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    19683 research outputs found

    Exploring Zoom Interactions Towards Understanding Communicative Practices in Video Mediated Interactions

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    A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Education, La Trobe University, Victoria, Australia.</p

    Canary Wharf: The Rock Opera

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    A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Humanities and Social Sciences, La Trobe University, Victoria, Australia.</p

    Oncogenic small extracellular vesicles enriched in sphingosine-1-phosphate play a crucial role in pancreatic cancer progression

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    Small extracellular vesicles (sEVs) from tumour cells mediate intercellular communication and signalling to regulate the progression of pancreatic ductal adenocarcinoma (PDAC). While we and others have shown that PDAC-derived sEVs comprise oncogenic protein and nucleic acid cargo, understanding the lipid landscape of these sEVs remains unknown. Lipids influence both the composition of sEVs and their roles in lipid metabolism and signalling pathways within the tumour microenvironment and tumorigenesis. We hypothesised that specific lipids in oncogenic sEVs might provide insights into PDAC. Comprehensive mass spectrometry-based lipidomic analysis was performed using liquid chromatography-electrospray ionisation-tandem mass spectrometry on sEVs isolated from PDAC and non-malignant pancreatic cell lines, patient-derived xenograft cell lines and plasma from the PDAC transgenic mouse model KPC (KRASWT/G12D/ TP53WT/R172H/Pdx1-Cre+/+). The sEV lipidomic analyses identified over 700 lipid species from 25 lipid classes and subclasses. Our results showed that, compared to non-malignant cells, PDAC-derived sEVs were enriched in specific lysophospholipids, particularly sphingosine-1-phosphate (S1P), a lipid known for its pivotal role in cancer pathogenesis. S1P enrichment was validated in plasma-derived sEVs from KPC mice compared to WT. To explore the functional implications of S1P enrichment, we conducted assays demonstrating that S1P in sEVs facilitated tubule formation in human microvascular endothelial cells and promoted cancer-associated fibroblast cell migration. We show that PDAC-derived sEVs are differentially enriched in specific lipids associated with cancer phenotype. Our findings highlight that PDAC-derived sEVs are enriched in specific lipids, particularly S1P, which plays a crucial role in promoting cancer progression.</p

    Challenges and Opportunities in Quantifying Bioactive Compounds in Human Breastmilk

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    Breastmilk is a complex biological fluid containing over a thousand bioactive proteins, lipids, cells and small molecules that provide nutrition and immunological protection for infants and children. The composition of breastmilk is unique to each individual and can also vary within individuals according to breastfeeding duration, maternal health, time of day, and other factors. As such, the composition of breastmilk can be considered a “fingerprint” that could be interrogated to identify biomarkers of breast health and disease. However, accurate quantification of bioactive components in breastmilk remains a significant challenge. Approaches such as immunoassays and mass spectrometry have been largely applied to study blood or other biological fluids and require validation and optimisation before these techniques can be used to accurately quantify bioactive compounds in breastmilk. Development of protocols specific to breastmilk should be carried out with high precision, confidence, and sensitivity. This review explores the challenges and opportunities associated with different techniques for quantification of breastmilk bioactive components.</p

    Exploring Play-Based Learning in the Eastern Region of Saudi Arabia

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    Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Education, La Trobe University, Victoria, Australia.</p

    The political economy of accountability ecosystems: Charting a new course in the Pacific

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    “Accountable and responsive governance is essential for states to deliver on the needs and interests of their publics. But despite investments in strengthening accountability over many decades, these approaches have often failed to gain traction and accountability continues to fall short of meeting people’s needs and expectations. This is true in the Pacific – the focus of this paper – where development partner approaches to accountability have largely focused on importing external standards and forms that often produce only thin results. Wider questioning within the development community of good governance and the open movement underline the need for new approaches.”</p

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