ORCID Profile
0000-0002-7499-789X
Current Organisation
University of South Australia
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Publisher: Oxford University Press (OUP)
Date: 28-04-2022
DOI: 10.1093/BFGP/ELAC006
Abstract: Preecl sia is a pregnancy-specific disease that can have serious effects on the health of both mothers and their offspring. Predicting which women will develop preecl sia in early pregnancy with high accuracy will allow for improved management. The clinical symptoms of preecl sia are well recognized, however, the precise molecular mechanisms leading to the disorder are poorly understood. This is compounded by the heterogeneous nature of preecl sia onset, timing and severity. Indeed a multitude of poorly defined causes including genetic components implicates etiologic factors, such as immune maladaptation, placental ischemia and increased oxidative stress. Large datasets generated by microarray and next-generation sequencing have enabled the comprehensive study of preecl sia at the molecular level. However, computational approaches to simultaneously analyze the preecl sia transcriptomic and network data and identify clinically relevant information are currently limited. In this paper, we proposed a control theory method to identify potential preecl sia-associated genes based on both transcriptomic and network data. First, we built a preecl sia gene regulatory network and analyzed its controllability. We then defined two types of critical preecl sia-associated genes that play important roles in the constructed preecl sia-specific network. Benchmarking against differential expression, betweenness centrality and hub analysis we demonstrated that the proposed method may offer novel insights compared with other standard approaches. Next, we investigated subtype specific genes for early and late onset preecl sia. This control theory approach could contribute to a further understanding of the molecular mechanisms contributing to preecl sia.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2NR05619D
Abstract: Magnetic extracellular vesicle (EV) enrichment using antibody conjugated bacteria-derived iron oxide nanowires coupled with mass spectrometry-based proteome profiling enables efficient EV subtype enrichment and reproducible proteomics.
Publisher: American Chemical Society (ACS)
Date: 04-09-2019
DOI: 10.1021/ACS.ANALCHEM.9B03559
Abstract: Potentiometric sensors based on silicon nanowire field effect transistors (SiNW FETs) typically display exquisite sensitivities, but their bioanalytical implementation is limited due to the need for stringent measurement conditions and high-precision readout units. An alternative operation principle where SiNW FETs are operated in a frequency-domain electrical impedimetric approach is promising. However, to date only limited data is available in regard to the sensing performance and translational relevance of this novel approach in comparison to the standard charge detection paradigm. We demonstrate the feasibility of conducting electrical impedimetric FET measurements with a portable unit for the ultrasensitive detection of cancer biomarkers in biospecimens. Compared to standard potentiometric measurements, electrical impedimetric FET measurements yielded significant improvements in biosensing performances, including the limit of detection, sensing resolution, and dynamic range.
Publisher: Wiley
Date: 14-06-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NR02461B
Abstract: We first present and pilot clinically validate a fully integrated, high-performance indium oxide nano-transistor biodiagnostic platform for rapid, accurate testing of preecl sia without analytical equipment aids and minimum operator intervention.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.TIBTECH.2021.10.011
Abstract: Technological advances in bioengineering, especially in microphysiological systems and organoids, are changing the way in which placental tissue is used and perceived. These advances raise important questions surrounding consent, privacy, biobanking, and research ethics. We explore emerging technologies which use placental tissue and the pressing associated bioethical concerns they raise.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2018
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.BIOMATERIALS.2014.04.047
Abstract: Multicellular tumour spheroids closely recapitulate the physiological environment of tumour tissues. However, their implementation in drug screening assays remains limited due to the technological challenges of forming large numbers of high quality spheroids in platforms compatible with high throughput screening. A simple bench-top microfabrication strategy is demonstrated here based on the principle of ice lithography carried out on superhydrophobic substrates to fabricate quasi-spherical microwells (spheriwells). The microwells shapes and dimensions are directly controlled by the hydrophobicity of the substrate and the volume of the water droplets. The prepared concave microwells enable the formation of dense and homogeneous multicellular tumour spheroids. Spheroids formed within spheriwells are trapped within the microwells, which eliminate loss during media manipulation and facilitate long-term on-chip culture. Morphological and phenotypical changes associated with the growth of MCF-7 adenocarcinoma cells in spheriwells were characterised using imaging flow cytometry and revealed the appearance of heterogeneous populations with loss of E-Cadherin expression. The compatibility of the spheriwells with an on-chip MTT assay is demonstrated. The very unusual shape of the spheriwells, prepared using materials and methods routinely used in most research laboratories, provides a straightforward and scalable platform to prepare high quality multicellular tumour spheroids compatible with high throughput biological screening assays.
Publisher: Bioscientifica
Date: 10-2022
DOI: 10.1530/REP-21-0428
Abstract: There is a pregnancy-induced vasodilation of blood vessels, which is known to have a protective effect on cardiovascular function and can be maintained postpartum. This review outlines the cardiovascular changes that occur in a healthy human and rodent pregnancy, as well as different pathways that are activated by angiotensin II and relaxin that result in blood vessel dilation. During pregnancy, systemic and uteroplacental blood flow increase to ensure an adequate blood supply that carries oxygen and nutrients from the mother to the fetus. This results in changes to the function of the maternal cardiovascular system. There is also a pregnancy-induced vasodilation of blood vessels, which is known to have a protective effect on cardiovascular health/function. Additionally, there is evidence that the effects of maternal vascular vasodilation are maintained post-partum, which may reduce the risk of developing high blood pressure in the next pregnancy and reduce cardiovascular risk later in life. At both non-pregnant and pregnant stages, vascular endothelial cells produce a number of vasodilators and vasoconstrictors, which transduce signals to the contractile vascular smooth muscle cells to control the dilation and constriction of blood vessels. These vascular cells are also targets of other vasoactive factors, including angiotensin II (Ang II) and relaxin. The binding of Ang II to its receptors activates different pathways to regulate the blood vessel vasoconstriction/vasodilation, and relaxin can interact with some of these pathways to induce vasodilation. Based on the available literature, this review outlines the cardiovascular changes that occur in a healthy human pregnancy, supplemented by studies in rodents. A specific focus is placed on vasodilation of blood vessels during pregnancy the role of endothelial cells and endothelium-derived vasodilators will also be discussed. Additionally, different pathways that are activated by Ang II and relaxin that result in blood vessel dilation will also be reviewed.
Publisher: MDPI AG
Date: 26-09-2019
Abstract: The presence or absence of tumor cells within patient lymph nodes is an important prognostic indicator in a number of cancer types and an essential element of the staging process. However, patients with the same pathological stage will not necessarily have the same outcome. Therefore, additional factors may aid in identifying patients at a greater risk of developing metastasis. In this proof of principle study, initially, spiked tumor cells in rat lymph nodes were used to mimic a node with a small cancer deposit. Next, human lymph nodes were obtained from cancer patients for morphological characterization. Nodes were dissociated with a manual tissue homogenizer and stained with fluorescent antibodies against CD45 and Pan-Cytokeratin and then imaging flow cytometry (AMNIS ImageStreamX Mark II) was performed. We show here that imaging flow cytometry can be used for the detection and characterization of small numbers of cancer cells in lymph nodes and we also demonstrate the phenotypical and morphological characterization of cancer cells in gastrointestinal cancer patient lymph nodes. When used in addition to conventional histological techniques, this high throughput detection of tumor cells in lymph nodes may offer additional information assisting in the staging process with therapeutic and prognostic applications.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.TIBTECH.2021.03.009
Abstract: Driven by a lack of appropriate human placenta models, recent years have seen the introduction of bioengineered in vitro models to better understand placental health and disease. Thus far, the focus has been on the maternal-foetal barrier. However, there are many other physiologically and pathologically significant aspects of the placenta that would benefit from state-of-the-art bioengineered models, in particular, integrating advanced culture systems with contemporary biological concepts such as organoids. This critical review defines and discusses the key parameters required for the development of physiologically relevant in vitro models of the placenta. Specifically, it highlights the importance of cell type, mechanical forces, and culture microenvironment towards the use of physiologically relevant models to improve the understanding of human placental function and dysfunction.
Publisher: Elsevier BV
Date: 2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4AN01768D
Abstract: Depletion of .7% WBCs enabling tumor cell recovery from blood with nano-rough PDMS microfluidic negative enrichment devices functionalised with anti-CD45.
Publisher: BMJ
Date: 08-2020
DOI: 10.1136/BMJOPEN-2020-039851
Abstract: The COVID-19 pandemic is putting an unprecedented strain on healthcare systems globally. The psychological impact on frontline doctors of dealing with the COVID-19 pandemic is currently unknown. This longitudinal professional survey aims to understand the evolving and cumulative effects of working during the COVID-19 outbreak on the psychological well-being of doctors working in emergency departments (ED), intensive care units (ICU) and anaesthetics during the pandemic. This study is a longitudinal questionnaire-based study with three predefined time points spanning the acceleration, peak and deceleration phases of the COVID-19 pandemic. The primary outcomes are psychological distress and post-trauma stress as measured by the General Health Questionnaire-12 (GHQ-12) and Impact of Events Scale-Revised (IES-R). Data related to personal and professional characteristics will also be collected. Questionnaires will be administered prospectively to all doctors working in ED, ICU and anaesthetics in the UK and Ireland via existing research networks during the s ling period. Data from the questionnaires will be analysed to assess the prevalence and degree of psychological distress and trauma, and the nature of the relationship between personal and professional characteristics and the primary outcomes. Data will be described, analysed and disseminated at each time point however, the primary endpoint will be psychological distress and trauma at the final time point. Ethical approval was obtained from the University of Bath, UK (ref: 4421), and Children’s Health Ireland at Crumlin, Ethics Committee. Regulatory approval from the Health Regulation Authority (UK), Health and Care Research Wales (IRAS: 281944). This study is limited by the fact that it focuses on doctors only and is survey based without further qualitative interviews of participants. It is expected this study will provide clear evidence of the psychological impact of COVID-19 on doctors and will allow present and future planning to mitigate against any psychological impact. ISRCTN10666798 .
Publisher: American Chemical Society (ACS)
Date: 11-02-2016
Abstract: Within an hour, as little as one disseminated tumor cell (DTC) per lymph node can be quantitatively detected using an intraoperative biosensing platform based on silicon nanowire field-effect transistors (SiNW FET). It is also demonstrated that the integrated biosensing platform is able to detect the presence of circulating tumor cells (CTCs) in the blood of colorectal cancer patients. The presence of DTCs in lymph nodes and CTCs in peripheral blood is highly significant as it is strongly associated with poor patient prognosis. The SiNW FET sensing platform out-performed in both sensitivity and rapidity not only the current standard method based on pathological examination of tissue sections but also the emerging clinical gold standard based on molecular assays. The possibility to achieve accurate and highly sensitive analysis of the presence of DTCs in the lymphatics within the surgery time frame has the potential to spare cancer patients from an unnecessary secondary surgery, leading to reduced patient morbidity, improving their psychological wellbeing and reducing time spent in hospital. This study demonstrates the potential of nanoscale field-effect technology in clinical cancer diagnostics.
Publisher: American Chemical Society (ACS)
Date: 03-03-2021
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.TIBTECH.2018.11.001
Abstract: New tools for higher-resolution fetal genome analysis including microarray and next-generation sequencing have revolutionized prenatal screening. This article provides commentary on this rapidly advancing field and a future perspective emphasizing circulating fetal cell (CFC) utility. Despite the tremendous technological challenges associated with their reliable and cost-effective isolation from maternal blood, CFCs have a strong potential to bridge the gap between the diagnostic sensitivity of invasive procedures and the desirable noninvasive nature of cell-free fetal DNA (cffDNA). Considering the rapid advances in both rare cell isolation and low-input DNA analysis, we argue here that CFC-based noninvasive prenatal testing is poised to be implemented clinically in the near future.
Publisher: Cold Spring Harbor Laboratory
Date: 05-2022
DOI: 10.1101/2022.05.01.490183
Abstract: Immuno-specific enrichment of extracellular vesicles (EVs) originating from specific cells/tissues is a promising source of information towards improving insights into cellular pathways underpinning various pathologies and developing novel non-invasive diagnostic methods. Enrichment is an important aspect in mass spectrometry-based analyses of EVs. Herein, we report a protocol for immuno-magnetic enrichment of subtype specific EVs and their subsequent processing for mass spectrometry. Specifically, we conjugated placental alkaline phosphatase (PLAP) antibodies to magnetic iron oxide nanowires (NWs) derived from bacterial biofilms and demonstrated the utility of this approach by enriching placental specific EVs (containing PLAP) from cell culture media. We demonstrate efficient PLAP+ve EV enrichment for both NW-PLAP and Dynabeads™-PLAP, with PLAP protein recovery (83.7±8.9% and 83.2±5.9%, respectively), high particle-to-protein ratio (7.5±0.7×10 9 and 7.1 ± 1.2×10 9, respectively), and low non-specific binding of non-target EVs (7±3.2% and 5.4±2.2%, respectively). Furthermore, our optimized EV enrichment and processing approach identified 2518 and 2545 protein groups with mass spectrometry for NW-PLAP and Dynabead™-PLAP, respectively, with excellent reproducibility (Pearson correlation 0.986 and 0.988). The proposed immuno-specific EVs enrichment and liquid chromatography-tandem mass spectrometry method using naturally occurring iron oxide magnetic NWs or gold-standard Dynabeads™ enables high-quality EV proteomic studies.
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.NEUROSCIENCE.2012.09.034
Abstract: Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disorder caused by a deficiency in the activity of the lysosomal hydrolase, sulphamidase, an enzyme involved in the degradation of heparan sulphate. MPS IIIA patients exhibit progressive mental retardation and behavioural disturbance. While neuropathology is the major clinical problem in MPS IIIA patients, there is little understanding of how lysosomal storage generates this phenotype. As reduced neuronal communication can underlie cognitive deficiencies, we investigated whether the secretion of neurotransmitters is altered in MPS IIIA mice utilising adrenal chromaffin cells, a classical model for studying secretion via exocytosis. MPS IIIA chromaffin cells displayed heparan sulphate storage and electron microscopy revealed large electron-lucent storage compartments. There were also increased numbers of large/elongated chromaffin granules, with a morphology that was similar to immature secretory granules. Carbon fibre erometry illustrated a significant decrease in the number of exocytotic events for MPS IIIA, when compared to control chromaffin cells. However, there were no changes in the kinetics of release, the amount of catecholamine released per exocytotic event, or the amount of Ca(2+) entry upon stimulation. The increased number of large/elongated granules and reduced number of exocytotic events suggests that either the biogenesis and/or the cell surface docking and fusion potential of these vesicles is impaired in MPS IIIA. If this also occurs in central nervous system neurons, the reduction in neurotransmitter release could help to explain the development of neuropathology in MPS IIIA.
Publisher: American Chemical Society (ACS)
Date: 18-11-2014
DOI: 10.1021/AM505201S
Abstract: Rapid, reliable and unbiased circulating tumor cell (CTC) isolation and molecular characterization methods are urgently required for implementation in routine clinical diagnostic and prognostic procedures. We report on the development of a novel unbiased CTC detection approach that combines high-throughput automated microscopy with a simple yet efficient approach for achieving a high level of tumor cell binding in standard tissue culture polystyrene (PS) well plates. A single 5 min high-power oxygen plasma treatment was used to create homogeneous nanoscale roughness on standard PS tissue culture plates and, in turn, drastically enhance the binding of a range of tumor cells. After physical adsorption of an adlayer of poly-l-lysine, binding yields above 97% were obtained at 2 h for all tumor cell lines used in the study. Morphological analysis of the cells confirmed strong adherence to the nanorough PS substrates. Clinically relevant concentrations of a highly metastatic breast cancer cell line, used as model for CTCs, could be reliably detected among blood cells on the nanorough polystyrene plates using an automated microscopy system. The approach was then successfully used to detect CTCs in the blood of a stage IIIc colorectal cancer patient. By combining the high binding abilities of nanorough PS well plates with the high-throughput nature of high-content analysis systems, this methodology has great potential toward enabling unbiased routine clinical analysis of CTCs. It could be applied, once clinically validated, in any clinical center equipped with an automated microscopy facility at a fraction of the cost of current CTC isolation technologies.
Publisher: Springer Science and Business Media LLC
Date: 2015
No related grants have been discovered for Marnie Winter.