researchers and policymakers. However, to achieve urban-rural integration faces the challenges from dualism in institutional arrangements, diversity in territorial contexts, and uncertainty in development environments. In response to these challenges, this research employs the idea of ‘economic linkages of small towns’ to develop a rural-centred, place-based, and process-oriented approach towards urban-rural integration. This research examines the functions, patterns, and dynamics of economic linkages of small towns under the wider economic-spatial restructuring process brought by rapid economic growth and urbanisation in China. More specifically, this research explores the implications of small towns’ economic linkages for integrated development of urban and rural areas. Based on the idea of ‘problem-solving’, this research develops the conceptual framework of ‘Learning-based Territorial Economic System (TES)’ which includes ‘knowledge system’, ‘organisational system’, and ‘territorial system’. This conceptual framework conceptualises ‘economic linkages’ as interactions between economic actors who participated in various ‘interactive situations’ in solving local development problems. This research carried out two case studies of successful small town and rural development in Kunshan, Jiangsu and Shunde, Guangdong. The empirical findings demonstrate that economic linkages are crucial in identifying local development problems, getting access to key economic resources, and coordinating economic activities in uncertain circumstances. Based on the empirical findings, this research develops two development models of Learning-based TES – the Kunshan Model and the Shunde Model – as coherent systems of economic linkages in problem-solving processes. Explicitly, the Kunshan Model features interactive situations of competitive positioning, elite coalition-building, and synchronised operation and the Shunde Model features interactive situations of reflective monitoring, skill matching, and communicative mediation. In application of these two development models, this research formulates a ‘3-step formula’ as key policy implication, including assessment, experiment, and institutionalisation. Such ‘3-step formula’ can contribute to build up local problem-solving capacities that lead to more substantial urban-rural integration.
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- 2016
14. Urban street design in modern China : standards, practices and outcomes
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Zhang, Yi, Wong, Cecilia, and Hebbert, Michael
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388.4 ,urban street design ,standards ,practices ,paradigm shift - Abstract
This thesis investigates and discusses the current design approaches and development trends of urban streets in China. As the methodological focus, multiple case studies and interviews are used to examine actual street design practice to identify the development policy bias of local governments. Since the 1990s, the great economic achievement in most Chinese cities has evoked significant growth in the number of automobiles, as well as the increasingly serious problems of road casualties and congestion. The traffic-engineering-based design approach which used to be widely adopted and implemented in western countries has dominated the development patterns of urban streets in modern China. The conventional paradigm exclusively focuses on the traffic function in urban streets resulting in morphological changes to the urban circulation environment and keeps on neglecting non-vehicular movement and non-traffic needs. The automobile- dominated urban circulation environment has had negative economic, social and public health impacts. Thus, a paradigm shift which calls for a more inclusive design approach for urban streets which balances functions of place and movement is urgently needed in China. To determine the challenges and opportunities for the new paradigm, this research identifies the cultural, political and technical factors for the traffic-centred design trends and the policy bias. Based on this, policy recommendations and an agenda for revolutionary change for achieving better design practice for urban streets in post-modern China are suggested.
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- 2013
15. Federalism and the institutional dynamics of intergovernmental spatial policy coordination in Canada
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Webb, Brian Norman, Deas, Iain, and Wong, Cecilia
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321.02 ,Spatial planning ,Federalism ,Policy coordination ,Canada - Abstract
This thesis discusses the governmental institutional dynamics that structure the formulation and coordination of spatial policy within the federal Canadian intergovernmental system and presents methods to improve it. The research utilises the three traditions of new institutionalism - historical, rational choice and sociological - to develop a crosscutting assessment of intergovernmental spatial policy coordination. An embedded case study approach is then used to discuss intergovernmental spatial policy coordination between the governments of Canada, British Columbia, Alberta and Saskatchewan. Research findings highlight the uniqueness of the institutional environments that exist within each government, and to a lesser extent each department, which structure policymakers’ understandings of intergovernmental spatial policy coordination. Policymakers demonstrate a distinct awareness of spatial issues, but they are often constrained in their ability formally to articulate this in the development of public policy, particularly in relation to intergovernmental interactions. The decentralised federal nature of Canada is shown to be a highly influential reason for this, with issues of history, equity, politics and strong regional government cultures playing important roles in impeding intergovernmental spatial policy coordination. The thesis explores these constraints, discussing how both formal and informal institutional structures interact to discourage the use of spatial policy, and discusses the ways in which intergovernmental spatial policy coordination could be enhanced in the specific context of Canada. The institutional framework developed in this research is shown to be a useful method for conceptualising the competing federal principles of unity and diversity in the study of intergovernmental spatial policy coordination. Ultimately this thesis argues that while intergovernmental spatial policy coordination is poorly developed in Canada, policymaker awareness of spatial issues influences the decision-making processes employed to develop and coordinate public policy.
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- 2011
16. Towards the development of a spatial planning framework for rural development in China : a case study of Jiangsu Province
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Qian, Hui, Wong, Cecilia, and Baker, Mark
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307.1 ,spatial planning ,rural development ,China - Abstract
After being neglected for two decades, rural areas in China are experiencing another wave of reform. There has been increasing attention from central government on rural issues and a series of rural resurgence policies were published with a central idea of ‘urban-rural integration and New Socialist Rural Construction Programme’ (State Council, 2010b). Planning as a policy tool to guide development has just began to cover rural areas in China. There is a need to develop a framework, both theoretically robust and deliverable, to guide rural planning in China. ‘Spatial planning’ has been widely adopted as a planning approach in Western Europe, including the UK, to achieve sustainable development. Hence, the research aims to use the concept of ‘spatial planning’ to identify potential ways to integrate rural areas into the complex planning system that currently exists in China. The research was carried out through a case study approach in three municipal cities in Jiangsu province, China. The newly developed rural planning system in Jiangsu province mainly focuses on the development control of towns and villages, physical landuse regulation and the renovation of settlements through town and village distribution planning and village planning. There is a lack of development planning for rural areas. The findings also show that the new urban and rural planning system generally fails to integrate urban and rural development, though in some developed areas more attention has been put on urban-rural integration planning. Moreover, it is found that, in many areas, the new urban and rural planning framework tends to be urban-centre-led and economically driven, which has led to the loss of rural landscape and characteristics. The research also identifies the weakness of planning at the local scale in coordinating policies and projects of different sectors. In addition, local government plays a leading role in the making and delivery of rural planning in China and, in some areas, local government activities in rural development and planning are much more a political response to the national and provincial government’s policy rather than the local demands. Based on these findings, the research provides some policy recommendations for modifying the current rural planning framework in China to overcome these problems in the short and long term by making reference to some of the key ideas of the spatial planning approach.
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- 2011
17. The institutional structure of residential development industry in Malaysia : a private developers' perspective
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Foo, Lee Hoon Ruth, Wong, Cecilia, and Barker, Adam
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363.5 - Abstract
This research is intended to examine the institutional structure of the Malaysian residential development industry with a specific focus on the nature of interaction between developers and the state. On this basis, this thesis aims to examine the institutional role of developers and their interaction with the state to improve the housing delivery system. Ball’s (1998;1986) Structure of Provision theory (SoP) and Wong and Madden’s (2000) North West Housing Assessment model were adapted to explore developers’ views and aspirations in various aspects of the residential industry in Malaysia. Case study research with extreme case scenarios were carried out in Kuala Lumpur and Johor to ascertain robust findings to contrast and compare. The institution of the Malaysian residential development industry is severely plagued with a high level of bureaucracy, a multiplicity of approving agencies and tight planning legislations. These are the main impediments to a responsive housing delivery system. In addition, research findings indicate inherent tensions in the interaction between developers and the state which is caused by the weak influence of developers in shaping government policy. There was evidence of an informal culture, particularly extensive relationship building between developers and the state and in their application for planning permission. In some extreme cases, there was some evidence of malpractice. The state, professionals and homebuyers are found to be in tension and conflict with developers. Developers are seen to be extremely profit-driven to the extent of flouting the regulations which they claim to be excessive and outmoded. The Malaysian residential industry has weak institutional capacity as it is characterised by a lack of trust and suspicion between developers and the state, and between developers and professionals. Hence, this thesis attempts to address the hindrances to effective implementation of legislative frameworks and to propose ways to overcome the present weaknesses. It also identifies some future directions for similar research to be carried out in Malaysia.
- Published
- 2010
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