Dendritic Cell Targeted Therapy Utilising Porous Silicon Nanoparticles for the Induction of Immunological Tolerance

The work depicted in this thesis, explores the use of drug loaded porous silicon nanoparticles (pSiNP) targeted to dendritic cells both in vitro and in vivo. Paper one explores the in vitro application of rapamycin loaded, DC-SIGN pSiNP to induces a maturation resistant, tolerogenic state within human monocyte derived DC. Furthermore, it explores the poor stimulatory ability of these tolerogenic DC within an allogeneic immune system. The study concluded that nanoparticles functionalised with DC-SIGN antibody, were capable of tracking to human monocyte derived DC expeditiously compared to their isotype counterparts. DC-SIGN pSiNP were also able to release their payload and induce a tolerogenic state in DC in vitro. Paper two develops the work from paper one exploring the in vivo tracking capability of the nanoparticle within both murine and non-human primate animal models. Within mice, the functionalisation of the pSiNP with antibodies permitting targeting to DC (CD11c receptor) significantly enhanced their tracking abilities to splenic DC populations, compared to isotype pSiNP. Within both murine and nonhuman primate animal models, a serendipitous discovery was the enhanced kidney tracking abilities of the DC targeting pSiNP. This opens the door for the development of potentially new drug delivery methods more localised to the kidneys. Following in vivo tracking experiments, paper two explored the ability of drug and peptide loaded nanoparticle to enhance regulatory T-cell populations in vivo by targeting DC. It was concluded that the CD11c pSiNP were capable of significantly increasing the number of splenic regulatory T-cells when compared to the control animals, which did not receive pSiNP. These two papers identify a novel strategy for promoting drug delivery to a scarce cell population and the ability to promote regulatory T-cell generation in vivo without ex vivo modification of DC, which is more commonly seen today. The results show promise for future development of an enhanced drug delivery method to modify the immune system.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201

Availability and usefulness of economic data on the effects of aquaculture: a North Atlantic comparative assessment

This paper focuses on the availability of economic indicators and metrics to assess effects of marine aquaculture production in the North Atlantic area (the EU, Norway, Canada and USA), including also social and environmental effects. We consider how aquaculture planning and management is organised in the different countries and the usefulness of economic information to address different aquaculture‐related policies. We find that the most relevant economic data for aquaculture management should be at the local and regional levels rather than nationally. The availability of such economic data is mapped for national, regional and local level. The focus is on data that are publicly available from authorities or research institutions. The availability of data is generally fairly good for national and regional data on the direct economic effects of aquaculture. Data on how aquaculture‐related products or input markets are affected are however poorly available, as are economic data on external effects from aquaculture. Countries with a larger aquaculture sector tend to have better availability of aquaculture‐related economic data than those with a smaller sector. An index is developed and calculated to show more specifically where the countries have relatively good or poor data availability compared to their needs. While it will not always be cost‐effective or meaningful to collect economic data on the effects of aquaculture, our study indicates that several countries could benefit from expanding such data collection. It can make trade‐off decisions more consistent and easier to perform, and aquaculture policies and measures can be better tailored to specific contexts

Co-culture of sea cucumber Holothuria scabra and red seaweed Kappaphycus striatum

Commercially valuable sea cucumbers are potential co‐culture species in tropical lagoon environments, where they may be integrated into established aquaculture areas used for seaweed farming. In the current study, wild‐caught juvenile sea cucumbers, Holothuria scabra, and red seaweed Kappaphycus striatum were co‐cultured on Zanzibar, United Republic of Tanzania. Sea cucumbers (97 g ± 31 SD, n = 52) were cultured in mesh enclosures at initial cage stocking densities of 124 ± 21 SD and 218 ± 16 SD g m−2 under seaweed culture lines. Over 83 days, individual growth rate (1.6 g d−1 ± 0.2 SD) of sea cucumbers at low stocking density was significantly higher (χ2 = 8.292, d.f. = 1, P = 0.004) than at high‐stocking density (0.9 g d−1 ± 0.1 SD). Seaweed individual growth rates [6.27 (±0.3 SE) g d−1] were highest in co‐culture with sea cucumber at low density but did not differ significantly from high sea cucumber density or seaweed monoculture treatments (χ2 = 3.0885, d.f. = 2, P = 0.2135). Seaweed growth varied significantly (χ2 = 35.6, d.f. = 2, P < 0.0001) with sampling period, with the final sampling period resulting in the highest growth rate. Growth performance for seaweed and sea cucumbers (χ2 = 3.089, d.f. = 2, P = 0.21 and χ2 = 0.08, d.f. = 1, P = 0.777 respectively), did not differ significantly between monoculture and co‐culture treatments, yet growth in co‐culture was comparable with that reported for existing commercial monoculture. Results indicate H. scabra is a highly viable candidate species for lagoon co‐culture with seaweed. Co‐culture offers a more efficient use of limited coastal space over monoculture and is recommended as a potential coastal livelihood option for lagoon farmers in tropical regions

A revolution without people? Closing the people-policy gap in aquaculture development

Failure of the blue revolution is a global risk. The international problem is that there is a gap in knowledge exchange between the aquaculture industry, policy makers trying to support aquaculture development and people who depend on aquaculture for a job and/or food source. Thus, governments and international organizations promoting aquaculture as the solution to improving food security, nutrition and income are failing to optimise production of natural aquatic resources. We identify a "people-policy gap", and suggest that this is an understudied constraint, which needs to be overcome before worldwide food security can be achieved from aquatic environments. We argue that this gap leads to uneven distribution of benefits, a disconnection between benefits and local needs, and detrimental effects on human health and food security, all of which can have negative repercussions on human communities and ecosystems. In order to address this need, we present an analytical framework to guide context specific, policy-relevant assessments of the social, economic and ecological dimensions of aquaculture on a case-by-case basis. The framework is designed to make best use of existing data and scientific tools for decision-making. In conclusion, we argue for: equal consideration of ecological, social and economic issues in aquaculture policy-making; pre-emptive identification of likely social impacts; integration of people- and context-specific social framing conditions into planning and policy review; addressing the social disconnection between global consumption and production; and, encouragement of creative combinations of theories and methods to assess and interpret the social dimensions of aquaculture in multiple contexts

Encapsulation of Human Natural and Induced Regulatory T-Cells in IL-2 and CCL1 Supplemented Alginate-GelMA Hydrogel for 3D Bioprinting

2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Regulatory T-cells (Tregs) are important modulators of the immune system through their intrinsic suppressive functions. Systemic adoptive transfer of ex vivo expanded Tregs has been extensively investigated for allogeneic transplantation. Due to the time-consuming and costly expansion protocols of Tregs, more targeted approaches could be beneficial. The encapsulation of human natural and induced Tregs for localized immunosuppression is described for the first time. Tregs encapsulated in alginate-gelatin methacryloyl hydrogel remain viable, phenotypically stable, functional, and confined in the structure. Supplementation of the hydrogel with the Treg-specific bioactive factors interleukin-2 and chemokine ligand 1 improves Treg viability, suppressive phenotype, and function, and attracts to the structure CCR8+ T-cells enriched with anti-inflammatory subpopulations, including Tregs, from human peripheral blood. Furthermore, these findings are applicable to 3D bioprinting. Co-axial printing of murine pancreatic islets with human natural and induced Tregs protects the islets from xenoresponse upon co-culture with human peripheral blood mononuclear cells. This establishes the co-encapsulation of Tregs by co-axial 3D bioprinting as a valid option for providing local immune protection to allogeneic cellular transplants such as pancreatic islets

Encapsulation of Human Natural and Induced Regulatory T-Cells in IL-2 and CCL1 Supplemented Alginate-GelMA Hydrogel for 3D Bioprinting

2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Regulatory T-cells (Tregs) are important modulators of the immune system through their intrinsic suppressive functions. Systemic adoptive transfer of ex vivo expanded Tregs has been extensively investigated for allogeneic transplantation. Due to the time-consuming and costly expansion protocols of Tregs, more targeted approaches could be beneficial. The encapsulation of human natural and induced Tregs for localized immunosuppression is described for the first time. Tregs encapsulated in alginate-gelatin methacryloyl hydrogel remain viable, phenotypically stable, functional, and confined in the structure. Supplementation of the hydrogel with the Treg-specific bioactive factors interleukin-2 and chemokine ligand 1 improves Treg viability, suppressive phenotype, and function, and attracts to the structure CCR8+ T-cells enriched with anti-inflammatory subpopulations, including Tregs, from human peripheral blood. Furthermore, these findings are applicable to 3D bioprinting. Co-axial printing of murine pancreatic islets with human natural and induced Tregs protects the islets from xenoresponse upon co-culture with human peripheral blood mononuclear cells. This establishes the co-encapsulation of Tregs by co-axial 3D bioprinting as a valid option for providing local immune protection to allogeneic cellular transplants such as pancreatic islets

Don't tell me what I should do, but what others do: The influence of descriptive and injunctive peer norms on fruit consumption in adolescents

OBJECTIVES: While healthy eating patterns are of high importance in adolescence, most adolescents portray quite unhealthy eating behaviour. One reason for this may be that social norms among peers tend to be unsupportive of healthy eating. The current study investigates whether communicating health-promoting descriptive and injunctive norms influences adolescents' intended and actual fruit consumption. DESIGN: The study employed an experimental prospective design. METHODS: A norm message manipulation (descriptive vs. injunctive vs. no-norm control) was administered to high school students, after which fruit intake intention (N = 96) was assessed. At follow-up, actual fruit intake over 2 days (N = 80) was recorded. RESULTS: Adolescents receiving the descriptive norm did not report higher fruit intake intentions than the control group, but did consume (borderline, p = .057) significantly more fruit in the following 2 days (2.3 portions per day) than the control condition (1.7 portion per day). Adolescents receiving the injunctive norm reported lower fruit intake intentions than the other two groups, but actual fruit consumption (1.5 portions per day) was similar to that of the control group. CONCLUSIONS: Health-promoting injunctive norms not only had no positive effects on fruit intake but actually caused a decrease in fruit intake intentions, indicating that injunctive norms may be vulnerable to reactance. A health-promoting descriptive norm was found to positively affect fruit intake in adolescents. No effect on fruit intake intention was found. Results show that simple single-sentence norm messages hold the potential to substantially influence health behaviour