Browsing by Author "Hollings, A"

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    Investigating the role of Zn in glucose regulation using x-ray fluorescence microscopy and x-ray absorption near-edge structure spectroscopy
    (Australian Nuclear Science and Technology Organisation, 2021-11-24) Ellison, G; Bambery, KR; Hackett, MJ; Hollings, A; Howard, DJ; Sharif, A; Takechi, RN
    Zinc plays an important function in glucose regulation, particularly within pancreatic islets, the anatomical home of the glucose regulating hormones insulin and glucagon. Glucose dysregulation is a significant contributor to the epidemic of metabolic diseases, including diabetes, that affect an increasing number of people. Zn is found in very high (mM) concentrations in insulin-secreting β-cells, where it facilitates insulin synthesis and storage, and is co-secreted with insulin, subsequently acting as a signalling molecule. Zn dysregulation is often coincident with impairment of insulin secretion, but little is known about the nature of the changes. Since a subset of the pool of Zn in islets is labile, it is difficult to image in its in vivo situation using conventional techniques such as histochemistry. Not only do preparation steps such as washing displace Zn, but some forms in which it exists are not readily discernible using conventional microscopy techniques. X-ray fluorescence microscopy (XFM) and X-ray absorption near-edge structure spectroscopy (XANES) offer several advantages in that tissue preparation is minimal, facilitating the conservation of native states, and all forms of Zn are not only detectable, but are able to be discriminated by matching spectra against an existing library of Zn forms. Here we report the preliminary results from our study of Zn speciation and elemental mapping in murine islets from healthy or diabetes-prone animals in two age groups, 14 (denoted young) or 28 (old) weeks. This work uses a library of biologically relevant Zn forms created in our laboratory, and contributes to our understanding of the role of Zn in glucose regulation in health and disease, including aging. © The Authors
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    Spectroscopic analysis of age-related changes in the brain lateral ventricles during ageing
    (Australian Nuclear Science and Technology Organisation, 2021-11-24) Hollings, A; Hackett, MJ; Tobin, MJ; Klein, AR; Vongsvivut, JP; de Jonge, MD; Bone, S; Webb, S; Lam, V; Takechi, R; Mamo, J
    Alzheimer’s disease is the most common form of dementia and poses significant health and economic concerns. Currently, the disease has no cure, and it is expected that over 1 million people could be affected by 2058 in Australia alone. The content and distribution of metals such as Fe, Cu, Zn is known to change in the ageing brain and thus, increased understanding of the mechanistic role of metal dis-homeostasis may illuminate new therapeutic strategies. The brain lateral ventricles, which play a role in controlling metal and ion transport, have shown increasing levels of copper surrounding their walls with ageing. As a redox active metal, copper can induce oxidative stress which is a process that occurs during Alzheimer’s disease onset and progression. Our research group has been interested in determining whether the age-related elevation of copper surrounding the lateral ventricles is inducing oxidative stress in that region. In this study, we have utilised X-Ray Absorption Spectroscopy (XAS) at the Stanford Synchrotron Radiation Lightsource to analyse different chemical forms of sulfur and measure oxidative stress by analysis of disulfides. Additionally, we used the infrared microscopy beamline at the Australian Synchrotron to identify whether any other markers of oxidative stress were present around the ventricles. Further insights into metal dis-homeostasis and its influence on other biochemical pathways, may help to reveal some of the neurochemical mechanisms involved in progression of Alzheimer’s disease. In turn, this may help pave the way for potential preventative or therapeutic models.