Nuclear receptor and nuclear receptor target gene messenger ribonucleic acid levels at different sites of the gastrointestinal tract and in liver of healthy dogs

Nuclear receptors (NR) are ligand-activated transcription factors that regulate different metabolic pathways by influencing the expression of target genes. The current study examined mRNA abundance of NR and NR target genes at different sites of the gastrointestinal tract (GIT) and the liver of healthy dogs (Beagles; n = 11). Samples of GIT and liver were collected postmortem and homogenized, total RNA was extracted and reverse transcribed, and gene expression was quantified by real-time reverse-transcription PCR relative to the mean of 3 housekeeping genes (beta-actin, glyceraldehyde-3-phosphate dehydrogenase, and ubi-quitin). Differences were observed (P < or = 0.05) in the mRNA abundance among stomach (St), duodenum (Du), jejunum (Je), ileum (Il), and colon (Col) for NR [pregnane X receptor (Du, Je > Il, Col > St), peroxisome proliferator-associated receptor gamma (St, Du, Col > Je, Il), constitutive androstane receptor (Je, Du > Il, Col), and retinoid x receptor alpha (Du > Il)] and NR target genes [glutathione-S-transferase A3-3 (Du > Je > St, Il; St > Col), phenol-sulfating phenol sulfotransferase 1A1 (Du, Je > Il, St; Col > St), cytochrome P450 3A12 (Du, Je > St, Il, Col), multiple drug resistance gene 1 (Du, Je, Il, Col > St), multiple drug resistance-associated protein 2 (Je, Du > Il > St, Col), multiple drug resistance-associated protein 3 (Col > St > Il; Du > Je, Il; St > Il), NR corepressor 2 (St > Il, Col), and cytochrome P450 reductase (St, Du, Je > Il, Col)], but not for peroxisome proliferator-associated receptor alpha. Differences (P > 0.05) in mRNA abundance in the liver relative to the GIT were also observed. In conclusion, the presence of numerous differences in expression of NR and NR target genes in different parts of the GIT and in liver of healthy dogs may be associated with location-specific functions and regulation of GIT regions.

Effects of dexamethasone on mRNA abundance of nuclear receptors and hepatic nuclear receptor target genes in neonatal calves

Hepatic nuclear receptors (NR), particularly constitutive androstane receptor (CAR) and pregnane X receptor (PXR), are involved in the coordinated transcriptional control of genes that encode proteins involved in the metabolism and detoxification of xeno- and endobiotics. A broad spectrum of metabolic processes are mediated by NR acting in concert with ligands such as glucocorticoids. This study examined the role of dexamethasone on hepatic mRNA expression of CAR, PXR and several NR target genes. Twenty-eight male calves were allotted to one of four treatment groups in a 2 x 2 arrangement of treatments: feed source (colostrum or milk-based formula) and glucocorticoid administration (twice daily intramuscular dexamethasone). Liver biopsies were obtained at 5 days of age. Real-time reverse transcription polymerase chain reaction was used to quantify mRNA abundances. No effects of feed source on mRNA abundances were observed. For the NR examined, mRNA abundance of both CAR and PXR in dexamethasone-treated calves was lower (p < 0.05) by 39% and 40%, respectively, than in control calves. Abundance of NR target genes exhibited a mixed response. SULT1A1 mRNA abundance was 39% higher (p < 0.05) in dexamethasone-treated calves compared with control calves. mRNA abundance of CYP2C8 tended also to be higher (+44%; p = 0.053) after dexamethasone treatment. No significant treatment effects (p > 0.10) were observed for mRNA abundances of CYP3A4, CYP2E1, SULT2A1, UGT1A1 or cytochrome P450 reductase (CPR). In conclusion, an enhanced glucocorticoid status, induced by pharmacological amounts of dexamethasone, had differential and in part unexpected effects on NR and NR target systems in 5-day-old calves. Part of the unexpected responses may be due the immaturity of NR and NR receptor target systems.

Probabilistic-based hurricane risk assessment and mitigation considering the potential impacts of climate change

Studies are suggesting that hurricane hazard patterns (e.g. intensity and frequency) may change as a consequence of the changing global climate. As hurricane patterns change, it can be expected that hurricane damage risks and costs may change as a result. This indicates the necessity to develop hurricane risk assessment models that are capable of accounting for changing hurricane hazard patterns, and develop hurricane mitigation and climatic adaptation strategies. This thesis proposes a comprehensive hurricane risk assessment and mitigation strategies that account for a changing global climate and that has the ability of being adapted to various types of infrastructure including residential buildings and power distribution poles. The framework includes hurricane wind field models, hurricane surge height models and hurricane vulnerability models to estimate damage risks due to hurricane wind speed, hurricane frequency, and hurricane-induced storm surge and accounts for the timedependant properties of these parameters as a result of climate change. The research then implements median insured house values, discount rates, housing inventory, etc. to estimate hurricane damage costs to residential construction. The framework was also adapted to timber distribution poles to assess the impacts climate change may have on timber distribution pole failure. This research finds that climate change may have a significant impact on the hurricane damage risks and damage costs of residential construction and timber distribution poles. In an effort to reduce damage costs, this research develops mitigation/adaptation strategies for residential construction and timber distribution poles. The costeffectiveness of these adaptation/mitigation strategies are evaluated through the use of a Life-Cycle Cost (LCC) analysis. In addition, a scenario-based analysis of mitigation strategies for timber distribution poles is included. For both residential construction and timber distribution poles, adaptation/mitigation measures were found to reduce damage costs. Finally, the research develops the Coastal Community Social Vulnerability Index (CCSVI) to include the social vulnerability of a region to hurricane hazards within this hurricane risk assessment. This index quantifies the social vulnerability of a region, by combining various social characteristics of a region with time-dependant parameters of hurricanes (i.e. hurricane wind and hurricane-induced storm surge). Climate change was found to have an impact on the CCSVI (i.e. climate change may have an impact on the social vulnerability of hurricane-prone regions).

Between Equity and Empathy: Social Professions and the New Accountability

This article explores the practical and ethical implications of the ‘new accountability’ (working to procedures, targets and standards) based on interviews with British social professionals. Although similar tendencies are present in other European countries, in Britain the rule-bound nature of social work is more intense. Practitioners who regard the ‘new accountability’ positively justify their views with reference to utilitarian and rights-based arguments relating to the promotion of good outcomes, the achievement of equity, respecting the consumer rights of service users and the rights of other stakeholders to information and value for money. Those practitioners who view the new accountability requirements negatively seem to speak in a different ‘moral voice’, which can be linked to more personal and situated approaches to ethics, stressing the importance of particular relationships in context, trust, sensitivity and a sense of ‘vocation’. Both ‘voices’ are part of professional practice, but the new accountability stresses the former at the expense of the latter. For social work to play the critical role identified by Walter Lorenz, maintaining a creative balance between equity and empathy will be important.

Policy Contexts of Social Work in Britain: the wider implications of 'New' Labour and the 'New Legal Regime'

Several commentators have expressed disappointment with New Labour's apparent adherence to the policy frameworks of the previous Conservative administrations. The employment orientation of its welfare programmes, the contradictory nature of the social exclusion initiatives, and the continuing obsession with public sector marketisation, inspections, audits, standards and so on, have all come under critical scrutiny (c.f., Blyth 2001; Jordan 2001; Orme 2001). This paper suggests that in order to understand the socio-economic and political contexts affecting social work we need to examine the relationship between New Labour's modernisation project and its insertion within an architecture of global governance. In particular, membership of the European Union (EU), International Monetary Fund (IMF) and World Trade Organisation (WTO) set the parameters for domestic policy in important ways. Whilst much has been written about the economic dimensions of 'globalisation' in relation to social work rather less has been noted about the ways in which domestic policy agenda are driven by multilateral governance objectives. This policy dimension is important in trying to respond to various changes affecting social work as a professional activity. What is possible, what is encouraged, how things might be done, is tightly bounded by the policy frameworks governing practice and affected by those governing the lives of service users. It is unhelpful to see policy formulation in purely national terms as the UK is inserted into a network governance structure, a regulatory framework where decisions are made by many countries and organisations and agencies. Together, they are producing a 'new legal regime', characterised by a marked neo-liberal policy agenda. This paper aims to demonstrate the relationship of New Labour's modernisation programme to these new forms of legality by examining two main policy areas and the welfare implications they are enmeshed in. The first is privatisation, and the second is social policy in the European Union. Examining these areas allows a demonstration of how much of the New Labour programme can be understood as a local implementation of a transnational strategy, how parts of that strategy produce much of the social exclusion it purports to address, and how social welfare, and particularly social work, are noticeable by their absence within policy discourses of the strategy. The paper details how the privatisation programme is considered to be a crucial vehicle for the further development of a transnational political-economy, where capital accumulation has been redefined as 'welfare'. In this development, frameworks, codes and standards are central, and the final section of the paper examines how the modernisation strategy of the European Union depends upon social policy marked by an employment orientation and risk rationality, aimed at reconfiguring citizen identities.The strategy is governed through an 'open mode of coordination', in which codes, standards, benchmarks and so on play an important role. The paper considers the modernisation strategy and new legality within which it is embedded as dependent upon social policy as a technology of liberal governance, one demonstrating a new rationality in comparison to that governing post-Second World War welfare, and which aims to reconfigure institutional infrastructure and citizen identity.

Social Work and a New Social Order - Challenging Neo-liberalism's Erosion of Solidarity

The world in which social work operates today is a very different world from that in which most of us took their social work training, and the changes we are facing are profound. This paper argues that these changes are not merely a regime change in social policy but that they are essentially about a re-ordering of social relationships and attempt to model them on neo-liberal ideas. In view of these pressures it is understandable that social workers often try to ignore those changes and withdraw into a private world of therapeutic relationships in which the methods they trained in are made to be still valid, or they simply go along with new service delivery designs without asking too many questions. Both reactions fail to question what the "social" can still mean in the light of these changes and how social workers can fulfil their mandate to be responsible for the social dimension of public life. Nothing less than a head-on challenge of the basic presuppositions of neo-liberalism (Willke 2003) and their manifold applications to social service delivery systems will thereby suffice.