South Australian Health Medical Research Institute

Adelaide, Australia

South Australian Health Medical Research Institute

Adelaide, Australia
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Gonzalez-Chica D.A.,University of Adelaide | Dal Grande E.,University of Adelaide | Bowden J.,South Australian Health & Medical Research Institute | Musker M.,South Australian Health & Medical Research Institute | And 2 more authors.
Preventive Medicine | Year: 2017

This study investigated the achievement of lifestyle recommendations and use of preventive medication in people who 1) are obese, 2) or have metabolic risk factors (hypertension, dyslipidaemia, and/or diabetes), 3) or have cardiovascular disease (CVD), 4) or are healthy, and the impact this preventive health care had on their ‘Health-Related Quality of Life’ (HRQoL). Cross-sectional survey conducted in 2015 with 2379 South Australian adults (57.1 ± 14 years; 51.7% females). Physical (PCS) and mental components scores (MCS) of HRQoL were assessed using the SF-12 questionnaire. Although adequate fruit/vegetable intake was lower among individuals with CVD (29.8%; p = 0.049), this behaviour was associated with a better MCS. Adequate physical activity level was lower among those with metabolic risk factors (29.5%) or CVD (31.0%; p = 0.008), but independent of their clinical condition, this behaviour was associated with a higher PCS. Individuals with CVD were less likely to have adequate alcohol consumption (63.4%; p = 0.026), but those achieving this recommendation had poorer PCS. Non-smoking was similar in all groups (85%; p = 0.768) and was associated with a better MCS only among healthy individuals and those with CVD. In all the groups, individuals achieving all the lifestyle recommendations had a better PCS. Only 48.2% of individuals with CVD reported combined use of antithrombotic, antihypertensive, and antilipidemic drugs, but the use of these medications was not associated with HRQoL. In conclusion, the vast majority of individuals at risk of or with CVD did not achieve preventive recommendations, and only the adequacy of uptake of all recommended lifestyle behaviours showed consistent benefits for PCS and MCS. © 2017 Elsevier Inc.

Klaric T.S.,University of Adelaide | Jaehne E.J.,University of Adelaide | Koblar S.A.,University of Adelaide | Baune B.T.,University of Adelaide | Lewis M.D.,South Australian Health & Medical Research Institute
Behavioural Brain Research | Year: 2017

In addition to causing widespread cell death and loss of brain function, cerebral ischaemia also induces extensive neuroplasticity. In humans, stroke is often accompanied by severe cognitive and psychiatric changes that are thought to arise as a consequence of this infarct-induced remodelling. A candidate for producing these post-stroke neuropsychiatric changes is Npas4, an activity-dependent transcription factor involved in synaptic plasticity whose expression is aberrantly up-regulated following ischaemic injury. In this study we investigated the role of Npas4 in modulating these stroke-induced neuropsychiatric responses by comparing the performance of wildtype and Npas4−/− mice in various cognitive and behavioural tasks in a photochemical model of focal cortical stroke. We show that this stroke model results in impaired spatial recognition memory and a reduction in despair-like behaviour that affect both genotypes to a similar degree. Moreover, mice lacking Npas4 also show differences in some aspects of post-stroke sociability and anxiety. Specifically, we show that while stroke had no effect on anxiety levels in wildtype mice, Npas4−/− mice became significantly more anxious following stroke. In addition, Npas4−/− mice retained a greater level of sociability in the acute post-stroke period in comparison to their wildtype littermates. Thus, our findings suggest that Npas4 may be involved in post-stroke psychiatric changes related to anxiety and sociability. © 2016

Choy F.C.,University of Adelaide | Klaric T.S.,University of Adelaide | Koblar S.A.,University of Adelaide | Lewis M.D.,University of Adelaide | Lewis M.D.,South Australian Health & Medical Research Institute
Molecular Neurobiology | Year: 2017

Neuronal PAS domain protein 4 (Npas4) is a brain-specific transcription factor whose expression is enriched in neurogenic regions of the brain. In addition, it was demonstrated that Npas4 expression is dynamic and highly regulated during neural differentiation of embryonic stem cells (ESCs). While these findings implicate a role for Npas4 in neurogenesis, the underlying mechanisms of regulation remain unknown. Given that growing evidence suggests that microRNAs (miRNAs) play important roles in both embryonic and adult neurogenesis, we reasoned that miRNAs are good candidates for regulating Npas4 expression during neural differentiation of ESCs. In this study, we utilized the small RNA sequencing method to profile miRNA expression during neural differentiation of mouse ESCs. Two differentially expressed miRNAs were identified to be able to significantly reduce reporter gene activity by targeting the Npas4 3’UTR, namely miR-744 and miR-224. More importantly, ectopic expression of these miRNAs during neural differentiation resulted in downregulation of endogenous Npas4 expression. Subsequent functional analysis revealed that overexpression of either miR-744 or miR-224 delayed early neural differentiation, reduced GABAergic neuron production and inhibited neurite outgrowth. Collectively, our findings indicate that Npas4 not only functions at the early stages of neural differentiation but may also, in part, contribute to neuronal subtype specification and neurite development. © 2016, Springer Science+Business Media New York.

Sugiyama T.,University of South Australia | Howard N.J.,University of South Australia | Paquet C.,University of South Australia | Paquet C.,University Institute of Mental Health | And 5 more authors.
Journal of Urban Health | Year: 2015

Residents of areas with lower socioeconomic status (SES) are known to be less physically active during leisure time. Neighborhood walkability has been shown to be related to recreational walking equally in low and high SES areas. This cross-sectional study tested whether associations of specific environmental attributes, measured objectively and subjectively, with walking for recreation were moderated by area-level SES. The data of the North West Adelaide Health Study collected in 2007 (n = 1500, mean age 57) were used. Self-reported walking frequency was the outcome of the study. Environmental exposure measures included objectively measured walkability components (residential density, intersection density, land use mix, and net retail area ratio) and perceived attributes (access to destinations, neighborhood esthetics, walking infrastructure, traffic/barriers, and crime safety). Participants’ suburbs were categorized into low and high SES areas using an indicator of socioeconomic disadvantage. Low SES areas had lower scores in residential density, neighborhood esthetics, walking infrastructure, traffic/barriers, and crime safety. Recreational walking was associated with residential density, access to destinations, esthetics, traffic/barriers, and crime safety. Effect modification was observed for two attributes (out of nine): residential density was associated with walking only in low SES areas, while walking infrastructure was associated with walking only in high SES areas. The associations of neighborhood environmental attributes with recreational walking were largely consistent across SES groups. However, low SES areas were disadvantaged in most perceived environmental attributes related to recreational walking. Improving such attributes in low SES neighborhoods may help close socioeconomic disparities in leisure time physical activity. © 2015, The New York Academy of Medicine.

Netting M.J.,Womens and Childrens Health Research Institute | Netting M.J.,University of Adelaide | Middleton P.F.,University of Adelaide | Makrides M.,Womens and Childrens Health Research Institute | And 2 more authors.
Nutrition | Year: 2014

Objectives: The aim of this study was to investigate the relationship between maternal diet during pregnancy and lactation and development of atopic disorders in childhood. Methods: We included studies published up to August 2011 that assessed food-based maternal dietary interventions or that examined associations between maternal dietary intake during pregnancy and/or lactation and allergic outcomes (eczema, asthma, hay fever, and sensitization) in their children. Results: We included 42 studies (>40 000 children): 11 intervention studies (including 7 randomized control trials), 26 prospective cohort studies, 4 retrospective cohort studies, and 1 case-control study. In the randomized control trials, no significant difference was noted overall in the prevalence of eczema and asthma in the offspring of women on diets free from common food allergens during pregnancy. The prospective cohorts investigated a large number of potential associations, but reported few significant associations between maternal dietary intake and development of allergy. Maternal diets rich in fruits and vegetables, fish, and foods containing vitamin D and Mediterranean dietary patterns were among the few consistent associations with lower risk for allergic disease in their children. Foods associated with higher risk included vegetable oils and margarine, nuts, and fast food. Conclusion: This review did not find widespread or consistent links between mothers' dietary intake and atopic outcomes in their children. However, maternal consumption of Mediterranean dietary patterns, diets rich in fruits and vegetables, fish, and vitamin D-containing foods were suggestive of benefit, requiring further evaluation. © 2014 Elsevier Inc.

PubMed | Aix - Marseille University, French National Institute for Agricultural Research and South Australian Health &Medical Research Institute
Type: | Journal: Scientific reports | Year: 2016

It is well known that the GCN2 and mTORC1 signaling pathways are regulated by amino acids and share common functions, in particular the control of translation. The regulation of GCN2 activity by amino acid availability relies on the capacity of GCN2 to sense the increased levels of uncharged tRNAs upon amino acid scarcity. In contrast, despite recent progress in the understanding of the regulation of mTORC1 by amino acids, key aspects of this process remain unsolved. In particular, while leucine is well known to be a potent regulator of mTORC1, the mechanisms by which this amino acid is sensed and control mTORC1 activity are not well defined. Our data establish that GCN2 is involved in the inhibition of mTORC1 upon leucine or arginine deprivation. However, the activation of GCN2 alone is not sufficient to inhibit mTORC1 activity, indicating that leucine and arginine exert regulation via additional mechanisms. While the mechanism by which GCN2 contributes to the initial step of mTORC1 inhibition involves the phosphorylation of eIF2, we show that it is independent of the downstream transcription factor ATF4. These data point to a novel role for GCN2 and phosphorylation of eIF2 in the control of mTORC1 by certain amino acids.

PubMed | South Australian Health & Medical Research Institute, University of Adelaide and Flinders University
Type: | Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience | Year: 2016

Human adult dental pulp stem cells (DPSC) are a heterogeneous stem cell population, which are able to differentiate down neural, chondrocyte, osteocyte and adipocyte lineages. We studied the expression pattern of p75 neurotrophin receptors (p75NTR), a marker of neural stem cells, within human DPSC populations from eight donors. p75NTR are expressed at low levels (<10%) in DPSC. Importantly, p75(+) DPSC represent higher expression levels of SOX1 (neural precursor cell marker), SOX2 (cell pluripotency marker) and nestin (neural stem cell marker) in comparison to p75(-) DPSC. Our results suggest that p75(+) hDPSC may denote a subpopulation with greater neurogenic potential.

PubMed | South Australian Health & Medical Research Institute, University of South Australia and Flinders Center for Innovation in Cancer
Type: | Journal: Asia-Pacific journal of clinical oncology | Year: 2016

Limited data are available on how spiritual needs of patients with cancer care are addressed by Australian oncologists. The objectives of this study were to explore the current practice, preparedness and education of Australian oncologists and oncology trainees on the provision of spiritual care for their patients with cancer.Participants were recruited through oncology professional organizations and data collected through an anonymous online survey using a validated questionnaire.Responses from a total of 69 medical professionals were suitable for data analysis. The majority of the respondents had encountered patients with spiritual care needs during clinical consultations. Only 45% of the respondents perceived that they were able to meet the spiritual needs of their patients. Barriers to providing spiritual care identified a lack of time, education and understanding of spirituality and spiritual care in the context of health. Only 25% stated they had received some form of education on spiritual care with 7% of these stated that the education was adequate. Participants believed that they learnt how to provide spiritual care on the job or because of their self-interest, and not as formal training.The results of this study indicate that Australian oncology professionals often encounter patients with spiritual care needs in their clinical practice. Despite this finding, only a small proportion of the medical professionals had education on spiritual care during their professional training. Forty-five percent of the medical practitioners believed that they were able to partly or completely meet their patients spiritual care needs.

PubMed | South Australian Health & Medical Research Institute and Shanghai University of Traditional Chinese Medicine
Type: | Journal: Oncotarget | Year: 2016

Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (m) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1.

PubMed | University of Southampton, South Australian Health &Medical Research Institute and Zhejiang University
Type: | Journal: Scientific reports | Year: 2016

The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease.

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