Browsing by Author "Howell, NR"

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    Analysis of hot particle characteristics affecting environmental fate and interaction with living organisms
    (SPERA, 2016-09-09) Johansen, MP; Child, DP; Collins, RN; Hotchkis, MAC; Howell, NR; Payne, TE; Ikeda-Ohno, A; Mokhber-Shahin, L
    The 2nd International Conference on the Sources, Effects and Risks of Ionizing Radiation (SERIR-2) and the 14th Biennial Conference of the South Pacific Environmental Radioactivity Association (SPERA-2016) and will be held in Bali, Indonesia 5-9 September 2016. The South Pacific Environmental Radioactivity Association (SPERA), in conjunction with the Indonesian National Nuclear Energy Agency (BATAN) and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) made the decision to jointly hold these conferences in one week at the same venue to avoid topical overlap and to strengthen regional participation at both events. SERIR2 will be a 1-day conference (5 September) and deals with the efforts to enhance data collection and disseminate scientific findings related to the issues of sources, effects and risks of the ionizing radiation, as well as to seek ways of communicating with stakeholders (scientific communities, regulatory authorities and general public) on those issues. The 14th Biennial Conference of the South Pacific Environmental Radioactivity Association (SPERA), to be held 6-9 September, provides a platform for discussion and debate among scientists on the occurrence, behaviour, impact and measurement of radioactive species present in the environment through natural processes, or resulting from human activities. This international conference facilitates knowledge sharing on environmental radioactivity and related topics of local and global significance. The joint conference will be held 5-9 September 2016, with a welcome reception on 4 September, at the Sanur Paradise Plaza Hotel in Bali. The joint conference will include a one-day workshop on the 6 September on topic(s) to be decided.
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    Assessment of radioactive ‘Hot Particles’ and marine sediment plutonium and americium levels from the Montebello Islands, Western Australia
    (South Pacific Environmental Radioactivity Association, 2018-11-06) Hoffman, M; Johansen, MP; Cook, M; Howell, NR; Kleinschmidt, R; Clegg, JK
    The Montebello islands are an archipelago off the Western Australian coast that to this day display an artificial radioactive legacy. The legacy is the result of nuclear testing from 1952-1956. that produced long-lived radionuclides such as americium (Am-241) and plutonium (Pu-239/240). This study investigated the extent and characteristics of radioactive contamination in marine sediments near the former Operation Hurricane and Operation Mosaic G2 detonation sites in hopes of contributing to future management strategies and updated assessment of health risks to native flora, fauna and human populations. The project was conducted with samples collected in 2015 by the Australian Nuclear Science and Technology Organisation (ANSTO) as two series; Series 1 chosen to monitor the activity from the Operation Mosaic G2 detonation and Series 2 aiming to determine residual activity from the Operation Hurricane HMS Plymouth detonation. Samples were initially sieved to separate the bulk samples into four size-based fractions for analysis of activity fractionation among sediment grain sizes. Radiation counting processes included alpha spectrometry and gamma spectrometry, back-scatter electron mode scanning electron microscopy (BEI-SEM) and photo-stimulated luminescent (PSL) autoradiography to evaluate the overall radiative status of the sediment locations and to investigate the presence of ‘hot’ particles or heterogenous dispersion of radioactivity. Both spectrometry processes revealed that Series 1 Am-241 and Pu-239/240 activity was dispersed preferentially in the two larger fractions (>500 um and 500-200 um). Activity determined as Am241 and Pu-289/240 vi/as observed across Series 2 as well but as values an order of magnitude lower. Environmental plutonium from Series 1 was present in hot particle form, specifically within particles from the more active >500 um [largest] fraction which revealed gamma emissions of the plutonium progeny Am241. imaging and subsequent analysis by BE!-SEM and energy dispersive X-ray spectroscopy (EDS) of the particles revealed that the majority of the particle material was calcium carbonate, indicative of the dominant geology at the detonation site. Study results provide insights into the radioactive characteristics of hot-particles and bulk sediments at the Montebello site. it is believed and hoped that this investigation will aid decisions on the future management of the Montebello wildlife resources and marine park management, and provide insights into potential risks and protective measures for site visitors and researchers.
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    Bioaccumulation kinetics and internal distribution of the fission products radiocaesium and radiostrontium in an estuarine crab
    (Elsevier, 2021-04-15) Cresswell, T; Prentice, E; Howell, NR; Callaghan, PD; Metian, M; Johansen, MP
    Crab has been designated by the ICRP as one of twelve reference/model organisms for understanding the impacts of radionuclide releases on the biosphere. However, radionuclide-crab interaction data are sparse compared with other reference organisms (e.g. deer, earthworm). This study used an estuarine crab (Paragrapsus laevis) to investigate the contribution of water, diet and sediment sources to radionuclide (134Cs and 85Sr) bioaccumulation kinetics using live-animal radiotracing. The distribution of each radionuclide within the crab tissues was determined using dissection, whole-body autoradiography and synchrotron X-ray Fluorescence Microscopy (XFM). When moulting occurred during exposure, it caused significant increases in 85Sr bioaccumulation and efflux of 134Cs under constant aqueous exposure. Dietary assimilation efficiencies were determined as 55 ± 1% for 134Cs and 49 ± 3% for 85Sr. 85Sr concentrated in gonads more than other organs, resulting in proportionally greater radiation dose to the reproductive organs and requires further investigation. 134Cs was found in most soft tissues and was closely associated with S and K. Biodynamic modelling suggested that diet accounted for 90–97% of whole-body 137Cs, while water accounted for 59–81% of 90Sr. Our new data on crab, as a representative invertebrate, improves understanding of the impacts of planned or accidental releases of fission radionuclides on marine ecology. Crown Copyright © 2020 Published by Elsevier B.V.
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    Biofilm-enhanced adsorption of strong and weak cations onto different microplastic sample types: use of spectroscopy, microscopy and radiotracer methods
    (Elsevier, 2019-07-01) Johansen, MP; Cresswell, T; Davis, J; Howard, DL; Howell, NR; Prentice, E
    The adsorption of metals and other elements onto environmental plastics has been previously quantified and is known to be enhanced by surface-weathering and development of biofilms. However, further biofilm-adsorption characterisation is needed with respect to the fate of radionuclides. This study uses spectroscopy, microscopy and radiotracer methods to investigate the adsorption capacity of relatively strong and weak cations onto different microplastic sample types that were conditioned in freshwater, estuarine and marine conditions although marine data were limited. Fourier-transform infrared spectroscopy confirmed that surface oxidation chemistry changes induced by gamma irradiation were similar to those resulting from environmental exposures. Microscopy elemental mapping revealed patchy biofilm development, which contained Si, Al, and O, consistent with microbial-facilitated capture of clays. The plastics+biofilm of all sample types had measurable adsorption for Cs and Sr radiotracers, suggesting environmental plastics act broadly as a sink for the key pervasive environmental radionuclides of 137Cs and 90Sr associated with releases from nuclear activities. Adsorption onto high-density polyethylene plastic types was greater than that on polypropylene. However, in most cases, the adsorption rates of all types of plastic+biofilm were much lower than those of reference sediments and roughly consistent with their relative exchangeable surface areas. Crown Copyright © 2019 Published by Elsevier Ltd.
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    Characterisation of anthropogenic radioactive particles from former weapon test sites in Australia
    (South Pacific Environmental Radioactivity Association, 2018-11-06) Young, EL; Johansen, MP; Child, DP; Hotchkis, MAC; Howell, NR; Pastuovic, Z; Howard, DL; Palmer, T; Davis, J
    Former nuclear test sites on Australian territories such as those at Maralinga and the Montebello islands have been remediated to varying extents but wide-spread radioactivity still remains. Fission and neutron-activation products at the test sites have been decaying over time but long-lived radioisotopes such as uranium and plutonium persist within the environment, predominantly in the form of discrete particles. These particles vary widely in composition depending upon the detonation characteristics and local geology, and are widely dispersed around each site. Radioactive particles are the dominant form of radionuclides at the former test sites and the future distribution of radioactive contaminants in the environment at these sites is largely dependent upon their fate and behaviour. The weathering of particles in the environment and the potential release of the radioactivity they contain is influenced by a range of factors including particle morphology, elemental composition and chemical form, and the prevailing environmental conditions. Radioactive particles have been isolated from soils and sediments from Australian test sites and characterised using photostimulated luminescence (PSL)-autoradiography, scanning electron microscopy energy dispersive X-ray spectroscopy (SEM-EDS), Synchrotron X-ray fluorescence microscopy (XFM) and particle-induced X-ray emission (PIXE). The characteristics of the particles and potential implications for their long term fate will be discussed in the context of the techniques applied and the environments in which the particles were found.
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    Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation
    (Springer Link, 2015-01) Callaghan, PD; Wimberley, CA; Rahardjo, GL; Berghofer, PJ; Pham, TQ; Jackson, TW; Zahra, D; Bourdier, T; Wyatt, N; Greguric, I; Howell, NR; Siegele, R; Pastuovic, Z; Mattner, F; Loc'h, C; Grégoire, MC; Katsifis, A
    The in vivo binding parameters of the novel imidazopyridine TSPO ligand [18F]PBR102 were assessed and compared with those of [18F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). Methods Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [18F]PBR102 or [18F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration–time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [125I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. Results The BPs of [18F]PBR102 [18F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [11C]PK11195. The presaturation study showed differences in the volume of distribution between the ipsilateral striatum and the striatum contralateral to the injury (0.7) indicating that an assumption of the SRTM was not met. The modelling indicated that the BPs were consistent for both ligands. Between the SRTM and 2TC model, the BPs were highly correlated, but there was a bias in BP. Conclusion [18F]PBR102 and [18F]PBR111 have equivalent binding properties in vivo, displaying significantly greater BPs with lower signal-to-noise ratio than [11C]PK11195. While an assumption of the SRTM was not met, this modelling approach was validated against 2TC modelling for both ligands, facilitating future use in longitudinal PET imaging of neuroinflammation.© 2014, Springer Nature
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    Development and validation of competition binding assays for affinity to the extracellular matrix receptors, αvβ3 and αIIbβ3 integrin
    (Elsevier B.V., 2012-04-01) Szabo, A; Howell, NR; Pellegrini, PA; Greguric, I; Katsifis, A
    The RGD (Arg-Gly-Asp) binding integrins αvβ3 and αIIbβ3 are integral components of various pathological and physiological processes, including tumor angiogenesis, osteoclast function, and thrombus formation. Because of this, there is interest in identifying novel compounds and proteins binding to these receptors as well as investigating the mechanism of these interactions. In this article, we describe the development and validation of competition binding assays for determining the affinity of test compounds to αvβ3 and αIIbβ3 integrin. Assays were successfully developed for each receptor, and the affinity of known compounds was comparable to published results. However, the inability of binding between αIIbβ3 integrin and the labeled echistatin protein ligand to reach equilibrium resulted in an assay that did not meet the assumptions of the competition binding model. Nevertheless, there was good agreement between this assay and known literature values, and intra- and interassay variability was acceptable. Binding by conformation-specific antibodies provided evidence that solid-phase bound αIIbβ3 receptor was in an activated conformation. This study also demonstrated that current models and methods for determining receptor affinity are simplistic and fail to account for common receptor–ligand interactions such as nondissociable interactions and varying receptor activation states. © 2012 by Elsevier Inc.
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    Gd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy
    (Australian National University, 2021-08-24) Middleton, RJ; Howell, NR; Livio, E; Wyatt, NA; Chacon, A; Fraser, BH; Barnes, M; Cameron, M; Rendina, LM; Häusermann, D; Lerch, M; Safavi-Naeini, M
    High-Z elements have been proposed as radiosensitisers in X-ray photon radiotherapy due to their emission of multiple high-LET photo- and Auger electrons following X-ray irradiation. Gadolinium is a particularly attractive candidate radiosensitiser, since it can also be used as an MRI contrast agent. In this study, we report on the efficacy of Gd-triphenylphosphonium salt-DOTA (Gd(III)-TPP-DOTA) for synchrotron microbeam radiation therapy dose enhancement. The compound utilises the mitochondrial targeting moiety triphenylphosphonium (TPP) to accumulate Gd in the inner mitochondrial membrane. Experiments were conducted using the dynamic mode option at hutch 2B of the Imaging and Medical Beamline at the Australian Synchrotron. Human glioblastoma multiforme cells (T98G cell line) were cultured to 80-90% confluence in T12.5 flasks. Approximately 24 hours prior to irradiation, the cultures were either treated with a 500 μM solution of Gd(III)DOTA-TPP or a vehicle control. Spatial dose distribution of synchrotron broad beam (BB) and single/multiple microbeams were measured using a micron-scale X-Tream dosimetry system and Gafchromic films in air and at 2 cm depth in solid water (same depth as the monolayer of cells in T12.5 flasks). A total of 96 flasks were irradiated, with doses of 0, 1, 2, 3, 4, 5, 10 and 16 Gy delivered in valley (MRT) or uniformly (BB). Post irradiation, each flask was re-seeded into 7 x 96 well-plates to perform the resazurin cell proliferation assay up to 7 days after irradiation. Our preliminary analysis indicates that for cells irradiated by 3 Gy of BB or MRT radiation, the addition of Gd(III)DOTA-TPP results in a reduction in viable cell mass by 24.25% and 25.79%, respectively, compared with untreated flasks. © The Authors
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    Initial data on adsorption of Cs and Sr to the surfaces of microplastics with biofilm
    (Elsevier, 2018-10) Johansen, MP; Prentice, E; Cresswell, T; Howell, NR
    The adsorption of radiocesium and radiostrontium onto a range of natural materials has been well quantified, but not for the new media of environmental plastics, which may have enhanced adsorption due to surface-weathering and development of biofilms. Microplastic samples were deployed in freshwater, estuarine and marine conditions, then characterised using infrared spectroscopy to document changes to the plastic surface (vs interior). Synchrotron elemental mapping data revealed surfaces that were well-covered by accumulation of reactive water solutes and sulphur, but, in contrast, had highly discrete coverage of elements such as Fe and Ti, indicating adhered mineral/clay-associated agglomerates that may increase overall adsorption capacity. Plastics that had been deployed for nearly five months adsorbed radionuclides in both freshwater and estuarine conditions with the highest Kd for cesium (Cs) in freshwater (80 ml g−1) and lowest for strontium (Sr) in estuarine conditions (5 ml g−1). The degree of Cs and Sr adsorption onto plastics appears to be approximately 2–3 orders of magnitude lower than for sediment reference values. While lower than for sediments, adsorption occurred on all samples and may indicate a significant radionuclide reservoir, given that plastics are relatively buoyant and mobile in water regimes, and are increasing in global aquatic systems. Crown Copyright © 2018 Published by Elsevier Ltd.
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    Investigating the foliar uptake of zinc from conventional and nano-formulations: a methodological study
    (CSIRO Publishing, 2019-06-06) Read, TL; Doolette, CL; Cresswell, T; Howell, NR; Aughterson, RD; Karatchevtseva, I; Donner, E; Kopittke, PM; Schjoerring, JK; Lombi, E
    Zinc (Zn) deficiency affects half of the world’s arable soil and one-third of the world’s human population. Application of Zn foliar fertilisers to cereal crops can be an effective way to increase grain Zn content; however, commonly used formulations can scorch the leaf (e.g. soluble Zn salts) or are prohibitively expensive (e.g. chelated Zn, ZnEDTA). Zinc oxide nanoparticles (ZnO-NPs) may offer an efficient and cost-effective alternative, but little is known regarding the mechanisms of Zn uptake and translocation within the plant. Foliar-applied Zn is analytically challenging to detect, locate and quantify, as it is omnipresent. Furthermore, any single analytical technique does not have the detection limit or spatial resolution required. In this study, the uptake and mobility of foliar-applied ZnEDTA, ZnO-NPs and ZnO microparticles (ZnO-MPs) to wheat (Triticum aestivum L.) were investigated using inductively coupled plasma mass spectroscopy (ICP-MS), synchrotron-based X-ray fluorescence microscopy (XFM) and radiotracing techniques using 65Zn-labelled formulations. The three techniques were compared to highlight limitations and advantages of each. We also report, for the first time, a novel time-resolved in vivo autoradiography imaging technique that can be used to visualise 65Zn in live plants treated with foliar applications of 65ZnO-NPs and MPs. The images were supplemented by gamma spectroscopy analysis for quantification. The results of this study provide important insights into the analytical challenges faced when investigating foliar-applied Zn nanofertilisers in plants. Potential solutions using nuclear techniques are also discussed, which in turn may ultimately lead to the development of more efficient foliar fertilisers. © CSIRO 2019
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    Investigation of elemental changes in brain tissues following excitotoxic injury
    (Elsevier, 2013-07-01) Siegele, R; Howell, NR; Callaghan, PD; Pastuovic, Z
    Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca+2 cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca+2 cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma. © 2013, Elsevier B.V.
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    Metabolism of CLINDE, a peripheral benzodiazepine receptor SPECT ligand
    (Springer, 2010-10-11) Peyronneau, MA; Mattner, F; Howell, NR; Jiang, C; Pelegrini, P; Greguric, I; Loc'h, C; Katsifis, A
    Aim: The iodinated imidazopyridine, N′, N′-diethyl-6-Chloro-(4′-[123I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([123I]CLINDE) has been characterized as a high affinity and selectivity ligand for SPECT imaging the peripheral benzodiazepine receptor (TSPO)1. As part of the development of this probe and for future investigations in humans, the metabolism of CLINDE was investigated in different species. The aim of this study was to identify the main metabolic pathways and the form(s) of cytochrome P450 (CYP) responsible for the biotransformation of this ligand. Materials and Methods: The in vitro metabolism of CLINDE and [123I]-CLINDE was carried out using rat and human liver microsomes as well as human recombinant CYP. Similar studies were performed in rat hepatocytes. Microsomalor hepatocyte incubations were analyzed by LC/MS and the structure of the metabolites characterized by MS-MS experiments. Results: In rat and human liver microsomes, CLINDE was converted to two main polar metabolites identified by LC/MS asN-dealkylated (m/z440)and hydroxylated metabolites (m/z484). In rat liver microsomes, the main metabolite resulted from hydroxylation of the ligand. In human liver microsomes, the metabolism of CLINDE was slower with major formation of anN-dealkyl metabolite. Microsomes from baculovirus-infected insect cells expressing human P450s isoforms (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18,2C19, 2D6, 2E1, 3A4, 3A5, SF9 control) were used to test their ability to catalyse the oxidation of CLINDE. CYP3A4 and CYP3A5 exhibited the highest catalytic activity for N-dealkylation, (3.3 and 3.8 nmol/nmolP450/min), followed byCYP2C19 (0.67 nmol/nmolP450/min) and CYP2D6 0.09 nmol/nmolP450/min). The other CYP isoforms did not form any detectable metabolites. For the hydroxylase activity relative to the formation of the molecular ion at m/z 484, CYP1A1 (4.05nmol/nmolP450/min), CYP1A2 (1.85 nmol/nmolP450/min) appeared to be the morecatalytically active, followed by CYP3A4 (0.95 nmol/nmolP450/min) and CYP2C19(0.42 nmol/nmolP450/min). The iodine atom was conserved in all the identified metabolites during the process of biotransformation. In rat hepatocytes, [123-I]-CLINDE was extensively and rapidly converted to at least five radiometabolites, the major metabolite being issued from methyl-hydroxylation. Conclusion: Cytochrome P450 catalysed in vitro studies of CLINDE, demonstrated the formation of N-dealkylated and hydroxylated metabolites. Species differences were observed in the rate of formation of rat and human metabolites. The above results suggest that CYP3A4 and CYP3A5 most markedly catalysed N-dealkylation of CLINDE while the hydroxylation was likely to depend more strongly on CYP1A isoforms (extrahepatic CYP1A1 and hepaticCYP1A2).
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    Microgravity × radiation: a space mechanobiology approach toward cardiovascular function and disease
    (Frontiers Media S.A., 2021-10-29) Basirun, C; Ferlazzo, ML; Howell, NR; Liu, GJ; Middleton, RJ; Martinac, B; Narayanan, SA; Poole, K; Gentile, C; Chou, J
    In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases. © 2021 Basirun, Ferlazzo, Howell, Liu, Middleton, Martinac, Narayanan, Poole, Gentile and Chou.
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    Mitochondrial translocator protein (TSPO) expression in the brain after whole body gamma irradiation
    (Frontier Media S.A., 2021-10-25) Betlazar, C; Middleton, RJ; Howell, NR; Storer, B; Davis, E; Davies, JB; Banati, RB; Liu, GJ
    The brain’s early response to low dose ionizing radiation, as may be encountered during diagnostic procedures and space exploration, is not yet fully characterized. In the brain parenchyma, the mitochondrial translocator protein (TSPO) is constitutively expressed at low levels by endothelial cells, and can therefore be used to assess the integrity of the brain’s vasculature. At the same time, the inducible expression of TSPO in activated microglia, the brain’s intrinsic immune cells, is a regularly observed early indicator of subtle or incipient brain pathology. Here, we explored the use of TSPO as a biomarker of brain tissue injury following whole body irradiation. Post-radiation responses were measured in C57BL/6 wild type (Tspo+/+) and TSPO knockout (Tspo–/–) mice 48 h after single whole body gamma irradiations with low doses 0, 0.01, and 0.1 Gy and a high dose of 2 Gy. Additionally, post-radiation responses of primary microglial cell cultures were measured at 1, 4, 24, and 48 h at an irradiation dose range of 0 Gy-2 Gy. TSPO mRNA and protein expression in the brain showed a decreased trend after 0.01 Gy relative to sham-irradiated controls, but remained unchanged after higher doses. Immunohistochemistry confirmed subtle decreases in TSPO expression after 0.01 Gy in vascular endothelial cells of the hippocampal region and in ependymal cells, with no detectable changes following higher doses. Cytokine concentrations in plasma after whole body irradiation showed differential changes in IL-6 and IL-10 with some variations between Tspo–/– and Tspo+/+ animals. The in vitro measurements of TSPO in primary microglial cell cultures showed a significant reduction 1 h after low dose irradiation (0.01 Gy). In summary, acute low and high doses of gamma irradiation up to 2 Gy reduced TSPO expression in the brain’s vascular compartment without de novo induction of TSPO expression in parenchymal microglia, while TSPO expression in directly irradiated, isolated, and thus highly activated microglia, too, was reduced after low dose irradiation. The potential link between TSPO, its role in mitochondrial energy metabolism and the selective radiation sensitivity, notably of cells with constitutive TSPO expression such as vascular endothelial cells, merits further exploration. © The Authors - Open Access
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    A new class of fluorinated 5-pyrrolidinylsulfonyl isatin caspase inhibitors for PET imaging of apoptosis
    (Royal Society of Chemistry, 2012-11-12) Krause-Heuer, AM; Howell, NR; Matesic, L; Dhand, G; Young, EL; Burgess, L; Jiang, CD; Lengkeek, NA; Fookes, CJR; Pham, TQ; Sobrio, F; Greguric, I; Fraser, BH
    Thirteen compounds in a new class of fluorinated 5-pyrrolidinylsulfonyl isatin derivatives were synthesised that have potent and selective inhibitory activity against effector caspases-3 and -7. With in vivo animal PET imaging studies of cerebral ischemia being planned, N-benzylation with selected para-substituted benzylic halides allowed systematic variation of lipophilicity (logP 1.94–3.31) without decreasing inhibition potency (IC50). From this series the p-methoxybenzyl analogue was selected for initial ‘proof-of-concept’ [18F]-fluoride radiolabelling which proceeded in good yield and purity with no need for a protection/deprotection strategy. © 2013 Royal Society of Chemistry
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    Optimisation of neodymium hydroxide micro-precipitation of polonium-210 for alpha spectrometry source preparation
    (South Pacific Environmental Radioactivity Association, 2022-11-29) Medley, P; Patterson, S; Howell, NR; Froehlich, MB
    Co-precipitation of actinides with lanthanide hydroxides is a suitable technique to prepare high resolution sources for alpha spectrometry. One such technique has been adapted and optimised for co-precipitation of 210Po with Nd(OH)3. Chemical recovery greater than 90%, with a resolution less than 40 keV at full-with-half-maximum (FWHM) was achieved. The method can be faster, less expensive and less labour intensive than routine techniques using auto-deposition of Po onto Ag. Owing to co-precipitation of several metals with Nd(OH)3, including Fe and alpha emitting radionuclides, radiochemical separation of 210Po from the sample matrix is required for this method to be effective. The technique, however, does effectively separate Po from Cu, and is thus highly suited to samples where complete radiochemical separation from Cu is difficult to achieve, such as copper concentrates. The method also achieves 94±2% separation of 210Po from Pb. A common technique for measurement of 210Pb uses an initial separation of 210Pb from 210Po and then allows time for ingrowth of 210Po. A second radiochemical separation is then performed for 210Po, measurement of which is used to infer the initial activity concentration of 210Pb. Effective separation of 210Po and 210Pb using Nd(OH)3 co-precipitation can therefore simultaneously radiochemically separate these two isotopes and prepare 210Po for alpha spectrometry. Thus, reducing radiochemical processing for 210Pb analysis when measured through ingrowth of 210Po. As Bi is also co-precipitated with Nd(OH)3 with this method, a correction factor for contribution from 210Bi to the 210Po activity measured may be required. Biological samples were processed using microwave-assisted digestion followed by radiochemical separation for 210Pb and 210Po. Co-precipitation of 210Po with Nd(OH)3 was done on the 210Po fraction from both separated fractions, a delay after radiochemical separation for the 210Pb fraction was allowed for ingrowth of 210Po. Results from these measurements will be presented.
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    Plutonium and other radionuclides persist across marine-to-terrestrial ecotopes in the Montebello Islands sixty years after nuclear tests
    (Elsevier, 2019-11-15) Johansen, MP; Child, DP; Cresswell, T; Harrison, JJ; Hotchkis, MAC; Howell, NR; Johansen, A; Sdraulig, S; Thiruvoth, S; Young, EL; Whiting, SD
    Since the 1956 completion of nuclear testing at the Montebello Islands, Western Australia, this remote uninhabited island group has been relatively undisturbed (no major remediations) and currently functions as high-value marine and terrestrial habitat within the Montebello/Barrow Islands Marine Conservation Reserves. The former weapons testing sites, therefore, provide a unique opportunity for assessing the fate and behaviour of Anthropocene radionuclides subjected to natural processes across a range of shallow-marine to island-terrestrial ecological units (ecotopes). We collected soil, sediment and biota samples and analysed their radionuclide content using gamma and alpha spectrometry, photostimulated luminescence autoradiography and accelerator mass spectrometry. We found the activity levels of the fission and neutron-activation products have decreased by ~hundred-fold near the ground zero locations. However, Pu concentrations remain elevated, some of which are high relative to most other Australian and international sites (up to 25,050 Bq kg−1 of 239+240+241Pu). Across ecotopes, Pu ranked from highest to lowest in the following order: island soils > dunes > foredunes > marine sediments > and beach intertidal zone. Low values of Pu and other radionuclides were detected in all local wildlife tested including endangered species. Activity concentrations ranked (highest to lowest) terrestrial arthropods > terrestrial mammal and reptile bones > algae > oyster flesh > whole crab > sea turtle bone > stingray and teleost fish livers > sea cucumber flesh > sea turtle skin > teleost fish muscle. The three detonations (one from within a ship and two from 30 m towers) resulted in differing contaminant forms, with the ship detonation producing the highest activity concentrations and finer more inhalable particulate forms. The three sites are distinct in their 240/239Pu and 241/239Pu atom ratios, including the Pu transported by natural process or within migratory living organisms. Crown Copyright © 2019 Published by Elsevier B.V
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    Positron emission tomography and functional characterization of a complete PBR/TSPO knockout
    (Springer Nature, 2014-11-19) Banati, RB; Middleton, RJ; Chan, RHY; Hatty, CR; Wai-Ying Kam, W; Quin, C; Graeber, MB; Parmar, A; Zahra, D; Callaghan, PD; Fok, S; Howell, NR; Grégoire, MC; Szabo, A; Pham, TQ; Davis, E; Liu, GJ
    The evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer’s disease to anxiety. Here we show that global C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from GuwiyangWurraTSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of GuwiyangWurraTSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs. Copyright © 2014, Springer Nature
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    Radioactive particles from a range of past nuclear events: challenges posed by highly varied structure and composition
    (Elsevier B. V., 2022-10-10) Johansen, MP; Child, DP; Collins, RN; Cook, M; Howell, NR; Ikeda-Ohno, A; Young, EL
    While they have appeared only recently in earth's history, radioactive particles from anthropogenic sources are widespread in global environments and present radiological harm potentials to living organisms. Exposure potentials vary greatly, however few studies examine a wide range of source and particle types. Here we compare a varied set of particles from past nuclear fission and non-fission sources in Australia of highly diverse magnitudes, release modes, and environments. The radiochemistry and microscopy methods revealed that numerous radioactive particles persist in soils 60+ years after their release events. Particles can be distinguished by their Ca/Fe and Si/Fe elemental ratios, which in this study range over orders of magnitude and reflect the materials available during their individual formation events. The particles with Si- and Ca-dominant compositions persisted in corrosive environments (e.g., marine). Internal fracturing is more prevalent than previously reported, and fracturing is greater in Ca-rich vs. Si-dominated matrices. The fractures often form connective pathways from the interior to exterior surfaces, increasing the potential to leach radionuclides into a host organism or the environment. The particles from nuclear testing have dominant 239+240Pu activity concentrations, relative to 90Sr and 137Cs, which increases long-term radiological hazard from alpha emissions if inhaled or ingested, and contrasts with particles from nuclear power accidents (e.g., Fukushima). Additional physical/chemical/radiological measurements are needed to fully understand long-term fate and hazard potentials. Crown Copyright © 2022 Published by Elsevier B.V.
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    Recent survey of plutonium at the Montebello Islands nuclear test sites: uptake in marine and terrestrial organisms in a radioactive-particle environment
    (South Pacific Environmental Radioactivity Association, 2018-11-06) Johansen, MP; Child, DP; Cresswell, T; Harrison, JJ; Hotchkis, MAC; Howell, NR; Thiruvoth, S; Young, EL; Sdraulig, S; Whiting, SD
    The plutonium (Pu) residues from the former nuclear weapons tests at the Montebello Islands, Australia, provide unique opportunities for radioecological science. The area has important ecological and conservation values and supports marine and terrestrial threatened species. Local fallout from the l95Os tests left a legacy of fission products and actinides, often in the form of radioactive particles. Plutonium is penvasive and persistent at the sites. Of the nuclear test residues, it remains the primary exposure hazard to wildlife, human visitors and researchers. The highest totalPu measurement in soil found by our limited 2015 sampling (25,050 Bd kg-1) is well above post-cleanup levels at Maralinga and international benchmarks (e.g. the 100 Bq kg-1 IAEA benchmark for the release of material to the public). Other residual radionuclides are present and generally rank (highest-to-lowest activity concentrations): totalPu > 137Cs > 90Sr > 241Am > 152Eu > totalU > 230Th > 60Co although some local variation exists. Across ecological zones, radionuclide levels generally rank: island soils > dunes > beach above high tide (turtle nesting zones) > sea sediments > and intertidal zone. The intertidal beach is the least contaminated zone as many of the radionuclides have been washed into the nearby waters and sea sediments by daily waves as well as frequent storms. However, higher activity concentrations occur below the surface sands, with the maximum occurring at ~1 m at Burgundy Bay beach near the Mosaic G2 test site. At the ground-zero areas, gamma dose rates have reduced by about lOO-fold since 1962 due to the depletion of short-lived neutron activation products. The gamma emissions are easily detected by hand-held devices. Away from these areas, the Pu, in particular, is persistent but is not readily detectable in the field. The use of hand-held detectors or radiation badges alone does not effectively detect the Pu, 90Sr, and other key radionuclides, and therefore may provide a false sense of security to researchers and island visitors. Radionuclide activity concentrations were measured for representative ecological organisms including: algae, oysters, sea cucumbers, crabs, stingrays, fish, and sea turtles. The Pu isotopic signatures from the three tests are distinct from each other, and from world-wide fallout. These signatures could aid in determining local vs regional occupancy and may be useful, along with stable isotopes and other markers, in migration and habitat usage studies for turtles and other species.