ORCID Profile
0000-0002-5549-6459
Current Organisation
University of Western Australia
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Publisher: American Society of Hematology
Date: 09-2005
DOI: 10.1182/BLOOD-2004-08-3049
Abstract: The balance between pro- and anti-inflammatory cytokines modulates inflammation. Intracellular inhibitors of signaling, in turn, contribute to the negative regulation of cytokines. One of these inhibitors is suppressor of cytokine signaling-1 (SOCS-1). Socs1-/- mice die by 3 weeks of age with inflammation and fatty necrosis of the liver. Here, cre/loxP deletion of Socs1 was used to investigate the contribution of specific cells/tissues to inflammatory disease. Mice with SOCS-1 deficiency in myeloid and lymphoid cells, but not lymphoid alone, became ill at 50 to 250 days of age. These mice developed splenomegaly and T-cell/macrophage infiltration of many organs, including liver, lung, pancreas, and muscle. There were also abnormally high levels of the proinflammatory cytokines interferon γ (IFN-γ), tumor necrosis factor (TNF), and interleukin-12 (IL-12), and activated T cells circulating in these mice. Socs1null T cells were found to be hypersensitive to multiple cytokines, including IL-1, IL-2, and IL-12, resulting in IFN-γ production without requiring T-cell receptor (TCR) ligation. Additionally, Socs1null macrophages produced excessive amounts of IL-12 and TNF in response to other cytokines, including IFN-γ. A dysregulated cytokine network between T cells and macrophages is thus associated with this inflammatory disease. These findings indicate that SOCS-1 is critical in both T cells and macrophages for preventing uncontrolled inflammation. (Blood. 2005 :1668-1675)
Publisher: Oxford University Press (OUP)
Date: 23-02-2017
DOI: 10.1002/STEM.2567
Abstract: Developmental stage-specific differentiation of stem or progenitor cells into safe and functional cells is of fundamental importance in regenerative medicine, including β-cell replacement. However, the differentiation of islet progenitor cells (IPCs) into insulin-secreting β cells remains elusive. Here, we report that the multifunctional molecule nicotinamide (NIC) is a specific differentiation regulator of mouse IPCs. The differentiated cells regulated by NIC exhibited many characteristics of adult β cells, including ameliorating preclinical diabetes and a highly comparable transcriptome profile. Gene set enrichment analysis showed that during differentiation, numerous IPC transcription factor genes, including Ngn3, Pax4, Fev, and Mycl1, were all down regulated. Pharmacological, biochemical, and gene knockdown analyses collectively demonstrated that NIC regulated the differentiation via inhibiting Sirt1 (silent information regulator transcript 1). Finally, NIC also regulates human IPC differentiation. Thus, our study advances islet developmental biology and impacts on translational research and regenerative therapies to diabetes and other diseases.
Publisher: Elsevier BV
Date: 09-2005
Publisher: Elsevier BV
Date: 11-2017
Publisher: American Vacuum Society
Date: 14-06-2022
DOI: 10.1116/6.0001623
Abstract: Given the recent increase in the demand for gallium nitride (GaN) in different markets like optoelectronics and power devices, the request for epitaxially grown GaN will further increase. To meet this high demand, higher throughput and more economical manufacturing technologies must be advanced. In this work, GaN thin films are deposited by reactive sputter deposition from a liquid gallium target at a substrate temperature of 900 °C. The layers are grown epitaxially on c-plane oriented sapphire in an industrial-scale sputter tool from Evatec AG. Due to the growth rate of & nm/s and the fast substrate heat-up time, the throughput in a production setup can be increased compared to other GaN growth techniques. The resistivity of the intrinsic insulating GaN can be lowered by intentional Si doping during the sputter deposition process by three orders of magnitude. Thereby, conductive n-type GaN can be grown with different dopant amounts. The carrier mobility of the sputter deposited film is 45 cm2 V−1 s−1 at a carrier concentration of 1.1 × 1020 cm−3 based on room temperature Hall measurements using a van der Pauw geometry. The lowest resistivity reaches 1300 μΩ cm, which is confirmed by sheet resistance measurements. Undoped films exhibit an x-ray diffraction rocking curve full width at half maximum of 0.2°, which increases up to 0.5° for highly Si-doped layers. The presented results show that GaN prepared by reactive sputter deposition from a liquid gallium source is a viable alternative to conventional deposition techniques for GaN.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2017
DOI: 10.1007/S11095-017-2138-Y
Abstract: Recently we demonstrated that microencapsulation of a murine pancreatic β-cell line using an alginate-ursodeoxycholic acid (UDCA) matrix produced microcapsules with good stability and cell viability. In this study, we investigated if translation of this formulation to microencapsulation of primary β-cells harvested from mature double-transgenic healthy mice would also generate stable microcapsules with good cell viability. Islets of Langerhans were isolated from Ngn3-GFP/RIP-DsRED mice by intraductal collagenase P digestion and density gradient centrifugation, dissociated into single cells and the β-cell population purified by Fluorescence Activated Cell Sorting. β-cells were microencapsulated using either alginate-poly-l-ornithine (F1 control) or alginate-poly-l-ornithine-UDCA (F2 test) formulations. Microcapsules were microscopically examined and microencapsulated cells were analyzed for viability, insulin and cytokine release, 2 days post-microencapsulation. Microcapsules showed good uniformity and morphological characteristics and even cell distribution within microcapsules with or without UDCA. Two days post microencapsulation cell viability, mitochondrial ATP and insulin production were shown to be optimized in the presence of UDCA whilst production of the proinflammatory cytokine IL-1β was reduced. Contradictory to our previous studies, UDCA did not reduce production of any other pro-inflammatory biomarkers. These results suggest that UDCA incorporation improves microcapsules' physical and morphological characteristics and improves the viability and function of encapsulated mature primary pancreatic β-cells.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.PCD.2021.09.011
Abstract: To improve perinatal outcomes, screening for hyperglycaemia using 75 g oral glucose tolerance test (OGTT) is recommended for all pregnant women at 24-28 weeks gestation (routine), and earlier if high-risk. Screening coverage for remote and Aboriginal Australian women is less than ideal. This study examined OGTT completion (early and routine) by women from rural and remote Western Australia compared with early glycated haemoglobin (HbA In 2015-2018, 27 primary health care sites recruited 600 (233 Aboriginal) women aged ≥16-years, without pre-existing diabetes, who delivered >30-weeks gestation. All women presenting <20-weeks gestation (541) were offered an early study HbA HbA Universal early pregnancy HbA
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-09-2021
Abstract: A variant in an RNA processing enzyme predisposes to insulin resistance by reducing calcium release and insulin secretion.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 03-10-2018
Publisher: American Chemical Society (ACS)
Date: 17-07-2017
DOI: 10.1021/ACS.MOLPHARMACEUT.7B00220
Abstract: In previous studies, we developed a new technique (ionic gelation vibrational jet flow IGVJF) in order to encapsulate pancreatic β-cells, for insulin in vivo delivery, and diabetes treatment. The fabricated microcapsules showed good morphology but limited cell functions. Thus, this study aimed to optimize the IGVJF technique, by utilizing integrated electrode tension, coupled with high internal vibration, jet-flow polymer stream rate, ionic bath-gelation concentrations, and gelation time stay. The study also utilized double inner/outer nozzle segmented-ingredient flow of microencapsulating dispersion, in order to form β-cell microcapsules. Furthermore, a microcapsule-stabilizing bile acid was added, and microcapsule's stability and cell functions measured. Buchi-based built-in system utilizing IGVJF technology was screened to produce best microcapsule-containing β-cells with or without a stabilizing-enhancing bile acid. Formed microcapsules were examined, for physical characteristics, and encapsulated cells were examined for survival, insulin release, and inflammatory profiles. Optimized microencapsulating parameters, using IGJVF, were: 1000 V voltage, 2500 Hz frequency, 1 mL/min flow rate, 3% w/v ionic-bath gelation concentration, and 20 min gelation time. Microcapsules showed good morphology and stability, and the encapsulated cells showed good survival, and insulin secretion, which was optimized by the bile acid. Deployed IGVJF-based microencapsulating parameters utilizing stability-enhancing bile acid produced best microcapsules with best pancreatic β-cells functions and survival rate, which, suggests potential application in cell transplantation.
Publisher: Future Science Ltd
Date: 10-2017
Abstract: Aim: A semisynthetic primary bile acid (PBA) has exerted hypoglycemic effects in Type 1 diabetic animals, which were hypothesized to be due to its anti-inflammatory and cellular glucose-regulatory effects. Thus, the research purpose aimed to examine antidiabetic effects of a PBA, in terms of cellular inflammation and survival and insulin release, in the context of supporting β-cell delivery and Type 1 diabetic treatment. Materials & methods: 10 formulations were prepared, five without PBA (control) and five with PBA (test). Formulations were used to microencapsulate pancreatic β cells and the microcapsules were examined for morphology, cell viability, insulin release and inflammation. Results & conclusion: PBA improved cell viability, insulin release and reduced inflammation in a formulation-dependent manner, which suggests potential use in cell delivery and diabetes treatment. [Formula: see text]
Publisher: MDPI AG
Date: 14-11-2019
Abstract: Gestational diabetes mellitus (GDM) is the most common antenatal complication in Australia. All pregnant women are recommended for screening by 75 g oral glucose tolerance test (OGTT). As part of a study to improve screening, 694 women from 27 regional, rural and remote clinics were recruited from 2015–2018 into the Optimisation of Rural Clinical and Haematological Indicators for Diabetes in pregnancy (ORCHID) study. Most routine OGTT s les were analysed more than four hours post fasting collection (median 5.0 h, range 2.3 to 124 h), potentially reducing glucose levels due to glycolysis. In 2019, to assess pre-analytical plasma glucose (PG) instability over time, we evaluated alternative s le handling protocols in a s le of participants. Four extra s les were collected alongside routine room temperature (RT) fluoride-oxalate s les (FLOXRT): study FLOXRT ice slurry (FLOXICE) RT fluoride-citrate-EDTA (FC Mix), and RT lithium-heparin plasma separation tubes (PST). Time course glucose measurements were then used to estimate glycolysis from ORCHID participants who completed routine OGTT after 24 weeks gestation (n = 501). Adjusting for glycolysis using FLOXICE measurements estimated 62% under-diagnosis of GDM (FLOXRT 10.8% v FLOXICE 28.5% (95% CI, 20.8–29.5%), p 0.001). FC Mix tubes provided excellent glucose stability but gave slightly higher results (Fasting PG: +0.20 ± 0.05 mmol/L). While providing a realistic alternative to the impractical FLOXICE protocol, direct substitution of FC Mix tubes in clinical practice may require revision of GDM diagnostic thresholds.
Publisher: Elsevier BV
Date: 05-2023
DOI: 10.1016/J.CLINBIOCHEM.2022.10.002
Abstract: To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT s les with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a erse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT s les at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to in idual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.
Publisher: American Diabetes Association
Date: 09-11-2021
DOI: 10.2337/DC20-2211
Publisher: American Diabetes Association
Date: 03-12-2009
DOI: 10.2337/DB09-1151
Abstract: High concentrations of circulating glucose are believed to contribute to defective insulin secretion and β-cell function in diabetes and at least some of this effect appears to be caused by glucose-induced β-cell apoptosis. In mammalian cells, apoptotic cell death is controlled by the interplay of proapoptotic and antiapoptotic members of the Bcl-2 family. We investigated the apoptotic pathway induced in mouse pancreatic islet cells after exposure to high concentrations of the reducing sugars ribose and glucose as a model of β-cell death due to long-term metabolic stress. Islets isolated from mice lacking molecules implicated in cell death pathways were exposed to high concentrations of glucose or ribose. Apoptosis was measured by analysis of DNA fragmentation and release of mitochondrial cytochrome c. Deficiency of interleukin-1 receptors or Fas did not diminish apoptosis, making involvement of inflammatory cytokine receptor or death receptor signaling in glucose-induced apoptosis unlikely. In contrast, overexpression of the prosurvival protein Bcl-2 or deficiency of the apoptosis initiating BH3-only proteins Bim or Puma, or the downstream apoptosis effector Bax, markedly reduced glucose- or ribose-induced killing of islets. Loss of other BH3-only proteins Bid or Noxa, or the Bax-related effector Bak, had no impact on glucose-induced apoptosis. These results implicate the Bcl-2 regulated apoptotic pathway in glucose-induced islet cell killing and indicate points in the pathway at which interventional strategies can be designed.
Publisher: Wiley
Date: 23-01-2016
DOI: 10.1002/BTPR.2223
Abstract: Recently sodium alginate (SA)-poly-l-ornithine (PLO) microcapsules containing pancreatic β-cells that showed good morphology but low cell viability (<27%) was designed. In this study, two new polyelectrolytes, polystyrenic sulfonate (PSS at 1%) and polyallylamine (PAA at 2%) were incorporated into a microencapsulated-formulation, with the aim of enhancing the physical properties of the microcapsules. Following incorporation, the structural characteristics and cell viability were investigated. The effects of the anti-inflammatory bile acid, ursodeoxycholic acid (UDCA), on microcapsule morphology, size, and stability as well as β-cell biological functionality was also examined. Microcapsules were prepared using PLO-PSS-PAA-SA mixture and two types of microcapsules were produced: without UDCA (control) and with UDCA (test). Microcapsule morphology, stability, and size were examined. Cell count, microencapsulation efficiency, cell bioenergetics, and activity were also examined. The new microcapsules showed good morphology but cell viability remained low (29% ± 3%). UDCA addition improved cell viability post-microencapsulation (42 ± 5, P < 0.01), reduced swelling (P < 0.01), improved mechanical strength (P < 0.01), increased Zeta-potential (P < 0.01), and improved stability. UDCA addition also increased insulin production (P < 0.01), bioenergetics (P < 0.01), and decreased β-cell TNF-α (P < 0.01), IFN-gamma (P < 0.01), and IL-6 (P < 0.01) secretions. Addition of 4% UDCA to a formulation system consisting of 1.8% SA, 1% PLO, 1% PSS, and 2% PAA enhanced cell viability post-microencapsulation and resulted in a more stable formulation with enhanced encapsulated β-cell metabolism, bioenergetics, and biological activity with reduced inflammation. This suggests potential application of UDCA, when combined with SA, PLO, PSS, and PAA, in β-cell microencapsulation and diabetes treatment. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:501-509, 2016.
Publisher: Informa UK Limited
Date: 04-08-2018
DOI: 10.1080/21691401.2017.1362416
Abstract: Current trials for β-cell transplantation have been hindered by poor cell viability and function post-transplantation. Recently, electric charges of the microencapsulating formulation carrying β-cells have shown significant effects on cell survival and function. Thus, this study aimed at investigating the effects of electric charge, of novel colloidal formulation containing β-cells, on cell viability, biological activity and insulin release. A new formulation, containing high ratios of poly-L-ornithine, suspending electrical-stimulation hydrogel and polystyrene sulphone (1:1:0.1 ratio), was used to form microcapsules utilizing 800 V and 2000 Hz encapsulating conditions. The bile acid, ursodeoxycholic acid, was added into the microcapsules to measure its effects on electric charges. The electric charge of the microencapsulating formulation was enhanced by bile acid addition, and resulted in better cell viability and function. Ursodeoxycholic acid microencapsulated with poly-L-ornithine, suspending electrical-stimulation hydrogel and polystyrene sulphone at 1:1:0.1 ratio, using 800 V and 2000 Hz microencapsulating conditions, produced enhanced electrokinetic parameters of microcapsules with optimized cell functions. This suggests that electric charge of formulations containing pancreatic β-cell may have significant effects on cell mass and functions, post-transplantation.
Publisher: Informa UK Limited
Date: 09-05-2018
DOI: 10.1080/10837450.2017.1321664
Abstract: Ideal cell-containing microcapsules should be capable of maintaining cell viability and exhibit significant structural stability to support cellular functionality. To date, such microcapsules remain unavailable thus, this study used our well-established microencapsulating methods to examine a total of 32 different microencapsulating formulations and correlate polymers' molecular weights (M MIN6 mouse-cloned pancreatic β-cells were microencapsulated using control (n = 16 without UDCA) and test (n = 16 with UDCA) different polymers. Confocal microscopic imaging, cell viability, and microcapsules' stability were assessed. Best cell viability (>50%) was obtained at average M UDCA addition improved microenvironmental conditions within the microcapsules but this effect was largely dependent on the polymer systems used.
Publisher: CSIRO Publishing
Date: 2017
DOI: 10.1071/AH16125
Abstract: Objective Government expenditure on and the number of aged care facilities in Australia have increased consistently since 1995. As a result, a range of aged care policy changes have been implemented. Data on demographics and utilisation are important in determining the effects of policy on residential aged care services. Yet, there are surprisingly few statistical summaries in the peer-reviewed literature on the profile of Australian aged care residents or trends in service utilisation. Therefore, the aim of the present study was to characterise the demographic profile and utilisation of a large cohort of residential aged care residents, including trends over a 3-year period. Methods We collected 3 years of data (2011–14) from 77 residential aged care facilities and assessed trends and differences across five demographic and three service utilisation variables. Results The median age at admission over the 3-year period remained constant at 86 years. There were statistically significant decreases in separations to home (z = 2.62, P = 0.009) and a 1.35% increase in low care admissions. Widowed females made up the majority (44.75%) of permanent residents, were the oldest and had the longest lengths of stay. One-third of permanent residents had resided in aged care for 3 years or longer. Approximately 30% of residents were not born in Australia. Aboriginal residents made up less than 1% of the studied population, were younger and had shorter stays than non-Aboriginal residents. Conclusion The analyses revealed a clear demographic profile and consistent pattern of utilisation of aged care facilities. There have been several changes in aged care policy over the decades. The analyses outlined herein illustrate how community, health services and public health data can be used to inform policy, monitor progress and assess whether intended policy has had the desired effects on aged care services. What is known about the topic? Characterisation of permanent residents and their utilisation of residential aged care facilities is poorly described in the peer-reviewed literature. Further, publicly available government reports are incomplete or characterised using incomplete methods. What does this paper add? The analyses in the present study revealed a clear demographic profile and consistent pattern of utilisation of aged care facilities. The most significant finding of the study is that one-third of permanent residents had resided in an aged care facility for ≥3 years. These findings add to the overall picture of residential aged care utilisation in Australia. What are the implications for practitioners? The analyses outlined herein illustrate how community, health services and public health data can be utilised to inform policy, monitor progress and assess whether or not intended policy has had the desired effects on aged care services.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2016
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 19-12-2006
DOI: 10.1111/J.1440-1711.2005.01397.X
Abstract: Pro-inflammatory cytokines have been implicated in the death of pancreatic beta cells leading to type 1 diabetes. NIT-1 cells are an insulinoma cell line derived from mice expressing the SV40 large T antigen. These cells are a useful tool in analysis of beta cell death. NIT-1 cells are highly susceptible to caspase-dependent apoptosis induced by TNF-alpha alone. Primary islets are not susceptible to cell death induced by TNF-alpha alone however, they are killed by TNF-alpha and IFN-gamma in a nitric oxide-dependent manner. We examined signal transduction in NIT-1 cells in response to cytokines to determine the mechanism for TNF-alpha-induced apoptosis. We found that NIT-1 cells are defective in the activation of nuclear factor-kappaB (NFkappaB) as a result of functionally deficient RelA activity, because overexpression of RelA protected NIT-1 cells from apoptosis. TNF-alpha also did not induce phosphorylation of c-Jun N-terminal kinase in NIT-1 cells. Together, these defects prevent expression of anti-apoptotic genes in NIT-1 cells and make them susceptible to TNF-alpha. To determine whether similar defects in primary beta cells would induce the same effect, we examined TNF-alpha-induced apoptosis in islets isolated from mice deficient in NFkappaB p50. These islets were as susceptible as wild-type islets to TNF-alpha and IFN-gamma-induced cell death. In contrast to wild-type islets, cell death was not prevented by inhibition of nitric oxide in p50-deficient islets. Blocking NFkappaB has been proposed as a mechanism for protection of beta cells from cytokine-induced cell death in vivo. Our results suggest that this would make beta cells equally or more sensitive to cytokines.
No related grants have been discovered for Emma Jamieson.