Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

The core role of the nurse practitioner: practice, professionalism and clinical leadership.

AIM: To draw on empirical evidence to illustrate the core role of nurse practitioners in Australia and New Zealand. BACKGROUND: Enacted legislation provides for mutual recognition of qualifications, including nursing, between New Zealand and Australia. As the nurse practitioner role is relatively new in both countries, there is no consistency in role expectation and hence mutual recognition has not yet been applied to nurse practitioners. A study jointly commissioned by both countries' Regulatory Boards developed information on the core role of the nurse practitioner, to develop shared competency and educational standards. Reporting on this study's process and outcomes provides insights that are relevant both locally and internationally. METHOD: This interpretive study used multiple data sources, including published and grey literature, policy documents, nurse practitioner program curricula and interviews with 15 nurse practitioners from the two countries. Data were analysed according to the appropriate standard for each data type and included both deductive and inductive methods. The data were aggregated thematically according to patterns within and across the interview and material data. FINDINGS: The core role of the nurse practitioner was identified as having three components: dynamic practice, professional efficacy and clinical leadership. Nurse practitioner practice is dynamic and involves the application of high level clinical knowledge and skills in a wide range of contexts. The nurse practitioner demonstrates professional efficacy, enhanced by an extended range of autonomy that includes legislated privileges. The nurse practitioner is a clinical leader with a readiness and an obligation to advocate for their client base and their profession at the systems level of health care. CONCLUSION: A clearly articulated and research informed description of the core role of the nurse practitioner provides the basis for development of educational and practice competency standards. These research findings provide new perspectives to inform the international debate about this extended level of nursing practice. RELEVANCE TO CLINICAL PRACTICE: The findings from this research have the potential to achieve a standardised approach and internationally consistent nomenclature for the nurse practitioner role.

The role of the rule of law in virtual communities

There is a severe tendency in cyberlaw theory to delegitimize state intervention in the governance of virtual communities. Much of the existing theory makes one of two fundamental flawed assumptions: that communities will always be best governed without the intervention of the state; or that the territorial state can best encourage the development of communities by creating enforceable property rights and allowing the market to resolve any disputes. These assumptions do not ascribe sufficient weight to the value-laden support that the territorial state always provides to private governance regimes, the inefficiencies that will tend to limit the development utopian communities, and the continued role of the territorial state in limiting autonomy in accordance with communal values. In order to overcome these deterministic assumptions, this article provides a framework based upon the values of the rule of law through which to conceptualise the legitimacy of the private exercise of power in virtual communities. The rule of law provides a constitutional discourse that assists in considering appropriate limits on the exercise of private power. I argue that the private contractual framework that is used to govern relations in virtual communities ought to be informed by the values of the rule of law in order to more appropriately address the governance tensions that permeate these spaces. These values suggest three main limits to the exercise of private power: that governance is limited by community rules and that the scope of autonomy is limited by the substantive values of the territorial state; that private contractual rules should be general, equal, and certain; and that, most importantly, internal norms be predicated upon the consent of participants.

Vectors and alternative hosts of tobacco yellow dwarf virus in southeastern Australia

Factors that determine the epidemiology of Tobacco yellow dwarf virus (TbYDV), including alternative host plants and insect vector(s), were assessed over three consecutive growing seasons at four field sites in Northeastern Victoria in commercial tobacco growing properties. In addition, these factors were assessed for one growing season at three bean growing properties. Overall, 23 leafhopper species were identified at the 7 sites, with Orosius orientalis as the predominant leafhopper. Of the leafhoppers collected, only O. orientalis and Anzygina zealandica tested positive for TbYDV by polymerase chain reaction (PCR). The population dynamics of O. orientalis was assessed using sweep net sampling over three growing seasons and a trimodal distribution was observed. Despite large numbers of O. orientalis occurring early in the growing season (September–October), TbYDV was only detected in these leafhoppers between late November and end of January. The peaks in the detection of TbYDV in O. orientalis correlated with the observation of disease symptoms in tobacco and bean and were associated with warmer temperatures and lower rainfall. Spatial and temporal distribution of vegetation at selected sites was determined using quadrat sampling. Of the 40 plant species identified, TbYDV was detected only in four dicotyledonous species, Amaranthus retroflexus, Phaseolus vulgaris, Nicotiana tabacum and Raphanus raphanistrum. The proportion of host and non-host availability for leafhoppers was associated with climatic conditions.

Molecular characterisation of six badnavirus species associated with leaf streak disease of banana in East Africa

Banana leaf streak disease, caused by several species of Banana streak virus (BSV), is widespread in East Africa. We surveyed for this disease in Uganda and Kenya, and used rolling-circle amplification (RCA) to detect the presence of BSV in banana. Six distinct badnavirus sequences, three from Uganda and three from Kenya, were amplified for which only partial sequences were previously available. The complete genomes were sequenced and characterised. The size and organisation of all six sequences was characteristic of other badnaviruses, including conserved functional domains present in the putative polyprotein encoded by open reading frame (ORF) 3. Based on nucleotide sequence analysis within the reverse transcriptase/ribonuclease H-coding region of open reading frame 3, we propose that these sequences be recognised as six new species and be designated as Banana streak UA virus, Banana streak UI virus, Banana streak UL virus, Banana streak UM virus, Banana streak CA virus and Banana streak IM virus. Using PCR and species-specific primers to test for the presence of integrated sequences, we demonstrated that sequences with high similarity to BSIMV only were present in several banana cultivars which had tested negative for episomal BSV sequences.

The ecology of Bactrocera tryoni (Froggatt) (Diptera: Tephritdae) : what do we know to assist pest management?

The distribution, systematics and ecology of Bactrocera tryoni, the Queensland fruit fly are reviewed. Bactrocera tryoni is a member of the B. tryoni complex of species, which currently includes four named species, viz. B. tryoni s.s., B. neohumeralis, B. melas and B. aquilonis. The species status of B. melas and B. aquilonis are unclear (they may be junior synonyms of B. tryoni) and their validity, or otherwise, needs to be confirmed as a matter of urgency. While Queensland fruit fly is regarded as a tropical species, it cannot be assumed that its distribution will spread further south under climate change scenarios. Increasing aridity and hot dry summers, as well as more complex, indirect interactions resulting from elevated CO2, make predicting the future distribution and abundance of B. tryoni difficult. The ecology of B. tryoni is reviewed with respect to current control approaches (with the exception of Sterile Insect Technique which is covered in a companion paper). We conclude that there are major gaps in the knowledge required to implement most non-insecticide based management approaches. Priority areas for future research include host plant interactions, protein and cue-lure foraging and use, spatial dynamics, development of new monitoring tools, investigating the use of natural enemies and better integration of fruit flies into general horticultural IPM systems.

Cultivar-specific effects of pathogen testing on storage root yield of sweet potato, Ipomoea batatas (L.) Lam.

The accumulation and perpetuation of viral pathogens over generations of clonal propagation in crop species such as sweet potato, Ipomoea batatas,inevitably result in a reduction in crop yield and quality. This study was conducted at Bundaberg, Australia to compare the productivity of field-derived and pathogen-tested (PT)clones of 14 sweet potato cultivars and the yield benefits of using healthy planting materials. The field-derived clonal materials were exposed to the endemic viruses, while the PT clones were subjected to thermotherapy and meristem-tip culture to eliminate viral pathogens. The plants were indexed for viruses using nitrocellulose membrane-enzyme-linked immunosorbent assay and graft-inoculations onto Ipomoea setosa. A net benefit of 38% in storage root yield was realised from using PT materials in this study.Conversely, in a similar study previously conducted at Kerevat, Papua New Guinea (PNG), a net deficit of 36% was realised. This reinforced our finding that the response to pathogen testing was cultivar dependent and that the PNG cultivars in these studies generally exhibited increased tolerance to the endemic viruses present at the respective trial sites as manifested in their lack of response from the use of PT clones. They may be useful sources for future resistance breeding efforts. Nonetheless, the potential economic gain from using PT stocks necessitates the use of pathogen testing on virus-susceptible commercial cultivars.

A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

A method for evaluating lean assembly process at design stage

Lean product design has the potential to reduce the overall product development time and cost and can improve the quality of a product. However, it has been found that no or little work has been carried out to provide an integrated framework of "lean design" and to quantitatively evaluate the effectiveness of lean practices/principles in product development process. This research proposed an integrated framework for lean design process and developed a dynamic decision making tool based on Methods Time Measurement (MTM) approach for assessing the impact of lean design on the assembly process. The proposed integrated lean framework demonstrates the lean processes to be followed in the product design and assembly process in order to achieve overall leanness. The decision tool consists of a central database, the lean design guidelines, and MTM analysis. Microsoft Access and C# are utilized to develop the user interface to use the MTM analysis as decision making tool. MTM based dynamic tool is capable of estimating the assembly time, costs of parts and labour of various alternatives of a design and hence is able to achieve optimum design. A case study is conducted to test and validate the functionality of the MTM Analysis as well as to verify the lean guidelines proposed for product development.