124 resultados para T-Lymphocytes, Regulatory -- immunology


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With increasing recognition of the international market in health professionals and the impact of globalism on regulation, the governance of the health workforce is moving towards greater public engagement and increased transparency. This book discusses the challenges posed by these processes, such as improved access to health services and how structures can be reformed so that good practice is upheld and quality of service and patient safety are ensured.

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Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor α (TNFα) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNFα is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 4 and SNAP-23. Many functions in immune cells are coordinated from lipid rafts in the plasmamembrane, and we investigated a possible role for lipid rafts in TNFα trafficking and secretion. TNFα surface delivery and secretion were found to be cholesterol- dependent. Upon macrophage activation, syntaxin 4 was recruited to cholesterol-dependent lipid rafts, whereas its regulatory protein, Munc18c, was excluded from the rafts. Syntaxin 4 in activated macrophages localized to discrete cholesterol-dependent puncta on the plasmamembrane, particularly on filopodia. Imaging the early stages of TNFα surface distribution revealed these puncta to be the initial points of TNFα delivery. During the early stages of phagocytosis, syntaxin 4 was recruited to the phagocytic cup in a cholesterol dependent manner. Insertion of VAMP3-positive recycling endosome membrane is required for efficient ingestion of a pathogen. Without this recruitment of syntaxin 4, it is not incorporated into the plasma membrane, and phagocytosis is greatly reduced. Thus, relocation of syntaxin 4 into lipid rafts in macrophages is a critical and rate-limiting step in initiating an effective immune response.

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Proteasomes can exist in several different molecular forms in mammalian cells. The core 20S proteasome, containing the proteolytic sites, binds regulatory complexes at the ends of its cylindrical structure. Together with two 19S ATPase regulatory complexes it forms the 26S proteasome, which is involved in ubiquitin-dependent proteolysis. The 20S proteasome can also bind 11S regulatory complexes (REG, PA28) which play a role in antigen processing, as do the three variable c-interferoninducible catalytic b-subunits (e.g. LMP7). In the present study, we have investigated the subcellular distribution of the different forms of proteasomes using subunit speci®c antibodies. Both 20S proteasomes and their 19S regulatory complexes are found in nuclear, cytosolic and microsomal preparations isolated from rat liver. LMP7 was enriched approximately two-fold compared with core a-type proteasome subunits in the microsomal preparations. 20S proteasomes were more abundant than 26S proteasomes, both in liver and cultured cell lines. Interestingly, some signi®cant differences were observed in the distribution of different subunits of the 19S regulatory complexes. S12, and to a lesser extent p45, were found to be relatively enriched in nuclear fractions from rat liver, and immuno¯uorescent labelling of cultured cells with anti-p45 antibodies showed stronger labelling in the nucleus than in the cytoplasm. The REG was found to be localized predominantly in the cytoplasm. Three- to six-fold increases in the level of REG were observed following cinterferon treatment of cultured cells but c-interferon had no obvious effect on its subcellular distribution. These results demonstrate that different regulatory complexes and subpopulations of proteasomes have different distributions within mammalian cells and, therefore, that the distribution is more complex than has been reported for yeast proteasomes.

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The Australian economy has been transformed by bold federal government initiatives over the last decade. The political rhetoric is that without these reforms, the Australian economy will falter and be uncompetitive in a global market place. Despite the electoral disquiet that rapid systemic change brings, both sides of politics have adopted the broad starting point that it is imperative that our economy be transformed or Australian living standards will dramatically plummet...

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This paper considers the debate about the relationship between globalization and media policy from the perspective provided by a current review of the Australian media classification scheme. Drawing upon the author’s recent experience in being ‘inside’ the policy process, as Lead Commissioner on the Australian National Classification Scheme Review, it is argued that theories of globalization – including theories of neoliberal globalization – fail to adequately capture the complexities of the reform process, particularly around the relationship between regulation and markets. The paper considers the pressure points for media content policies arising from media globalization, and the wider questions surrounding media content policies in an age of media convergence.

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A key part of corporate governance reforms in Australia, as represented by CLERP 9, addresses concerns over the audit function and the role of independent auditors in monitoring managers and providing useful information to stakeholders about the financial position of the company. In comparing the regulatory responses to auditor independence dilemmas, there have been claims that CLERP 9 is less ‘stringent’ than the reforms imposed by the Sarbanes Oxley Act in the US. This paper looks at three particular situations that have been the subject of recent reform to strengthen independence: the mandatory rotation of auditors, recruitment of former auditors as board members, and provision of non-audit services to clients. In each case, we compare the similarities and differences of the regulatory response between Australia and US, to distil the efficacy of the CLERP 9 approach.

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Purpose Managers generally have discretion in determining how components of earnings are presented in financial statements in distinguishing between ‘normal’ earnings and items classified as unusual, special, significant, exceptional or abnormal. Prior research has found that such intra-period classificatory choice is used as a form of earnings management. Prior to 2001, Australian accounting standards mandated that unusually large items of revenue and expense be classified as ‘abnormal items’ for financial reporting, but this classification was removed from accounting standards from 2001. This move by the regulators was partly in response to concerns that the abnormal classification was being used opportunistically to manage reported pre-abnormal earnings. This study extends the earnings management literature by examining the reporting of abnormal items for evidence of intra-period classificatory earnings management in the unique Australian setting. Design/methodology/approach This study investigates associations between reporting of abnormal items and incentives in the form of analyst following and the earnings benchmarks of analysts’ forecasts, earnings levels, and earnings changes, for a sample of Australian top-500 firms for the seven-year period from 1994 to 2000. Findings The findings suggest there are systematic differences between firms reporting abnormal items and those with no abnormal items. Results show evidence that, on average, firms shifted expense items from pre-abnormal earnings to bottom line net income through reclassification as abnormal losses. Originality/value These findings suggest that the standard setters were justified in removing the ‘abnormal’ classification from the accounting standard. However, it cannot be assumed that all firms acted opportunistically in the classification of items as abnormal. With the removal of the standardised classification of items outside normal operations as ‘abnormal’, firms lost the opportunity to use such disclosures as a signalling device, with the consequential effect of limiting the scope of effectively communicating information about the nature of items presented in financial reports.

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Self-regulation is often promoted as a coping strategy that may allow older drivers to drive safely for longer. Self-regulation depends upon drivers making an accurate assessment of their own ability and having a willingness to practice self-regulatory behaviors to compensate for changes in ability. The current study explored the relationship between older drivers’ cognitive ability, their driving confidence and their use of self-regulation. An additional study aim was to explore the relationship between these factors and older drivers’ interest in driving programs. Seventy Australian drivers aged 65 years and over completed a questionnaire about their driving and a brief screening measure of cognitive ability (an untimed Clock Drawing Test). While all participants reported high levels of confidence regarding their driving ability, and agreed that they would continue driving in the foreseeable future, a notable proportion performed poorly on the Clock Drawing Test. Compared to older drivers who successfully completed the Clock Drawing Test, those who failed the cognitive test were significantly less likely to report driving self-regulation, and showed significantly less interest in being involved in driving programs. Older drivers with declining cognitive abilities may not be self-regulating their driving. This group also appears to be unlikely to self-refer to driving programs.

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The paper reveals that regulatory failure, often chronic, has characterised the regulatory environments of charities across time and locale. The analysis of the primary literature identifies common issues and suggested remedies pertaining to the regulatory failures of charities. These issues may well be appropriate for consideration by the commission and participants given their persistence in various inquiries for nearly four centuries. Such inquiries also considered other issues not directly referred to in this paper, to also include them would exponentially increase the already unwieldy size of this paper.