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Bone marrow-derived mesenchymal stem cells mitigate chronic colitis and enteric neuropathy via anti-inflammatory and anti-oxidative mechanisms
No full textCurrent treatments for inflammatory bowel disease (IBD) are often inadequate due to limited efficacy and toxicity, leading to surgical resection in refractory cases. IBD’s broad and complex pathogenesis involving the immune system, enteric nervous system, microbiome, and oxidative stress requires more effective therapeutic strategies. In this study, we investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell (BM-MSC) treatments in spontaneous chronic colitis using the Winnie mouse model which closely replicates the presentation and inflammatory profile of ulcerative colitis. The 14-day BM-MSC treatment regimen reduced the severity of colitis, leading to the attenuation of diarrheal symptoms and recovery in body mass. Morphological and histological abnormalities in the colon were also alleviated. Transcriptomic analysis demonstrated that BM-MSC treatment led to alterations in gene expression profiles primarily downregulating genes related to inflammation, including pro-inflammatory cytokines, chemokines and other biomarkers of inflammation. Further evaluation of immune cell populations using immunohistochemistry revealed a reduction in leukocyte infiltration upon BM-MSC treatment. Notably, enteric neuronal gene signatures were the most impacted by BM-MSC treatment, which correlated with the restoration of neuronal density in the myenteric ganglia. Moreover, BM-MSCs exhibited neuroprotective effects against oxidative stress-induced neuronal loss through antioxidant mechanisms, including the reduction of mitochondrial-derived superoxide and attenuation of oxidative stress-induced HMGB1 translocation, potentially relying on MSC-derived SOD1. These findings suggest that BM-MSCs hold promise as a therapeutic intervention to mitigate chronic colitis by exerting anti-inflammatory effects and protecting the enteric nervous system from oxidative stress-induced damage.</p
Computational Evidence for Bisartan Arginine Blockers as Next-Generation Pan-Antiviral Therapeutics Targeting SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses
No full textSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains. This study introduces a new generation of potent sartans, known as bisartans, engineered in our laboratories with negative charges from carboxylate or tetrazolate groups. These anionic tetrazoles interact strongly with cationic arginine residues or metal cations (e.g., Zn2+) within viral and host target sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, and the RSV fusion protein. Using virtual ligand docking and molecular dynamics, we investigated how bisartans and their analogs bind to these viral receptors, potentially blocking infection through a pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable and high-affinity docking to key catalytic domains of the SARS-CoV-2 NSP3, H1N1 neuraminidase, and RSV fusion protein, outperforming FDA-approved drugs like Paxlovid and oseltamivir. It also showed strong binding to the arginine-rich furin cleavage sites S1/S2 and S2', suggesting interference with SARS-CoV-2's spike protein cleavage. The results highlight the potential of tetrazole-based bisartans as promising candidates for developing broad-spectrum antiviral therapies.</p
Inflammation: The Cause of All Diseases
No full textInflammation is an essential biological process that serves as the body’s first line of defence against harmful stimuli, including pathogens, damaged cells, and irritants. While acute inflammation is crucial for healing and recovery, chronic inflammation can lead to a variety of diseases, including cancer, cardiovascular disorders, and autoimmune conditions. The recent Special Issue, ‘Inflammation: The cause of all diseases 2.0’ along with the participating journals—Cells, Diseases, Healthcare, International Journal of Molecular Sciences, and Vaccines—sheds light on the complex interplay between inflammation and disease mechanisms, providing valuable insights into potential therapeutic strategies targeting inflammatory pathways.</p
The Indo-Pacific’s Broadcast Landscape, Strategic and Military Value
No full textThis chapter establishes the context for understanding the importance of transnational broadcasting for nation states, defines what we mean by the Indo-Pacific region, and briefly discusses the defence and other geopolitical conditions that influence the funding of broadcasters within an increasingly global media ecosystem. It notes that broadcast technology and digital platforms are changing the way the media operates in the region acknowledging that more than two billion people now using a Meta product (Facebook, Instagram, WhatsApp). By drawing on literature across media, international relations and defence, this chapter considers the value of transnational broadcasters and their influence in the media sector before establishing the overall argument that, despite changes in technology, international broadcasting has value well beyond geo-strategic factors
Skyring
No full textResearch Background Skyring investigates the intersection of Scandinavian matrilineage, contemporary installation practice, and ritual performance. This project builds upon established research into the symbolic significance of circular forms in Norse and Scandinavian culture—as emblems of community, continuity, and cyclical knowledge transmission. The work engages with historical precedents in women's esoteric art practice, particularly the alchemical and symbolic languages developed by artists such as Hilma af Klint and Anna Cassel, who employed geometric abstraction and personal symbolism to challenge patriarchal artistic hierarchies. The project comprises paintings with crystalline surfaces, suspended luminescent objects, polished metal sculptures including a hovering mobius ring, and the performance work Trollkjerring (Troll Queen), which reinterprets Henrik Ibsen's Peer Gynt through a female-centric lens. Research Significance This work advances understanding of how contemporary artists mobilize ancestral knowledge systems and matrilineal inheritance within installation and performance contexts. By centering the female perspective in traditionally male-dominated narratives (transforming the Mountain King's hall into the Mountain Queen's domain), the project contributes to feminist reclamations of cultural mythology. The research demonstrates how ritual performance can function as a method of intergenerational knowledge transfer, with family members enacting roles that embed personal biography within larger cultural frameworks. The deployment of reflective, refractive materials creates an environment where meaning multiplies and fragments—echoing Lacanian theories of mirror-stage identity formation while establishing a theatrical space charged with what the work terms "arcane energies" and "remanent dynamism." Research Contribution Skyring contributes methodologically by modeling how artists can synthesize installation, object-making, and participatory performance to create immersive cosmologies. The work expands vocabularies for discussing material mystification in contemporary art, particularly through its lexicon of "talisman shapes" and enchanted objects. By documenting the transmission of esoteric artistic practices from one generation to the next (symbolized through the daughter emerging into the white circle), the project offers new frameworks for understanding artistic lineage beyond institutional canonization. The research validates alternative knowledge systems—pagan, matriarchal, ritualistic—as legitimate sources for contemporary artistic inquiry, while demonstrating how personal ancestry can ground experimental practice in specific cultural traditions without resorting to nostalgia or appropriation.</p
Shelter of Hollows
No full textResearch Background Shelter of Hollows is a large-scale suspended sculpture for Macquarie's North Tower that investigates the poetics of void and hollow form through site-specific public art practice. The work connects across Martin Place station to another work Continuum by translating and transitioning geometric impossibilities—the Möbius strip and Klein bottle—into organic cavernous forms. This research engages critically with Australian modernist sculptors Margel Hinder, Tom Bass, and Lyndon Dadswell (whose works from 1964 anchor the Martin Place precinct), examining their investigations of positive/negative space, organic abstraction, and architectural relief. The cave motif functions as both material investigation and theoretical framework, drawing on architectural theory, Platonic philosophy, and feminist spatial theory to explore hollow forms as sites of generative absence. Research Significance This work advances knowledge in sculptural form by recontextualising mid-century Australian modernist concerns with void and organic abstraction for contemporary public art contexts. It contributes new methodologies for site-responsive practice that engage infrastructural transit spaces—train stations, commuter hubs—as sites for conceptual exploration rather than mere decoration. The suspended sculpture creates formal and conceptual dialogues across time, establishing intergenerational conversations about sculptural form between Dadswell, Hinder, Bass, and contemporary practice. By inverting the cave—turning it inside out—the work challenges conventional relationships between interior/exterior, presence/absence, operating as both object and inhabited space within the cavernous North Tower architecture. Research Contribution Shelter of Hollows contributes original knowledge through its material synthesis of earthen elements—ceramics, metal, glass—that reference industrial transit infrastructure while creating unexpected sculptural alchemy. The work demonstrates how geometric abstraction can morph into organic form while maintaining conceptual rigor, offering new approaches to representing temporal passage and human continuity through static sculpture. It establishes a practical model for public art that operates simultaneously as architectural intervention, historical homage, and theoretical proposition. The research validates hollow form as generative conceptual territory, proving sculptural absence can be dynamically present. This advances public art practice by showing how suspended work in commuter spaces can embody multiple temporalities—ancient (cave), historical (1960s modernism), contemporary (transit infrastructure)—creating layered meaning accessible to diverse publics.</p
Techno-economic Evaluation of Integrated Green Hydrogen System
No full textThis PhD thesis presents a comprehensive techno-economic evaluation of the green hydrogen supply chain, focusing on producing green hydrogen using desalinated water and its export as ammonia. The research aims to bridge significant knowledge gaps in the field by analysing the technical and economic viability of the proposed hydrogen production and supply pathway. The key objectives include performing techno-economic analysis of each process in the green hydrogen-ammonia supply chain, assessing the cost-effectiveness of using desalinated water for hydrogen production through PEM electrolysis, evaluating the integration of green hydrogen into ammonia production and its economic implications, comparing ammonia cracking technologies using CSIRO's metal membrane and conventional PSA methods, and exploring the potential of vertical integration in enhancing the economic feasibility of the green hydrogen supply chain.The methodologies employed in this research include comprehensive mass balance and equipment sizing calculations for each process in the supply chain, such as desalination, PEM electrolysis, ammonia synthesis, and ammonia cracking. These calculations were based on standard engineering practices and relevant literature. Various economic models were utilised, including capital and operating cost models, cash flow analysis, and profitability analysis, to estimate initial investments, ongoing costs, and financial returns. Detailed techno-economic assessments were conducted for each process, focusing on efficiency, cost-effectiveness, and scalability, and included sensitivity studies to evaluate the impact of key variables on the overall feasibility of the supply chain.The findings of the research indicate that the integration of desalination plants with PEM electrolysis is a viable pathway for green hydrogen production, with the cost of desalinated water, hydrogen and ammonia significantly impacting the overall cost of hydrogen production. PEM electrolysis was confirmed as an efficient method for green hydrogen production, with advancements in materials and manufacturing processes contributing to reduced costs and improved durability. The integration of green hydrogen into ammonia synthesis processes demonstrated substantial environmental and economic benefits, with renewable energy sources for hydrogen production significantly reducing the carbon footprint of ammonia production. The comparison of ammonia cracking technologies highlighted the advantages of CSIRO's metal membrane technology in terms of efficiency and cost-effectiveness, though further investigation is required for scaling up this technology. Additionally, the potential benefits of vertical integration in the green hydrogen supply chain were explored, suggesting that vertical integration could enhance efficiency, reduce costs, and improve the overall economic viability of green hydrogen projects.In conclusion, this thesis provides a detailed and robust techno-economic evaluation of a green hydrogen supply chain, offering valuable insights for scientists, engineers, and policymakers. The findings highlight the potential of using desalinated water for hydrogen production and the economic benefits of integrating green hydrogen into ammonia synthesis and cracking processes. The research underscores the importance of strategic investments and technological innovations in advancing the green hydrogen economy. The insights gained from this study contribute to the growing body of knowledge on sustainable energy systems and provide a solid foundation for future research and development in green hydrogen supply chains.</p
Modification of plant and algal proteins through conjugation and complex coacervation for application as emulsifiers and encapsulants
No full textProteins are widely used as emulsifiers and encapsulants in food industry. In recent years, there has been a growing demand for non-animal proteins (particularly plant and algal ones) as alternative protein ingredients to be used as emulsifiers and encapsulants. This trend is driven by increasing consumer preference for sustainably sourced food ingredients and also due to increasing vegetarian and vegan lifestyle. However, the application of plant and algal proteins as emulsifiers and encapsulants is limited due to their relatively inferior solubility, emulsifying activity and interfacial properties. Covalent conjugation and/or non-covalent complexation (e.g., electrostatic charge driven complex coacervation) of protein with polysaccharide can be used to improve their techno-functional properties. For example, covalent bonding between the ɛ-amino group of lysine residues of proteins and the terminal reducing group of the carbonyl of polysaccharides produces conjugates, and these conjugates show improved solubility and emulsifying properties compared to unconjugated proteins. Complex coacervation occurs when positively charged proteins are brought in contact with negatively charged polysaccharides. Complex coacervates are also known to show better emulsifying properties compared to the uncomplexed proteins. Protein-polysaccharide conjugates and complex coacervates bring together the surface-active nature of proteins and steric hindrance and greater water solubility of polysaccharides and make them more effective as emulsifiers and encapsulants of unstable (yet valuable) compounds.
There is a vast pool of knowledge on Maillard reaction driven covalent conjugation and complex coacervation of milk proteins and animal proteins (e.g., gelatin) with polysaccharides. There is a paucity of research on Maillard reaction driven conjugation of plant and algal proteins, especially when implemented through ‘wet-heating’ route. Wet-heating route involves carrying out Maillard reaction in aqueous medium under suitably chosen temperature and time and is known to be shorter and easy to control compared to conventional dry-heating route. There is no systematic research on complex coacervation of (already) conjugated proteins with polysaccharides. Furthermore, the efficacy of resulting complex coacervates of conjugated proteins as emulsifiers and encapsulants remains unknown. Therefore, this thesis aimed to gain greater insights into the Maillard reaction-induced conjugation of plant and algal proteins followed by complex coacervation. The practical significance of this work was to improve the emulsifying and encapsulating properties of plant and algal proteins by creating conjugates and their complex coacervates. Pea protein isolate (PPI) and Spirulina protein concentrate (SPC) were chosen as model plant and algal proteins. Maltodextrin (MD) and carrageenan (CG) were chosen as model polysaccharides for producing conjugates and complex coacervates, respectively. The Maillard-reaction induced conjugation of PPI and SPC with maltodextrin was optimised in terms of temperature and time so that the reaction remained confined to initial stage. The complex coacervation between SPC-MD conjugate with CG was optimised in terms of pH and protein-to-polysaccharide ratio. Both conjugates and complex coacervates were used as emulsifiers and encapsulants of oxygen-sensitive omega 3 rich oil and their effectiveness in encapsulating and delivering encapsulated oil to intestinal stage of digestion were investigated.
The first experimental chapter was dedicated to implement and optimise the wet-heating route of Maillard reaction between PPI and maltodextrin (MD). The conjugation between PPI and MD, as well as the progression of Maillard reaction, were assessed by detecting the colour change and the formation of brown-pigmented melanoidins. The optimum reaction conditions in terms of pH, temperature and time were found to 8.0, 90 oC and 5 h, respectively. The Maillard reaction induced conjugation between PPI and MD was successfully controlled within the initial stage since there was no significant formation of melanoidins up to 5 h of reaction. The solubility, surface charge and emulsifying properties of the PPI were significantly improved after conjugating with MD.
The second experimental chapter focused on the conjugation between Spirulina protein concentrate (SPC) and MD, based on the information obtained from the conjugation of PPI and MD. The glycation degree, molecular weight, secondary structure, solubility, surface hydrophobicity, antioxidant activity and emulsifying properties of the resulting SPC-MD conjugates were determined. The stability of oil-in-water (O/W) emulsions produced using SPC-MD conjugates as the emulsifier under thermal treatment was also evaluated. The conjugation of SPC with MD increased the solubility of SPC when the reaction was carried out for 6 h, beyond which the solubility decreased. The resulting SPC-MD conjugates significantly increased emulsifying properties as well as antioxidant activity. O/W emulsions stabilised by SPC-MD conjugates also showed higher thermal stability.
The third experimental chapter investigated the complex coacervation between conjugated SPC (i.e., SPC-MD conjugates) and CG. The optimum conditions for the formation of complex coacervates were found to be (SPC-MD conjugate)-to-CG ratio of 24:1 (w/w) and pH of 3.0. The resulting (SPC-MD conjugate)-CG complex coacervates were then used as encapsulation wall materials to encapsulate canola oil at a core-to-wall ratio of 1:3 (w/w). The particle size, encapsulation efficiency, thermal stability, and oxidative stability of the resulting microcapsules were determined. The microcapsules produced using conjugate-based coacervates as encapsulants showed significantly higher encapsulation efficiency (92.5%) and lower surface oil content (1.52%) compared to those produced using complex coacervates of unconjugated SPC. The microcapsules produced using (SPC-MD conjugate)-CG coacervates also had much higher thermal and oxidative stability.
The fourth experimental chapter focused on gaining insight into the in-vitro digestion behaviour of solid microcapsules stabilised by (SPC-MD conjugate)-CG coacervates. An in-vitro adult model that included oral, gastric, and intestinal stages was used for this purpose. The particle size, microstructure, free amino acid contents, molecular weight, released oil content and free fatty acid content at the end of each stage were determined. The conjugate-based coacervates, as encapsulating shell materials, were effective in protecting encapsulated oil against gastric digestion. Most of the encapsulated oil (62-67%) was released during the intestinal stage, primarily due to slow proteolysis of wall material. Lipolysis of released oil in the intestinal stage released up to 41.7% free fatty acids. Thus, (SPC-MD conjugate)-CG coacervates showed significant potential as wall materials to encapsulate oxygen-sensitive oils for their targeted delivery and controlled release in the intestinal stage of digestion.
The findings from this thesis make a valuable contribution to the body of knowledge on the scientific aspects of Maillard reaction and complex coacervation, particularly in the complex coacervation of (already) conjugated protein. The findings also establish that wet-heating route of Maillard reaction of plant and algal protein can be controlled within initial stage, and the formation of advanced glycation end products (AGEs) can be avoided. The conjugates and their complex coacervates of plant and algal proteins can be used as healthy and sustainable emulsifiers and encapsulants of oxygen-sensitive compounds, such as omega-3 rich oils, in the food industry
Understanding the mechanism of formation and inhibition of protein fibrils for treatment and prevention of neurodegenerative disease
No full textNeurodegenerative disorders such as Alzheimer’s disease (AD) are characterised by permanent & progressive impairment to cognitive function. Amyloid-beta (Aβ) peptide which is formed by cleavage of the amyloid precursor protein (APP), undergoes significant morphological changes that result in aggregation and the formation of β-sheet fibril plaque deposits. Deposition of amyloid plaque onto brain tissue leads to gradual loss of function which is observed symptomatically as memory loss, speech impairment and confusion.
Inhibition of Aβ fibril formation as well as the prevention and destabilisation of pre-formed fibrils hold significant interest as therapeutic approaches to AD treatment. Drugs currently approved for AD treatment have poor bioavailability and cause significant side effects, while only supressing symptoms of AD.
Natural products including EGCG (Epigallocatechingallate), curcumin, resveratrol, rottlerin and ascorbic acid have shown promising anti-amyloidogenic affects which appear to disturb the fibrillation mechanism of Aβ in vitro. Additionally, these compounds have also indicated potential to disrupt the highly ordered structure of β-sheet fibrils, leading to neuronal cell protection. Unfortunately, poor bioavailability caused by metabolization in the gut or low degrees of blood brain barrier (BBB) permeability hinders the therapeutic applications of these compounds.
Spirooxindoles have been reported to be versatile structures which are naturally occurring and exhibit many protective abilities. Some reports discuss their anti-bacterial and anti-cancer applications however limited literature is available surrounding their anti-amyloidogenic properties.
To characterise the mechanistic involvement of spirooxindole compounds against fibril formation and fibril destabilisation, screening against fibril formation was performed using a series of experimental techniques including Thioflavin T (ThT) fluorescence assay’s, Raman Spectroscopy, Transmission electron microscopy (TEM) and finally Circular Dichroism (CD).
Hen egg white lysozyme (HEWL) was used as a model protein, since it undergoes fibrillation under mild denaturing conditions involving a pH 2.0 environment while being incubated at 60 °C. Based on the ThT data collected on the library of synthesised spirooxindole compounds, three displayed promising anti-amyloidogenic activity which led to further biophysical studies. Raman spectroscopy was incorporated to monitor the morphological transitions of HEWL’s secondary structure during fibrillogensis. Considerable differences in fibrillation were observed with and without the inhibitor compounds and upon interpretation of these changes, we suggest that the addition of the spirooxindole compounds redirect the mechanism of HEWL fibrillation to the formation of an alternative structure which we describe as a highly disordered oligomeric aggregate. These observations were confirmed by the CD data which confirmed the results presented by the Raman measurements. TEM images suggested that the presence of increased concentrations of the spirooxindole compounds resulted in a lower degree of fibrillar structural formation.
ThT fluorescence and Raman Spectroscopy also confirmed the ability for the spirooxindole compounds to break down the highly ordered structure of HEWL fibrils. The addition of the compounds to solutions of pre-formed HEWL fibrils resulted in the formation of disordered structure which we described as an alternate aggregate state. Once again, this was confirmed by the CD interpretation as well as the visual representation given by the TEM images. TEM indicated that when fibrils were exposed to the inhibitor compounds, the resultant structures were clumpy aggregates instead of thick fibrillar strands. The formation of these aggregated disordered structures indicates that the addition of the spirooxindole compounds to pre-formed fibrils results in substantial disruption of the hydrogen bonding along with the amino acid side chain hydrophobic interactions which give fibrils their highly ordered structure.
Permeating the BBB is an extremely important property for an anti-amyloidogenic drug to have. As discussed earlier, a drawback for many compounds which have been discussed in the literature was poor BBB permeability. Although the spirooxindole compounds have significantly hydrophobic structures, ensuring a high degree of BBB permeation is extremely important. Introducing drug carriers such as cubosomes which are made up of a monoolein (MO), a single-chain amphiphile which forms lipid phases in aqueous solutions were found to be highly effective. By encapsulating the spirooxindole compounds within the MO cubosomes, we discovered that the structural integrity of the cubosome, shown by little to no changes in relative size and charge highlighted by dynamic light scattering (DLS) and lattice parameter highlighted by small angle X-ray scattering (SAXS). SAXS also indicated that upon encapsulating the compounds within the cubosomes the overall cubic phase remained largely unaffected. UV-Vis spectroscopy was used to determine the encapsulation efficiency of each spirooxindole compound. By measuring the concentration of free-floating compound in the cubosomes solution, we determined that the encapsulation efficiency of the compounds was >98%. A parallel artificial membrane permeability assay (PAMPA) was performed to quantify the relative permeability of the compounds before and after encapsulating within cubosomes. We found that upon encapsulation, significant increases in relative permeability can be observed, which indicate that cubosomes can be used to effectively carry the spirooxindole compounds across the BBB where their anti-amyloidogenic properties can be demonstrated
Exploring options for reforming Australian corporate law based on the UN Guiding Principles Framework
No full textBusinesses worldwide continue to face the pervasive issue of human rights violations within global supply chains. Despite universal agreements to eradicate such violations, many corporations remain passive, resulting in the ineffectiveness of voluntary human rights due diligence. This study aims to reconcile Australian corporate law with the United Nations Guiding Principles on Business and Human Rights (UNGPs). Guided by the UNGPs and informed by a multi-theoretical framework, this research has two main objectives. The first is to explore how Australian corporate law can be restructured to reflect the UNGPs by considering laws from diverse jurisdictions. The second is to assess the feasibility of reforming Australian corporate law, considering the sociopolitical and economic distinctions between Australia and the legal sources of inspiration.
A comparative analysis of legal instruments from Australia, the UK, the USA, France, and Germany was conducted to achieve these objectives. The study identifies that Australian corporate law inadequately supports human rights, only giving them regard when there is a foreseeable corporate advantage or the lack of detriment. The research suggests three pivotal areas for reform: enhancing human rights in board decisions, integrating human rights due diligence by stakeholder representation, and introducing access to remedies for victims of human rights violation by businesses.
Given the complexities surrounding the reformation of Australian corporate law, the study proposes the adoption of an alternative corporate structure: the benefit corporation option. This structure, inspired by the B Lab Australia New Zealand (B Lab ANZ) legal framework, allows businesses to pursue both profit and social objectives. Drawing from institutional theories, the B Lab ANZ framework is posited as an "institutional bypass" to existing barriers. The research further recommends access to remedy provision, especially for large corporations, inspired by French and German laws, ensuring alignment with the UNGPs.
In conclusion, the study highlights the pressing need for Australian corporate law to evolve and proposes potential reforms to achieving greater alignment with global human rights standards