CD151 is associated with prostate cancer cell invasion and lymphangiogenesis in vivo

CD151, a member of the tetraspanin family, is associated with regulation of migration of normal and tumour cells via cell surface microdomain formation. CD151 was found in our laboratory to have a prognostic value in prostate cancer and is a promoter of prostate cancer migration and invasion. These roles involve association with integrins on both cell-cell and cell-stroma levels. Furthermore, CD151 plays a role in endothelial cell motility. CD151 expression was examined in three commonly used prostate cancer cell lines. We investigated CD151 expression, angiogenesis (microvessel density; MVD) and lymphangiogenesis (lymphatic vessel density; LVD) in an orthotopic xenograft model of prostate cancer in matched tumours from primary and secondary sites. CD151 was found to be heterogeneously expressed across different prostate cancer cell lines and the levels of CD151 expression were significantly higher in the highly tumorigenic, androgen-insensitive cells PC-3 and DU-145 compared to the androgen-sensitive cell line LNCaP (P<0.05). The majority of in vivo xenografts developed pelvic lymph node metastases. Importantly, primary tumours that developed metastasis had significantly higher CD151 expression and MVD compared to those which did not develop metastasis (P<0.05). We identified, for the first time, that CD151 expression is associated with LVD in prostate cancer. These findings underscore the potential role of CD151 and angiogenesis in the metastatic potential of prostate cancer. CD151 has a prognostic value in this mouse model of prostate cancer and may play a role in lymphangiogenesis. CD151 is likely an important regulator of cancer cell communication with the surrounding microenvironment.

Are hypoxia or modulus causes of contact lens-associated keratitis?

In this, the 10th anniversary of the introduction of silicone hydrogel contact lenses onto the market, it is perhaps timely to attempt to reconcile the apparently disparate results from different authors in relation to the incidence of keratitis with silicone hydrogel lenses and indeed, with contact lenses in general. In attempting to understand the findings of these various studies, we propose that consideration be given to the competing effects of an improved physiological response due to increased corneal oxygenation with these lenses versus their mechanical impact...

Exposure to solar ultraviolet radiation is associated with a decreased folate status in women of childbearing age

In vitro studies indicate that folate in collected human blood is vulnerable to degradation after exposure to ultraviolet (UV) radiation. This has raised concerns about folate depletion in individuals with high sun exposure. Here, we investigate the association between personal solar UV radiation exposure and serum folate concentration, using a three-week prospective study that was undertaken in females aged 18–47 years in Brisbane, Australia (153 E, 27 S). Following two weeks of supplementation with 500 μg of folic acid daily, the change in serum folate status was assessed over a 7-day period of measured personal sun exposure. Compared to participants with personal UV exposures of <200 Joules per day, participants with personal UV exposures of 200–599 and >600 Joules per day had significantly higher depletion of serum folate (p = 0.015). Multivariable analysis revealed personal UV exposure as the strongest predictor accounting for 20% of the overall change in serum folate (Standardised B = −0.49; t = −3.75; p = <0.01). These data show that increasing solar UV radiation exposures reduces the effectiveness of folic acid supplementation. The consequences of this association may be most pronounced for vulnerable individuals, such as women who are pregnant or of childbearing age with high sun exposures.

High dietary diversity is associated with obesity in Sri Lankan adults : an evaluation of three dietary scores

Background Dietary diversity is recognized as a key element of a high quality diet. However, diets that offer a greater variety of energy-dense foods could increase food intake and body weight. The aim of this study was to explore association of diet diversity with obesity in Sri Lankan adults. Methods Six hundred adults aged > 18 years were randomly selected by using multi-stage stratified sample. Dietary intake assessment was undertaken by a 24 hour dietary recall. Three dietary scores, Dietary Diversity Score (DDS), Dietary Diversity Score with Portions (DDSP) and Food Variety Score (FVS) were calculated. Body mass index (BMI) ≥ 25 kg.m-2 is defined as obese and Asian waist circumference cut-offs were used diagnosed abdominal obesity. Results Mean of DDS for men and women were 6.23 and 6.50 (p=0.06), while DDSP was 3.26 and 3.17 respectively (p=0.24). FVS values were significantly different between men and women 9.55 and 10.24 (p=0.002). Dietary diversity among Sri Lankan adults was significantly associated with gender, residency, ethnicity, education level but not with diabetes status. As dietary scores increased, the percentage consumption was increased in most of food groups except starches. Obese and abdominal obese adults had the highest DDS compared to non obese groups (p<0.05). With increased dietary diversity the level of BMI, waist circumference and energy consumption was significantly increased in this population. Conclusion Our data suggests that dietary diversity is positively associated with several socio-demographic characteristics and obesity among Sri Lankan adults. Although high dietary diversity is widely recommended, public health messages should emphasize to improve dietary diversity in selective food items.

Axial elongation associated with biomechanical factors during near work

Purpose: To investigate the changes occurring in the axial length, choroidal thickness and anterior biometrics of the eye during a 10 minute near task performed in downward gaze. Methods: Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure ocular biometrics in downward gaze, an optical biometer was inclined on a custom built, height and tilt adjustable table. Baseline measures were collected after each subject performed a distance primary gaze control task for 10 mins, to provide wash-out period for prior visual tasks before each of three different accommodation/gaze conditions. These other three conditions included a near task (2.5 D) in primary gaze, and a near (2.5 D) and a far (0 D) accommodative task in downward gaze (25°), all for 10 mins duration. Immediately after, and then 5 and 10 mins from the commencement of each trial, measurements of ocular biometrics (e.g. anterior biometrics, axial length, choroidal thickness and retinal thickness) were obtained. Results: Axial length increased with accommodation and was significantly greater for downward gaze with accommodation (mean change ± SD 23 ± 13 µm at 10 mins) compared to primary gaze with accommodation (mean change 8 ± 15 µm at 10 mins) (p < 0.05). A small amount of choroidal thinning was also found during accommodation that was statistically significant in downward gaze (13 ± 14 µm at 10 mins, p < 0.05). Accommodation in downward gaze also caused greater changes in anterior chamber depth and lens thickness compared to accommodation in primary gaze. Conclusion: Axial length, choroidal thickness and anterior eye biometrics change significantly during accommodation in downward gaze as a function of time. These changes appear to be due to the combined influence of biomechanical factors (i.e. extraocular muscle forces, ciliary muscle contraction) associated with near tasks in downward gaze.

Retinal nerve fibre layer thickness is associated with higher risk of foot ulceration in diabetic peripheral neuropathy

Purpose To evaluate the association between retinal nerve fibre layer (RNFL) thickness and diabetic peripheral neuropathy in people with type 2 diabetes, and specifically those at higher risk of foot ulceration. Methods RNFL thicknesses was measured globally and in four quadrants (temporal, superior, nasal and inferior) at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). Severity of neuropathy was assessed using the Neuropathy Disability Score (NDS). Eighty-two participants with type 2 diabetes were stratified according to NDS scores (0-10) as: none, mild, moderate, and severe neuropathy. A control group was additionally included (n=17). Individuals with NDS≥ 6 (moderate and severe neuropathy) have been shown to be at higher risk of foot ulceration. A linear regression model was used to determine the association between RNFL and severity of neuropathy. Age, disease duration and diabetic retinopathy levels were fitted in the models. Independent t-test was employed for comparison between controls and the group without neuropathy, as well as for comparison between groups with higher and lower risk of foot ulceration. Analysis of variance was used to compare across all NDS groups. Results RNFL thickness was significantly associated with NDS in the inferior quadrant (b= -1.46, p=0.03). RNFL thicknesses globally and in superior, temporal and nasal quadrants did not show significant associations with NDS (all p>0.51). These findings were independent of the effect of age, disease duration and retinopathy. RNFL was thinner for the group with NDS ≥ 6 in all quadrants but was significant only inferiorly (p<0.005). RNFL for control participants was not significantly different from the group with diabetes and no neuropathy (superior p=0.07, global and all other quadrants: p>0.23). Mean RNFL thickness was not significantly different between the four NDS groups globally and in all quadrants (p=0.08 for inferior, P>0.14 for all other comparisons). Conclusions Retinal nerve fibre layer thinning is associated with neuropathy in people with type 2 diabetes. This relationship is strongest in the inferior retina and in individuals at higher risk of foot ulceration.

Patterns of social capital associated with transit oriented development

In policy circles, transit oriented development (TOD) is believed to enhance social capital, however empirical evidence of this relationship is lacking. This research compares levels of social capital between TOD vs. non-TOD areas in Brisbane, Australia. Using a Two Step cluster analysis technique, three types of neighbourhood groupings were identified based on net employment density, net residential density, land use diversity, intersection density, and public transport accessibility: TODs, transit adjacent development (TADs) and traditional suburbs. Two dimensions of social capital were measured (trust and reciprocity, connections with neighbours) based on factor analysis of eight items representing elements of social capital. Multivariate regression analyses were conducted to identify links between the distributions of the dimensions of social capital on areas defined as TODs, TADs, and traditional suburbs controlling for socio-demographics and environmental factors. Results show that individuals living in TODs had a significantly higher level of trust and reciprocity and connections with neighbours compared with residents of TADs. It appears that TODs may foster the development of social sustainability.

Hydrogel microwell arrays allow the assessment of protease-associated enhancement of cancer cell aggregation and survival

Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance.

Conjunctivitis associated with Chlamydia pecorum in three koalas (Phascolarctos cinereus) in the Mount Lofty Ranges, South Australia

Chlamydiosis is a significant factor contributing to the decline of koala (Phascolarctos cinereus) populations in Australia but has not previously been reported in South Australia. We describe conjunctivitis in three wild koalas from South Australia, with Chlamydia pecorum identified by quantitative PCR.

Self-management associated with fatigue in patients with advanced cancer : a prospective longitudinal study

Cancer-related fatigue is one of the most distressing symptoms experienced by patients with advanced cancer. This doctoral study identified that patients with advanced cancer commonly use a number of self-management strategies in response to fatigue, although these strategies had varying levels of effectiveness in reducing the symptom. The study identified that enhancing self-efficacy and managing depressive symptoms are important factors to consider in the design of future interventions to support fatigue self-management.

Psychosocial factors associated with controlling feeding practices of Indian and Australian-Indian mothers

This cross-sectional study examined the association between psychosocial factors (mothers’ perception of own and child weight, maternal self-efficacy in feeding and involvement of the mother-in-law in child-feeding) and controlling feeding practices (monitoring, restriction, pressure to eat and passive feeding). Participants were 531 affluent-Indian mothers in Australia and Mumbai with children aged 1-5 years. The psychosocial variables and feeding practices were measured using a combination of previously validated scales and study-developed items/scales. Multivariable regression analyses were stratified by sample (Australia and Mumbai) to investigate psychosocial factors related to the feeding practices, adjusting for covariates. Self-efficacy in feeding was associated with each of the feeding practices in at least one of the samples (β values between 0.1-0.2, p= 0.04-0.005). The greater involvement of the mother-in-law in child-feeding was related to the higher use of restriction in both samples (β values ≥0.2, p=0.02). In contrast, maternal weight perceptions were not consistently associated with feeding practices in either sample. The findings highlighted that unique (self-efficacy in feeding) and culturally-specific (involvement of the mother-in-law) variables not extensively researched within the context of child-feeding were important factors associated with Indian mothers’ feeding practices. Greater consideration of these factors may be required when tailoring child-feeding interventions for Indian mothers.

Phenotypic changes associated with RNA interference silencing of chalcone synthase in apple (Malus × domestica)

We have identified in apple (Malus × domestica) three chalcone synthase (CHS) genes. In order to understand the functional redundancy of this gene family RNA interference knockout lines were generated where all three of these genes were down-regulated. These lines had no detectable anthocyanins and radically reduced concentrations of dihydrochalcones and flavonoids. Surprisingly, down-regulation of CHS also led to major changes in plant development, resulting in plants with shortened internode lengths, smaller leaves and a greatly reduced growth rate. Microscopic analysis revealed that these phenotypic changes extended down to the cellular level, with CHS-silenced lines showing aberrant cellular organisation in the leaves. Fruit collected from one CHS-silenced line was smaller than the 'Royal Gala' controls, lacked flavonoids in the skin and flesh and also had changes in cell morphology. Auxin transport experiments showed increased rates of auxin transport in a CHS-silenced line compared with the 'Royal Gala' control. As flavonoids are well known to be key modulators of auxin transport, we hypothesise that the removal of almost all flavonoids from the plant by CHS silencing creates a vastly altered environment for auxin transport to occur and results in the observed changes in growth and development.

Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes

The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.

An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae

Background The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all the commercially important rosaceous species. Results We use gene specific primers to show that the three MYB activators of apple anthocyanin (MYB10/MYB1/MYBA) are likely alleles of each other. MYB transcription factors, with high sequence identity to the apple gene were isolated from across the rosaceous family (e.g. apples, pears, plums, cherries, peaches, raspberries, rose, strawberry). Key identifying amino acid residues were found in both the DNA-binding and C-terminal domains of these MYBs. The expression of these MYB10 genes correlates with fruit and flower anthocyanin levels. Their function was tested in tobacco and strawberry. In tobacco, these MYBs were shown to induce the anthocyanin pathway when co-expressed with bHLHs, while over-expression of strawberry and apple genes in the crop of origin elevates anthocyanins. Conclusions This family-wide study of rosaceous R2R3 MYBs provides insight into the evolution of this plant trait. It has implications for the development of new coloured fruit and flowers, as well as aiding the understanding of temporal-spatial colour change.

Apple skin patterning is associated with differential expression of MYb10

Background Some apple (Malus × domestica Borkh.) varieties have attractive striping patterns, a quality attribute that is important for determining apple fruit market acceptance. Most apple cultivars (e.g. 'Royal Gala') produce fruit with a defined fruit pigment pattern, but in the case of 'Honeycrisp' apple, trees can produce fruits of two different kinds: striped and blushed. The causes of this phenomenon are unknown. Results Here we show that striped areas of 'Honeycrisp' and 'Royal Gala' are due to sectorial increases in anthocyanin concentration. Transcript levels of the major biosynthetic genes and MYB10, a transcription factor that upregulates apple anthocyanin production, correlated with increased anthocyanin concentration in stripes. However, nucleotide changes in the promoter and coding sequence of MYB10 do not correlate with skin pattern in 'Honeycrisp' and other cultivars differing in peel pigmentation patterns. A survey of methylation levels throughout the coding region of MYB10 and a 2.5 Kb region 5' of the ATG translation start site indicated that an area 900 bp long, starting 1400 bp upstream of the translation start site, is highly methylated. Cytosine methylation was present in all three contexts, with higher methylation levels observed for CHH and CHG (where H is A, C or T) than for CG. Comparisons of methylation levels of the MYB10 promoter in 'Honeycrisp' red and green stripes indicated that they correlate with peel phenotypes, with an enrichment of methylation observed in green stripes. Conclusions Differences in anthocyanin levels between red and green stripes can be explained by differential transcript accumulation of MYB10. Different levels of MYB10 transcript in red versus green stripes are inversely associated with methylation levels in the promoter region. Although observed methylation differences are modest, trends are consistent across years and differences are statistically significant. Methylation may be associated with the presence of a TRIM retrotransposon within the promoter region, but the presence of the TRIM element alone cannot explain the phenotypic variability observed in 'Honeycrisp'. We suggest that methylation in the MYB10 promoter is more variable in 'Honeycrisp' than in 'Royal Gala', leading to more variable color patterns in the peel of this cultivar.