Expression of PTRF in PC3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways

Expression of caveolin-1 is up-regulated in prostate cancer metastasis and is associated with aggressive recurrence of the disease. Intriguingly, caveolin-1 is also secreted from prostate cancer cell lines and has been identified in secreted prostasomes. Caveolin-1 is the major structural component of the plasma membrane invaginations called caveolae. Co-expression of the coat protein Polymerase I and transcript release factor (PTRF) is required for caveolae formation. We recently found that expression of caveolin-1 in the aggressive prostate cancer cell line PC-3 is not accompanied by PTRF, leading to noncaveolar caveolin-1 lipid rafts. Moreover, ectopic expression of PTRF in PC-3 cells sequesters caveolin-1 into caveolae. Here we quantitatively analyzed the effect of PTRF expression on the PC-3 proteome using stable isotope labeling by amino acids in culture and subcellular proteomics. We show that PTRF reduced the secretion of a subset of proteins including secreted proteases, cytokines, and growth regulatory proteins, partly via a reduction in prostasome secretion. To determine the cellular mechanism accounting for the observed reduction in secreted proteins we analyzed total membrane and the detergent-resistant membrane fractions. Our data show that PTRF expression selectively impaired the recruitment of actin cytoskeletal proteins to the detergent-resistant membrane, which correlated with altered cholesterol distribution in PC-3 cells expressing PTRF. Consistent with this, modulating cellular cholesterol altered the actin cytoskeleton and protein secretion in PC-3 cells. Intriguingly, several proteins that function in ER to Golgi trafficking were reduced by PTRF expression. Taken together, these results suggest that the noncaveolar caveolin-1 found in prostate cancer cells generates a lipid raft microenvironment that accentuates secretion pathways, possibly at the step of ER sorting/exit. Importantly, these effects could be modulated by PTRF expression.

A simulation-based training system for surgical wound debridement

A simulation-based training system for surgical wound debridement was developed and comprises a multimedia introduction, a surgical simulator (tutorial component), and an assessment component. The simulator includes two PCs, a haptic device, and mirrored display. Debridement is performed on a virtual leg model with a shallow laceration wound superimposed. Trainees are instructed to remove debris with forceps, scrub with a brush, and rinse with saline solution to maintain sterility. Research and development issues currently under investigation include tissue deformation models using mass-spring system and finite element methods; tissue cutting using a high-resolution volumetric mesh and dynamic topology; and accurate collision detection, cutting, and soft-body haptic rendering for two devices within the same haptic space.

Telehealth for nursing homes: the utilization of specialist services for residential care

Specialist care consultations were identified by two research nurses using documentation in patient records, appointment diaries, electronic billing services and on-site observations at a 441-bed long term care facility. Over a six-month period there were 3333 consultations (a rate of 1511 consultations per year per 100 beds). Most consultations were for general practice (n = 2589, 78%); these consultations were mainly on site (99%), with only 27 taking place off site. There were 744 consultations for specialities other than general practice. A total of 146 events related to an emergency or unplanned hospital admission. The remaining medical consultations (n = 598, 18%) related to 23 medical specialities. The largest number of consultations were for surgery (n = 106), podiatry (n = 100), nursing services including wound care (n = 74), imaging (n = 41) and ophthalmology (n = 40). Many services which are currently being provided on site to metropolitan long-term care facilities could be provided by telehealth in both urban and rural facilities.

Flotation process response of Ok Tedi fluorine bearing minerals

Orebodies at Ok Tedi contain a number of different fluorine bearing minerals. Some of these minerals report to concentrate and are responsible for the presence of the penalty element, fluorine, within the concentrate. Previous analytical work has tended to examine geological samples for content, rather than determine the metallurgical behaviour of the different mineralogical species. This investigation utilised X-Ray Diffraction combined with Scanning Electron Microscope/Electron Microprobe to identify the fluorine bearing minerals in flotation test products. Seven fluorine bearing minerals were identified, viz., talc, phlogopite, amphibole (tremolite and actinolite), sphene, apatite, biotite and clay. Talc was found exclusively in the skarn ore type. Phlogopite and amphiboles (tremolite and actinolite) were found to occur in both skarn and porphyry ores, while sphene, apatite, biotite and clay were found only in the porphyry ores. Of the fluorine bearing minerals observed, only talc exhibited natural hydrophobicity to any significant degree. Phlogopite and the amphibole minerals were found to be hydrophillic, whilst the remaining minerals occurred in insufficient quantities to determine the flotation behaviour. Ok Tedi copper concentrate fluorine content prior to skarn ore treatment in the mill (typically 350ppm) was previously identified as deriving from phlogopite, while talc was believed to be the source of intermittent high concentrate fluorine contents when skarn ores were treated. This paper provides supporting evidence for this belief, and reports the nature of fluorine bearing mineral flotation behaviour.

Offsetting methane emissions : an alternative to emission equivalence metrics

It is widely recognised that defining trade-offs between greenhouse gas emissions using ‘emission equivalence’ based on global warming potentials (GWPs) referenced to carbon dioxide produces anomalous results when applied to methane. The short atmospheric lifetime of methane, compared to the timescales of CO2 uptake, leads to the greenhouse warming depending strongly on the temporal pattern of emission substitution. We argue that a more appropriate way to consider the relationship between the warming effects of methane and carbon dioxide is to define a ‘mixed metric’ that compares ongoing methane emissions (or reductions) to one-off emissions (or reductions) of carbon dioxide. Quantifying this approach, we propose that a one-off sequestration of 1 t of carbon would offset an ongoing methane emission in the range 0.90–1.05 kg CH4 per year. We present an example of how our approach would apply to rangeland cattle production, and consider the broader context of mitigation of climate change, noting the reverse trade-off would raise significant challenges in managing the risk of non-compliance. Our analysis is consistent with other approaches to addressing the criticisms of GWP-based emission equivalence, but provides a simpler and more robust approach while still achieving close equivalence of climate mitigation outcomes ranging over decadal to multi-century timescales.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.

Epigenetic regulation of glucose transporters in non-small cell lung cancer

Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

The increasing cost of healthy food

OBJECTIVE: To assess changes in the cost and availability of a standard basket of healthy food items (the Healthy Food Access Basket [HFAB]) in Queensland. METHODS: Analysis of five cross-sectional surveys (1998, 2000, 2001, 2004 and 2006) describes changes over time. Eighty-nine stores in five remoteness categories were surveyed during May 2006. For the first time a sampling framework based on randomisation of towns throughout the state was applied and the survey was conducted by Queensland Treasury. RESULTS: Compared with the costs in major cities, in 2006 the mean cost of the HFAB was $107.81 (24.2%) higher in very remote stores in Queensland, but $145.57 (32.6%) higher in stores more than 2,000 kilometres from Brisbane. Over six years the cost of the HFAB has increased by around 50% ($148.87) across Queensland and, where data was available, by more than the cost of less healthy alternatives. The Consumer Price Index for food in Brisbane increased by 32.5% over the same period. CONCLUSIONS AND IMPLICATIONS: Australians, no matter where they live, need access to affordable, healthy food. Issues of food security in the face of rising food costs are of concern particularly in the current global economic downturn. There is an urgent need to nationally monitor, but also sustainably address the factors affecting the price of healthy foods, particularly for vulnerable groups who suffer a disproportionate burden of poor health.

The increasing cost of the basic foods required to promote health in Queensland

Objective: To assess changes in the cost and availability of a standard basket of healthy food items (the Healthy Food Access Basket [HFAB]) in Queensland over time. Design and participants: A series of four cross-sectional surveys (in 1998, 2000, 2001 and 2004) describing the cost and availability of foods in the HFAB over time. In the latest survey, 97 Queensland food stores across the five Australian Bureau of Statistics remoteness categories were compared. Main outcome measures: Cost comparisons for HFAB items by remoteness category for the 97 stores surveyed in 2004; changes in cost and availability of foods in the 81 stores surveyed since 2000; comparisons of food prices in the 56 stores surveyed in 1998, 2000, 2001 and 2004. Results: In 2004, the Queensland mean cost of the HFAB was $395.28 a fortnight. The cost of the HFAB was 29.6%($113.89) higher in “very remote” areas than in “major cities” (P<0.001). Between 2001 and 2004, the Queensland mean cost of the HFAB increased by 14.0% ($48.45), while in very remote areas the cost increased by 18.0% ($76.93) (P<0.001). Since 2000, the annualised per cent increase in cost of the HFAB has been higher than the increase in Consumer Price Index for food in Brisbane. The cost of healthy foods has risen more than the cost of some less nutritious foods, so that the latter are now relatively more affordable. Conclusions: Consumers, particularly those in very remote locations, need to pay substantially more for basic healthy foods than they did a few years ago. Higher prices are likely to be a barrier to good health among people of low socioeconomic status and other vulnerable groups. Interventions to make basic healthy food affordable and accessible to all would help reduce the high burden of chronic disease.

Food availability, cost disparity and improvement in relation to accessibility and remoteness in Queensland

This study is the first to describe disparity and change in the food supply between metropolitan, rural and remote stores by Accessibility/Remoteness Index of Australia (ARIA)1 category. A total of 92 stores (97% response rate) within five aggregate ARIA categories participated throughout Queensland in 2000. There was a strong association between ARIA category and the cost of the basket of basic foods, with prices being significantly higher (20% and 31% respectively) in the ‘remote’ and ‘very remote’ categories than in the ‘highly accessible’ category. The association with ARIA was less marked for fruit and vegetables than for other food groups, but not for tobacco and take-away food items. Basic food items were less available in the more remote stores. Over the past two years, relative improvements in food prices have been seen in stores in the ‘very remote’ category, with observed increases less than the consumer price index (CPI) for food. Some factors which may have contributed to this improvement are discussed.

A systematic review of telemedicine services for residents in long term care facilities

We conducted a systematic review of the literature on telemedicine use in long-term care facilities (LTCFs) and assessed the quality of the published evidence. A database search identified 22 papers which met the inclusion criteria. The quality of the studies was assessed and if they contained economic data, they were rated according to standard criteria. The clinical services provided by telemedicine included allied health (n = 5), dermatology (3), general practice (4), neurology (2), geriatrics (1), psychiatry (4) and multiple specialities (3). Most studies (17) employed real-time telemedicine using videoconferencing. The remaining five used store and forward telemedicine. The papers focused on economics (3), feasibility (9), stakeholder satisfaction (12), reliability (5) and service implementation (2). Overall, the quality of evidence for telemedicine in LTCFs was low. There was only one small randomised controlled trial (RCT). Most studies were observational and qualitative, and focused on utilisation. They were mainly based on surveys and interviews of stakeholders. A few studies evaluated the cost associated with implementing telemedicine services in LTCFs. The present review shows that there is evidence for feasibility and stakeholder satisfaction in using telemedicine in LTCFs in a number of clinical specialities.

Circles of care : should community development redefine the practice of palliative care?

Specialist palliative care, within hospices in particular, has historically led and set the standard for caring for patients at end of life. The focus of this care has been mostly for patients with cancer. More recently, health and social care services have been developing equality of care for all patients approaching end of life. This has mostly been done in the context of a service delivery approach to care whereby services have become increasingly expert in identifying health and social care need and meeting this need with professional services. This model of patient centred care, with the impeccable assessment and treatment of physical, social, psychological and spiritual need, predominantly worked very well for the latter part of the 20th century. Over the last 13 years, however, there have been several international examples of community development approaches to end of life care. The patient centred model of care has limitations when there is a fundamental lack of integrated community policy, development and resourcing. Within this article, we propose a model of care which identifies a person with an illness at the centre of a network which includes inner and outer networks, communities and service delivery organisations. All of these are underpinned by policy development, supporting the overall structure. Adoption of this model would allow individuals, communities, service delivery organisations and policy makers to work together to provide end of life care that enhances value and meaning for people at end of life, both patients and communities alike.

Working together-apart : exploring the relationships between formal and informal care networks for people dying at home

Introduction Informal caring networks contribute significantly to end-of-life (EOL) care in the community. However, to ensure that these networks are sustainable, and unpaid carers are not exploited, primary carers need permission and practical assistance to gather networks together and negotiate the help they need. Our aim in this study was to develop an understanding of how formal and informal carers work together when care is being provided in a dying person's home. We were particularly interested in formal providers’ perceptions and knowledge of informal networks of care and in identifying barriers to the networks working together. Methods Qualitative methods, informed by an interpretive approach, were used. In February-July 2012, 10 focus groups were conducted in urban, regional, and rural Australia comprising 88 participants. Findings Our findings show that formal providers are aware, and supportive, of the vital role informal networks play in the care of the dying at home. A number of barriers to formal and informal networks working together more effectively were identified. In particular, we found that the Australian policy of health-promoting palliative is not substantially translating to practice. Conclusion Combinations of formal and informal caring networks are essential to support people and their primary carers. Formal service providers do little to establish, support, or maintain the informal networks although there is much goodwill and scope for them to do so. Further re-orientation towards a health-promoting palliative care and community capacity building approach is suggested.

Mid-Holocene sea-level and coral reef demise : U-Th dating of subfossil corals in Moreton Bay, Australia

It is increasingly apparent that sea-level data (e.g. microfossil transfer functions, dated coral microatolls and direct observations from satellite and tidal gauges) vary temporally and spatially at regional to local scales, thus limiting our ability to model future sea-level rise for many regions. Understanding sealevel response at ‘far-field’ locations at regional scales is fundamental for formulating more relevant sea-level rise susceptibility models within these regions under future global change projections. Fossil corals and reefs in particular are valuable tools for reconstructing past sea levels and possible environmental phase shifts beyond the temporal constraints of instrumental records. This study used abundant surface geochronological data based on in situ subfossil corals and precise elevation surveys to determine previous sea level in Moreton Bay, eastern Australia, a far-field site. A total of 64 U-Th dates show that relative sea level was at least 1.1 m above modern lowest astronomical tide (LAT) from at least ˜6600 cal. yr BP. Furthermore, a rapid synchronous demise in coral reef growth occurred in Moreton Bay ˜5800 cal. yr BP, coinciding with reported reef hiatus periods in other areas around the Indo-Pacific region. Evaluating past reef growth patterns and phases allows for a better interpretation of anthropogenic forcing versus natural environmental/climatic cycles that effect reef formation and demise at all scales and may allow better prediction of reef response to future global change.