Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone.

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of alpha-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and alpha-MSH production in RAW 264.7 cultured murine macrophages stimulated with bacterial lipopolysaccharide and interferon gamma. alpha-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. alpha-MSH increased cAMP accumulation in RAW cells, characteristic of alpha-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary alpha-MSH receptor (melanocortin 1). mRNA for proopiomelanocortin, the precursor molecular of alpha-MSH, was expressed in RAW cells, and tumor necrosis factor alpha increased production and release of alpha-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor alpha can induce macrophages to increase production of alpha-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of NO. The results suggest that alpha-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.

Identification of the local productive systems in Spain: a new approach

Paper submitted to the 44th European Congress of the European Regional Science Association, Porto, 25-29 August 2004.

Cultural Politics of Resilience in Kingston, Jamaica

Recently, resilience has become a catchall solution for some of the world’s most pressing ecological, economic and social problems. This dissertation analyzes the cultural politics of resilience in Kingston, Jamaica by examining them through their purported universal principles of adaptation and flexibility. On the one hand, mainstream development regimes conceptualize resilience as a necessary and positive attribute of economies, societies and cultures if we are to survive any number of disasters or disturbances. Therefore, in Jamaican cultural and development policy resilience is championed as both a means and an end of development. On the other hand, critics of resilience see the new rollout of resilience projects as deepening neoliberalism, capitalism and new forms of governmentality because resilience projects provide the terrain for new forms of securitization and surveillance practices. These scholars argue that resilience often forecloses the possibilities to resist that which threatens us. However, rather than dismissing resilience as solely a sign of domination and governmentality, this dissertation argues that resilience must be understood as much more ambiguous and complex, rather than within binaries such as subversion vs. neoliberal and resistance vs. resilience. Overly simplistic dualities of this nature have been the dominant approach in the scholarship thus far. This dissertation provides a close analysis of resilience in both multilateral and Jamaican government policy documents, while exploring the historical and contemporary production of resilience in the lives of marginalized populations. Through three sites within Kingston, Jamaica—namely dancehall and street dances, WMW-Jamaica and the activist platform SO((U))L HQ—this dissertation demonstrates that “resilience” is best understood as an ambiguous site of power negotiations, social reproduction and survival in Jamaica today. It is often precisely this ambiguous power of ordinary resilience that is capitalized on and exploited to the detriment of vulnerable groups. At once demonstrating creative negotiation and reproduction of colonial capitalist social relations within the realms of NGO, activist work and cultural production, this dissertation demonstrates the complexity of resilience. Ultimately, this dissertation draws attention to the importance of studying spaces of cultural production in order to understand the power and limits of contemporary policy discourses and political economy. 

Growth, viral production and metabolism of a Helicoverpa zea cell line in serum-free culture

Insect cell cultures have been extensively utilised for means of production for heterologous proteins and biopesticides. Spodoptera frugiperda (Sf9) and Trichoplusia ni (High Five(TM)) cell lines have been widely used for the production of recombinant proteins, thus metabolism of these cell lines have been investigated thoroughly over recent years. The Helicoverpa zea cell line has potential use for the production of a biopesticide, specifically the Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus (HaSNPV). The growth, virus production, nutrient consumption and waste production of this cell line was investigated under serum-free culture conditions, using SF900II and a low cost medium prototype (LCM). The cell growth ( growth rates and population doubling time) was comparable in SF900II and LCM, however, lower biomass and cell specific virus yields were obtained in LCM. H. zea cells showed a preference for asparagine over glutamine, similar to the High Five(TM) cells. Ammonia was accumulated to significantly high levels (16 mM) in SF900II, which is an asparagine and glutamine rich medium. However, given the absence of asparagine and glutamine in the medium ( LCM), H. zea cells adapted and grew well in the absence of these substrates and no accumulation of ammonia was observed. The adverse effect of ammonia on H. zea cells is unknown since good production of biologically active HaSNPV was achieved in the presence of high ammonia levels. H. zea cells showed a preference for maltose even given an abundance supply of free glucose. Accumulation of lactate was observed in H. zea cell cultures.

The incidence and intensity of employer funded training: Australian evidence on the impact of flexible work

The interaction between the growth of flexible forms of employment and employer funded training is important for understanding labour market performance. In particular, the idea of a trade-off has been advanced to describe potential market failures in the employment of flexible workers. This study finds that evidence of a trade-off is apparent in both the incidence and intensity of employer funded training. Flexible workers receive training that is 50-80% less intense than the workforce average. Casual workers - especially males - suffer more acutely from the trade-off. This suggests that flexible production externalities may seriously reduce human capital formation in the workforce.

The Evolving Nature of Small-Scale Forestry in Australia

Two forms of small-scale forestry are developing in Australia, each with different impacts on rural communities. One is based on growing short-rotation Eucalyptus globulus (blue gum) for pulp and the other on production of higher-value products from longer-rotation native hard-woods. Several impediments exist to further development of small-scale forestry, including the lack of a small-scale forestry culture, concerns over harvest rights, lack of market development, the long wait for returns, and satisfaction with current land uses. Nevertheless, the rapid increase in farm woodlot establishment in the past five years has paralleled the strong increase in the private industrial plantation estate. As markets develop and hindrances are overcome, landholders not previously interested in small-scale forestry may consider ita worthwhile land use.

Stable production of hyaluronic acid in Streptococcus zooppidemicus chemostats operated at high dilution rate

Hyaluronic acid is routinely produced through fermentation of both Group A and C streptococci. Despite significant production costs associated with short fermentations and removal of contaminating proteins released during entry into stationary phase, hyaluronic acid is typically produced in batch rather than continuous culture. The main reason is that hyaluronic acid synthesis has been found to be unstable in continuous culture except at very low dilution rates. Here, we investigated the mechanisms underlying this instability and developed a stable, high dilution rate (0.4 h(-1)) chemostat process for both chemically defined and complex media operating for more than 150 h of production. In chemically defined medium, the product yield was 25% higher in chemostat cultures than in conventional batch culture when arginine or glucose was the limiting substrate. In contrast, glutamine limitation resulted in higher ATP requirements and a yield similar to that observed in batch culture. In complex, glucose-limited medium, ATP requirements were greatly reduced but biomass synthesis was favored over hyaluronic acid and no improvement in hyaluronic acid yield was observed. The successful establishment of continuous culture at high dilution rate enables both commercial production at reduced cost and a more rational characterization and optimization of hyaluronic acid production in streptococci. (c) 2005 Wiley Periodicals, Inc.

Survival strategy of Echinococcus multilocularis in the human host

As exemplified by aborted calcified liver lesions commonly found in patients from endemic areas, Echinococcus multilocularis metacestodes develop only in a minority of individuals exposed to infection with the papasite. Clinical research has disclosed some aspects of the survival strategy of E. multilocularis in human hosts. Clinical observations in liver transplantation and AIDS suggest that suppression of cellular/Th1related immunity increases disease severity. Most of the studies have stressed a role for CD8+ T cells and for Interleukin-10 in the development of tolerance. A spontaneous secretion of IL-10 by the PBMC seems to be the immunological hallmark of patients with progressive forms of alveolar echinococcosis (AE). IL-10-induced inhibition of effector macrophages, but also of antigen-presenting dendritic cells, may be operating and allowing parasite growth and survival. The genetic correlates of susceptibility to infection with E. multilocularis are clearer in humans than in the mouse model. A significant link between MHC polymorphism and clinical presentation of AE has been shown, and the spontaneous secretion of IL-10 in patients with a progressive AE is higher in patients with the HLA DR3+, DQ2+ haplotype. Clustering of cases in certain families, in communities otherwise exposed to similar risk factors, also points to immuno-genetic predisposition factors that may allow the larva to escape host immunity more easily. The first stage of larval development may be crucial in producing danger signals stimulating the initial production of cytokines. Therapeutic use of Interferon alpha is an attempt to foil the survival strategy of E. multilocularis. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

The role of carbon in fuel cells

Carbon possesses unique electrical and structural properties that make it an ideal material for use in fuel cell construction. In alkaline, phosphoric acid and proton-exchange membrane fuel cells (PEMFCs), carbon is used in fabricating the bipolar plate and the gas-diffusion layer. It can also act as a support for the active metal in the catalyst layer. Various forms of carbon - from graphite and carbon blacks to composite materials - have been chosen for fuel-cell components. The development of carbon nanotubes and the emergence of nanotechnology in recent years has therefore opened up new avenues of matenials development for the low-temperature fuel cells, particularly the hydrogen PEMFC and the direct methanol PEMFC. Carbon nanotubes and aerogels are also being investigated for use as catalyst support, and this could lead to the production of more stable, high activity catalysts, with low platinum loadings (< 0.1 Mg cm(-2)) and therefore low cost. Carbon can also be used as a fuel in high-temperature fuel cells based on solid oxide, alkaline or molten carbonate technology. In the direct carbon fuel cell (DCFC), the energy of combustion of carbon is converted to electrical power with a thermodynamic efficiency close to 100%. The DCFC could therefore help to extend the use of fossil fuels for power generation as society moves towards a more sustainable energy future. (c) 2006 Elsevier B.V. All rights reserved.

Extent and economic effect of heat loads on dairy cattle production in Australia

Objective To investigate the extent of heat load problems, caused by the combination of excessive temperature and humidity, in Holstein-Friesian cows in Australia. Also, to outline how milk production losses and consequent costs from this can be estimated and minimised. Procedures Long-term meteorological data for Australia were analysed to determine the distribution of hot conditions over space and time. Fifteen dairy production regions were identified for higher-resolution data analysis. Both the raw meteorological data and their integration into a temperature-humidity thermal index were compiled onto a computer program. This mapping software displays the distribution of climatic patterns, both Australia-wide and within the selected dairying regions. Graphical displays of the variation in historical records for 200 locations in the 15 dairying regions are also available. As a separate study, production data from research stations, on-farm trials and milk factory records were statistically analysed and correlated with the climatic indices, to estimate production losses due to hot conditions. Results Both milk yields and milk constituents declined with increases in the temperature-humidity index. The onset and rate of this decline are dependent on a number of factors, including location, level of production, adaptation, and management regime. These results have been integrated into a farm-level economic analysis for managers of dairy properties. Conclusion By considering the historical patterns of hot conditions over time and space, along with expected production losses, managers of dairy farms can now conduct an economic evaluation of investment strategies to alleviate heat loads. These strategies include the provision of sprinklers, shade structures, or combinations of these.

Applying a Systems Approach to the Analysis of the Benefits of Conversion to Organic Production

Although the current level of organic production in industrialised countries amounts to little more than 1-2 percent, it is recognised that one of the major issues shaping agricultural output over the next several decades will be the demand for organic produce (Dixon et al. 2001). In Australia, the issues of healthy food and environmental concern contribute to increasing demand and market volumes for organic produce. However, in Indonesia, using more economical inputs for organic production is a supply-side factor driving organic production. For individual growers and processors, conversion from conventional to organic agriculture is often a challenging step, entailing a thorough revision of established practices and heightened market insecurity. This paper examines the potential for a systems approach to the analysis of the conversion process, to yield insights for household and community decisions. A framework for applying farming systems research to investigate the benefits of organic production in both Australia and Indonesia is discussed. The framework incorporates scope for farmer participation, crucial to the understanding of farming systems; analysis of production; and relationships to resources, technologies, markets, services, policies and institutions in their local cultural context. A systems approach offers the potential to internalise the external effects that may be constraining decisions to convert to organic production, and for the design of decision-making tools to assist households and the community. Systems models can guide policy design and serve as a mechanism for predicting the impact of changes to the policy and market environments. The increasing emphasis of farming systems research on community and environment in recent years is in keeping with the proposed application to organic production, processing and marketing issues. The approach will also facilitate the analysis of critical aspects of the Australian production, marketing and policy environment, and the investigation of these same features in an Indonesian context.

The return of the Prince of Denmark: a survey on recent developments in the economics of innovation

It is well known that innovation is the engine that drives the growth machine of modern capitalist economies. Therefore, not surprisingly, substantial attention has been devoted by economists to the process behind the production of innovations. Three areas have recently emerged as relevant in the field. These are: the impact of spillovers on productivity; the different forms of R&D cooperation and the role of patents in fostering innovations when these are cumulative. In this paper I summarise the relevant literature in these three areas by discussing where the current literature stands and what are its future developments.

Fatty acid derivatised analogues of glucose-dependent insulinotropic polypeptide with improved antihyperglycaemic and insulinotropic properties

C-terminal acylation of Lys(37) with myristic (MYR; tetradecanoic acid), palmitic (PAL; hexadecanoic acid) and stearic (octadecanoic acid) fatty acids with or without N-terminal acetylation was employed to develop long-acting analogues of the glucoregulatory hormone, glucose-dependent insulinotropic polypeptide (GIP). All GIP analogues exhibited resistance to dipeptidylpeptidase-IV (DPP-IV) and significantly improved in vitro cAMP production and insulin secretion. Administration of GIP analogues to ob/ob mice significantly lowered plasma glucose-GIP(Lys(37)MYR), N-AcGIP(Lys(37)MYR) and GIP(Lys(37)PAL) increased plasma insulin concentrations. GIP(Lys(37)MYR) and N-AcGIP(Lys(37)MYR) elicited protracted glucose-lowering effects when administered 24h prior to an intraperitoneal glucose load. Daily administration of GIP(Lys(37)MYR) and N-AcGIP(Lys(37)MYR) to ob/ob mice for 24 days decreased glucose and significantly improved plasma insulin, glucose tolerance and beta-cell glucose responsiveness. Insulin sensitivity, pancreatic insulin content and triglyceride levels were not changed. These data demonstrate that C-terminal acylation particularly with myristic acid provides a class of stable, longer-acting forms of GIP for further evaluation in diabetes therapy.

The role of expertise in governance processes

In present day knowledge societies political decisions are often justified on the basis of scientific expertise. Traditionally, a linear relation between knowledge production and application was postulated which would lead, with more and better science, to better policies. Empirical studies in Science and Technology studies have essentially demolished this idea. However, it is still powerful, not least among practitioners working in fields where decision making is based on large doses of expert knowledge. Based on conceptual work in the field of Science and Technology Studies (STS) I shall examine two cases of global environmental governance, ozone layer protection and global climate change. I will argue that hybridization and purification are important for two major forms of scientific expertise. One is delivered though scientific advocacy (by individual scientists or groups of scientists), the other through expert committees, i.e. institutionalized forms of collecting and communicating expertise to decision makers. Based on this analysis lessons will be drawn, also with regard to the stalling efforts at establishing an international forestry regime.

Aluminium and Alzheimer's disease: review of possible pathogenic mechanisms

Chronic exposure to aluminium (Al) remains a controversial possible cause of sporadic forms of Alzheimer's disease (AD). This article reviews the evidence that once Al enters the brain and individual brain cells, it may be involved in three pathological processes: (1) the production of abnormal forms of tau leading to the formation of cellular neurofibrillary tangles and neuropil threads; (2) the processing of the amyloid precursor protein, resulting in the formation of beta-amyloid deposits and senile plaques, and (3) that via the mutual histocompatibility system, Al could be involved in the initiation of the immune response observed in AD patients. Despite recent evidence that Al could be involved in these processes, a conclusive case that exposure to Al initiates the primary pathological process in sporadic AD remains to be established.