ROLE OF CAVEOLIN-3 IN THE MODULATION OF HERG POTASSIUM CHANNEL

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr) that is important for cardiac repolarization. Previously, we have discovered that hERG channels rapidly internalize in low extracellular K+ ([K+]o). In cell culture, this process is driven by the endocytic protein, caveolin-1 (Cav1), which is an integral player in the caveolae-dependant endocytosis pathway. However, in the heart, Caveolin-3 (Cav3) is, in fact, the predominant form in the myocyte, and thus may play a direct role in regulating hERG expression in the heart. Thus, I hypothesize that this reduction of hERG conductance in cardiac myocytes derives from the presence of Cav3, which is integral regulator of hERG homeostasis innately in the heart. To investigate the effect of Cav3 on hERG, I overexpressed Cav3 in human embryonic kidney 293 (HEK-293) cells stably expressing hERG channels. Cav3 overexpression significantly and specifically decreased both the hERG current amplitude and the mature channel expression in normal culture conditions. Co-immunoprecipitation analysis and confocal imaging demonstrated an association between hERG and Cav3 in HEK cells as well as rat and rabbit cardiomyocytes. Mechanistically, I discovered that Cav3 possesses a faster turnover rate compared to Cav1, and can enhance hERG degradation through up-regulating mature channel ubiquitination via the ubiquitin ligase, NEDD4-2. Knockdown of Cav3 in neonatal cardiac myocytes also enhanced hERG expression. My data indicate that Cav3 participates in hERG trafficking, and is an important regulator of hERG channel homeostasis in cardiac myocytes. This information provides a platform for future intervention of the hERG-induced type-2 long QT syndrome (LQTS).

Calling for resistance: The political economy of Indian and Canadian call centre industries

Call centres have in the last three decades come to define the interaction between corporations, governments, and other institutions and their respective customers, citizens, and members. From telemarketing to tele-health services, to credit card assistance, and even emergency response systems, call centres function as a nexus mediating technologically enabled labour practices with the commodification of services. Because of the ubiquitous nature of the call centre in post-industrial capitalism, the banality of these interactions often overshadows the nature of work and labour in this now-global sector. Advances in telecommunication technologies and the globalization of management practices designed to oversee and maintain standardized labour processes have made call centre work an international phenomenon. Simultaneously, these developments have dislocated assumptions about the geographic and spatial seat of work in what is defined here as the new international division of knowledge labour. The offshoring and outsourcing of call centre employment, part of the larger information technology and information technology enabled services sectors, has become a growing practice amongst governments and corporations in their attempts at controlling costs. Leading offshore destinations for call centre work, such as Canada and India, emerged as prominent locations for call centre work for these reasons. While incredible advances in technology have permitted the use of distant and “offshore” labour forces, the grander reshaping of an international political economy of communications has allowed for the acceleration of these processes. New and established labour unions have responded to these changes in the global regimes of work by seeking to organize call centre workers. These efforts have been assisted by a range of forces, not least of which is the condition of work itself, but also attempts by global union federations to build a bridge between international unionism and local organizing campaigns in the Global South and Global North. Through an examination of trade union interventions in the call centre industries located in Canada and India, this dissertation contributes to research on post-industrial employment by using political economy as a juncture between development studies, critical communications, and labour studies.

Upin & Ipin: Promoting malaysian culture values through animation

Malaysian children lately have been exposed or influenced heavily by digital media entertainment. The rise of such entertainment tends to drive them away from understanding and appreciating the values of Malaysian culture. Upin and Ipin animation has successfully promoted Malaysian folklore culture and has significantly portrayed the art of Malaysian values including Islamic values by providing the platform for harmonious relationship among different societies or groups or religious backgrounds. The focus of this research is to look into the usage of Malaysian culture iconic visual styles such as backgrounds, lifestyles, character archetypes and narrative (storytelling). Therefore, we hope that this research will benefit the younger generation by highlighting the meaning and importance of implicit Malaysian culture.

Challenge of culture, conscience, and contract to general practitioners' care of their own health: qualitative study

Objective: To explore general practitioners' perceptions of the effects of their profession and training on their attitudes to illness in themselves and colleagues. Design: Qualitative study using focus groups and indepth interviews. Setting: Primary care in Northern Ireland. Participants: 27 general practitioners, including six recently appointed principals and six who also practised occupational medicine part time. Main outcome measures: Participants' views about their own and colleagues' health. Results: Participants were concerned about the current level of illness within the profession. They described their need to portray a healthy image to both patients and colleagues. This hindered acknowledgement of personal illness and engaging in health screening. Embarrassment in adopting the role of a patient and concerns about confidentiality also influenced their reactions to personal illness. Doctors' attitudes can impede their access to appropriate health care for themselves, their families, and their colleagues. A sense of conscience towards patients and colleagues and the working arrangements of the practice were cited as reasons for working through illness and expecting colleagues to do likewise. Conclusions: General practitioners perceive that their professional position and training adversely influence their attitudes to illness in themselves and their colleagues. Organisational changes within general practice, including revalidation, must take account of barriers experienced by general practitioners in accessing health care. Medical education and culture should strive to promote appropriate self care among doctors.

“Islands” in Holocene forests: implications for forest openness, landscape clearance and “culture-steppe” species

Human activity has undoubtedly had a major impact on Holocene forested ecosystems, with the concurrent expansion of plants and animals associated with cleared landscapes and pasture, also known as 'culture-steppe'. However, this anthropogenic perspective may have underestimated the contribution of autogenic disturbance (e.g. wind-throw, fire), or a mixture of autogenic and anthropogenic processes, within early Holocene forests. Entomologists have long argued that the north European primary forest was probably similar in structure to pasture woodland. This idea has received support from the conservation biologist Frans Vera, who has recently strongly argued that the role of large herbivores in maintaining open forests in the primeval landscapes of Europe has been seriously underestimated. This paper reviews this debate from a fossil invertebrate perspective and looks at several early Holocene insect assemblages. Although wood taxa are indeed important during this period, species typical of open areas and grassland and dung beetles, usually associated with the dung of grazing animals, are persistent presences in many early woodland faunas. We also suggest that fire and other natural disturbance agents appear to have played an important ecological role in some of these forests, maintaining open areas and creating open vegetation islands within these systems. More work, however, is required to ascertain the role of grazing animals, but we conclude that fossil insects have a significant contribution to make to this debate. This evidence has fundamental implications in terms of how the palaeoecological record is interpreted, particularly by environmental archaeologists and palaeoecologists who may be more interested in identifying human-environment interactions rather than the ecological processes which may be preserved within palaeoecological records.