Copper in mammals: mechanisms of homeostasis and pathophysiology

The ability of mammals to tightly regulate systemic copper levels is vital for
health as demonstrated by the severity of the genetic copper deficiency and copper toxicity disorders, Menkes disease and Wilson disease, respectively. Analysis of these genetic disorders has led to a substantial increase in the understanding of the role of copper in health and disease. The isolation of the genes involved in these diseases and use of yeast mutants with altered copper and iron homeostasis has revealed a range of molecular mechanisms governing copper homeostasis. These mechanisms include regulation of cellular copper uptake and efflux and involve the use of chaperones for safe intracellular copper distribution. Here we provide an overview of the physiological role of copper and the molecular mechanisms
regulating systemic and cellular copper levels in mammals. Furthermore, we discuss the pathophysiological mechanisms and consequences of copper deficiency/overload in relation to disease.

Degradation mechanisms of benzo[a]pyrene and its accumulated metabolites by biodegradation combined with chemical oxidation

A high degradation extent of benzo[a]pyrene (BaP) should not be considered as the sole desirable criterion for the bioremediation of BaP-contaminated soils because some of its accumulated metabolites still have severe health risks to human. Two main metabolites of BaP, benzo[a]pyrene-1,6-quinone (BP1,6-quinone) and 3-hydroxybenzo[a]pyrene (3-OHBP) were identified by high performance liquid chromatography (HPLC) with standards. This study was the first time that degradation of both BaP and the two metabolites was carried out by chemical oxidation and biodegradation. Three main phases during the whole degradation process were proposed.

Hydrogen peroxide–zinc (H₂O₂–Zn), the fungus – Aspergillus niger and the bacteria – Zoogloea sp. played an important role in the different phases. The degradation parameters of the system were also optimized, and the results showed that the effect of degradation was the best when fungus–bacteria combined with H₂O₂–Zn, the concentration range of BaP in the cultures was 30–120 mg/l, the initial pH of the cultures was 6.0. However, as co-metabolites, phenanthrene significant inhibited the degradation of BaP. This combined degradation system compared with the conventional method of degradation by domestic fungus only, enhanced the degradation extent of BaP by more than 20% on the 12 d. The highest accumulation of BP1,6-quinone and 3-OHBP were reduced by nearly 10% in the degradation experiments, which further proved that the combined degradation system was more effective as far as joint toxicity of BaP and its metabolites are concerned.

Housing price diffusion pattern of Australia's state capital cities

The ripple effect of house prices within metropolitan areas has recently been recognised by researchers. However, it is very difficult to formulate and measure this effect using conventional house price theories particularly in consideration of the spatial locations of cities. Based on econometrics principles of the cointegration test and the error correction model, this research develops an innovative approach to quantitatively examine the diffusion patterns of house prices in mega-cities of a country. Taking Australia's eight capital cities as an example, the proposed approach is validated in terms of an empirical study. The results show that a 1-1-2-4 diffusion pattern exists within these cities. Sydney is on the top tier with Melbourne in the second; Perth and Adelaide are in the third level and the other four cities lie on the bottom. This research may be applied to predict the regional housing market behavior in a country.

Mechanisms of vasodilation in the dorsal aorta of the elephant fish, Callorhinchus milii (Chimaeriformes: Holocephali)

This study investigated vasodilator mechanisms in the dorsal aorta of the elephant fish, Callorhinchus milii, using anatomical and physiological approaches. Nitric oxide synthase could only be located in the perivascular nerve fibres and not the endothelium of the dorsal aorta, using NADPH histochemistry and immunohistochemistry. In vitro organ bath experiments demonstrated that a NO/soluble guanylyl cyclase (GC) system appeared to be absent in the vascular smooth muscle, since the NO donors SNP (10⁻⁴ mol l⁻¹) and SIN^-1 (10⁻⁵ mol l⁻¹) were without effect. Nicotine (3 × 10⁻⁴ mol l⁻¹) mediated a vasodilation that was not affected by ODQ (10⁻⁵ mol l⁻¹), _l-NNA (10⁻⁴ mol l⁻¹), indomethacin (10⁻⁵ mol l⁻¹), or removal of the endothelium. In contrast, the voltage-gated sodium channel inhibitor, tetrodotoxin (10⁻⁵ mol l⁻¹), significantly decreased the dilation induced by nicotine, suggesting that it contained a neural component. Pre-incubation of the dorsal aorta with the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP_8–37 (10⁻⁶ mol l^−  1) also caused a significant decrease in the nicotine-induced dilation. We propose that nicotine is mediating a neurally-derived vasodilation in the dorsal aorta that is independent of NO, prostaglandins and the endothelium, and partly mediated by CGRP.

The resource-based view of strategy: application to the agricultural industry

IP a The paper examines the application of the Resource-Based View of strategy (RBV) to the Australian floral industry. Despite the RBV's successful application to research in a number of discipline areas and the formalisation of its relationship with Competitive Advantage (CA) 15 years ago, the empirical support for the benefit of the RBV and development of research constructs has been inadequate. This has been partly due to the difficulty of identifying and separating the contribution of resources. The RBV literature is now consistent in the criteria required of a resource for CA and identifies a range of empirical research objectives (e.g. the need for contextual constructs), data evaluation focuses (e.g. measuring the impact of management, process, regional and scale affects) and results objectives (such as identifying the causal structure of resources). Research was conducted in the Australian floral industry to produce supporting generalisable data and constructs for the RBV. This industry is well bounded with several strongly differentiating resources and operates in a global market environment, which is necessary for these research objectives. Six hypotheses were examined; (1) the use of resources as the input of the CA, (2) the impact of the development process on resources, (3) the impact of management control on the development of resources (4) the impact on capability of management, process, region and scale, (5) the impact of resource development maturity on the approach to resource development and (6) the possibility of evaluating individual resources according to various criteria. The data was collected using selected participant interviews, with validation of conclusions by industry experts. It was analysed using content analysis, comparative analysis and cognitive mapping. The research determined that organisations in the Australian floral industry possessed important resources including geography, skills, technology, R&D, supply chains and production costs. These contributed to four CA creating production outputs; quality, capacity, reliability and customer convenience. The research findings supported hypotheses 1, 3, 4, 5 and 6. The lack of support for the two remaining hypotheses, relating to the process of resource development, may be explained by the low resource development maturity of the industry which masks the impact of the resource development process. The results also determined that one resource could contribute to a number of CAs and that resources not meeting all of the normal RBV CA criteria could still provide a CA in an industry where few resources met all criteria. It was postulated that these resources’ contribution to competitive was not durable.

Housing price diffusion pattern of Australia's state capital cities

The ripple effect of house prices within metropolitan areas has recently been recognised by researchers. However, it is very difficult to formulate and measure this effect using conventional house price theories particularly in consideration of the spatial locations of cities. Based on econometrics principles of the cointegration test and the error correction model, this research develops an innovative approach to quantitatively examine the diffusion patterns of house prices in mega-cities of a country. Taking Australia's eight capital cities as an example, the proposed approach is validated in terms of an empirical study. The results show that a 1-1-2-4 diffusion pattern exists within these cities. Sydney is on the top tier with Melbourne in the second; Perth and Adelaide are in the third level and the other four cities lie on the bottom. This research may be applied to predict the regional housing market behavior in a country.

Brief report : The defense mechanisms of homophobic adolescent males : a descriptive discriminant analysis

The study examined the role of defense mechanisms in homophobic attitudes of older male adolescents aged 17e18 years. A cross-sectional survey collected data from final year high school students (N ¼ 86) attending an all male school in a regional centre in Victoria, Australia. The school was identified by teachers as having a problematic culture of homophobic intolerance. Participants were divided into homophobic and non-homophobic groups based on their scores on the Homophobia Scale Questionnaire. Discriminant analysis was conducted to identify the predictors that would best categorise students into those two groups on the basis of defense styles derived from the Defense Style Questionnaire-40 (DSQ-40). The strongest predictors of homophobia amongst defense styles were idealisation, denial, somatisation and devaluation accounting for 18.31%, 17.64%, 13.10% and 11.35% of the variance, respectively. Results generally supported the larger contribution of more immature defenses to higher levels of homophobia.

Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells

We have developed hematopoietic cells resistant to the cytotoxic effects of oxysterols. Oxysterol-resistant HL60 cells were generated by continuous exposure to three different oxysterols—25-hydroxycholesterol (25-OHC), 7-beta-hydroxycholesterol (7β-OHC) and 7-keto-cholesterol (7κ-C). We investigated the effects of 25-OHC, 7β-OHC, 7κ-C and the apoptotic agent staurosporine on these cells. The effect of the calcium channel blocker nifedipine on oxysterol cytotoxicity was also investigated. Differential display and real-time PCR were used to quantitate gene expression of oxysterol-sensitive and -resistant cells. Our results demonstrate that resistance to the cytotoxic effects of oxysterols is relatively specific to the type of oxysterol, and that the cytotoxicity of 25-OHC but not that of 7β-OHC and 7κ-C, appears to occur by a calcium dependent mechanism. Oxysterol-resistant cells demonstrated no significant difference in the expression of several genes previously implicated in oxysterol resistance, but expressed the bcl-2 gene at significantly lower levels than those observed in control cells. We identified three novel genes differentially expressed in resistant cells when compared to HL60 control cells. Taken together, the results of this study reveal potentially novel mechanisms of oxysterol cytotoxicity and resistance, and indicate that cytotoxicity of 25-OHC, 7β-OHC and 7κ-C occur by independent, yet overlapping mechanisms.

Mechanisms of dynamic strain induced transformation and post-deformation evolution

In this study, a novel experimental approach was applied to study the mechanism of the equiaxed shape retention in dynamic strain induced ferrite during deformation. The post-deformation ferrite evolution in both static and dynamic transformation was studied. The refinement potential and the origin of their differences in both mechanisms were analysed.