http://hdl.handle.net/11343/159 Sat, 19 Jan 2019 20:10:30 GMT 2019-01-19T20:10:30Z http://hdl.handle.net/11343/220075 The sociology of the chick lit of Anita Heiss Morgan, Fiannuala Wiradjuri woman, Anita Heiss, is arguably one of the first Australian authors of popular fiction. Since 2007, she has published across a diversity of genres including chick lit, contemporary women’s fiction, romance, memoir and children’s literature. A focus on the political characterises her work; and her identity as an author is both supplemented and complemented by her roles as an academic, activist and public intellectual. Heiss has discussed genre as a means of targeting specific audiences that may be less engaged with Indigenous affairs, and positions her novels as educative but not didactic. There remains, however, some ambivalence about the significance of the role that genre plays in her literature as well as for the diverse and differentiated audience that she attracts. The aims of this thesis then are two-fold: firstly, to present a complication of academic conceptions of genre, then to use this discussion to explore the social significance of Heiss’ literature. My focus is Heiss’ first four chick lit novels: Not Meeting Mr Right (2007), Avoiding Mr Right (2008), Manhattan Dreaming (2010) and Paris Dreaming (2011). Scholarship in the field leans toward an understanding that the racial politics of non-white articulations of the chick lit genre are invariably incompatible with the basic formula of chick lit texts. My thesis proposes a methodological shift from the dominant mode of ideological analysis to one that is largely focused on reader response. This approach is influenced by Bourdieu’s sociological approach to literature and adapts his multi-tiered analysis to account for the author, the text and the reader. Still implicit in academic writing on chick lit is an argument for formula as constitutive of the genre, this thesis negates this position and follows John Frow’s (2006) understanding of genre as an interpretive frame. This holistic approach allows for a complication of pessimistic readings that reproduce racially thematised chick lit as deviant or politically problematic. I pursue the question of how Heiss’ writing functions in the public sphere, as well as undertaking broader enquiry into the significance of genre for both author and reader. Heiss’ readership is constituted by committed readers of romance and chick lit as well as politically engaged readers that are attracted to Heiss’ dual authorial persona; and, both groups bring radically distinct expectations to bear on these texts. Through analysis of online reviews and surveys conducted with users of the book reviewing website Goodreads, I complicate the understanding of genre as a cogent interpretative frame, and deploy this discussion to explore the social significance of Heiss’ literature. © 2018 Fiannuala Morgan Mon, 01 Jan 2018 00:00:00 GMT http://hdl.handle.net/11343/220075 2018-01-01T00:00:00Z http://hdl.handle.net/11343/220070 Unravelling organ-specific MAIT cell response using a mouse model of systemic bacterial infection Shi, Mai Mucosal-associated invariant T (MAIT) cells are a subset of T cells defined by expression of a semi-invariant TCR and restriction to MHC-related protein-1 (MR1). MAIT cells recognize riboflavin (vitamin B2)-derived metabolites and may provide immune protection against certain riboflavin-synthesizing bacteria. However, the mechanisms and the organ-specific ability for MAIT cells’ in vivo antibacterial properties are not well understood. Using a systemic mouse infection model of Francisella tularensis live vaccine strain (LVS), this study aims to investigate MAIT cells responses and phenotypes in a range of organs throughout the infection. It was first verified that human MAIT cells could be activated by F. tularensis LVS metabolites using a well-established in vitro cellular T cell activation assay. Next, a rapid accumulation of MAIT cells was detected in the liver, lungs, spleen, kidneys, and blood during the early phase of F. tularensis LVS infection in mice. MAIT cells remained at a high number for a long period after reaching their peak expansion. The organ-specific MAIT cell phenotype and cytokine secretion properties were characterized during the infection course. Most MAIT cells in all the organs were similarly polarized to a Th1 phenotype and produced high levels of IFN-γ and TNF and a moderate level of GM-CSF, but a non-detectable level of IL-17. The liver and kidneys were notably the most competent organs for MAIT cells’ production of TNF and IFN-γ. In addition, mice lacking TNF, IFN-γ or GM-CSF were more susceptible to F. tularensis LVS infection, suggesting these cytokines, which are produced by MAIT cells as well as other cell types, are critical for the control of infection. Importantly, MR1-/- (MAIT cell-deficient) mice showed significantly higher bacterial loads in all the organs tested in the mid-to-late phase of infection compared to C57BL/6 mice, indicating that MAIT cells are critical for systemic clearance of F. tularensis LVS. Adoptive transfer of MAIT cells to C57BL/6 mice significantly protected the mice against fatal intraperitoneal F. tularensis LVS infection in an MR1- and number-dependent manner. The survival duration of severely immunocompromised Rag2-/-γC-/- mice under F. tularensis LVS infection could be significantly prolonged by transferring MAIT cells. Lastly, the administration of MAIT cell activating antigen 5-OP-RU with TLR9 agonist CpG led to a systemic MAIT cell expansion in mice and thereby protected the mice from F. tularensis LVS infection. To conclude, this study deepens our understanding of MAIT cells’ antibacterial function as well as the heterogeneity and plasticity of MAIT cells in different organs. It opens up possibilities for follow-up investigations into systemic MAIT cell responses and the development of vaccination methods targeting MAIT cells. © 2018 Mai Shi Mon, 01 Jan 2018 00:00:00 GMT http://hdl.handle.net/11343/220070 2018-01-01T00:00:00Z http://hdl.handle.net/11343/220049 Examination of key clinical, biological, psychological and social factors associated with post-pubertal anxiety in young people diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) Mohammadpoorshoorcheh, Elham Introduction: ADHD and anxiety are two common developmental mental health conditions that co-occur in 25% to 33% of young people with ADHD. There are associated functional impairments in these disorders across clinical, biological (e.g., working memory, IQ scores and blood pressure), psychological (e.g., language, emotion regulation and academic achievement) and social (e.g., social competence and positive illusory bias) domains, which may be more severe or ameliorated when they co-occur. It is important to understand and recognise these impairing associations of ADHD and post-pubertal anxiety across developmental stages in order to target them early with appropriate and effective therapy interventions. To date there are relatively few longitudinal datasets examining key risk factors associated with these comorbid conditions and more research is needed to investigate how post-pubertal anxiety influences the different domains of life of young people with ADHD (all presentations) from childhood through to adolescence. Methods: This thesis presents a three-year blinded follow-up evaluation of children with ADHD from pre- through to post-puberty, investigating those with and without post-puberty anxiety. At baseline, relevant demographic, clinical, and functional (biological, psychological and social) information was collected from clinically referred pre-pubertal participants with ADHD (all presentations) (N=419). After the pre-pubertal baseline assessment (Tanner stage 1) all participants were followed up three years later (Tanner stage 3-5). Given that 25% of the sample were not able to be re-assessed (N=104), 118 young people were recruited with ADHD and post-pubertal anxiety [84 (71%) treated with stimulant medication or atomoxetine] and 72 young people were recruited with ADHD alone (anxiety absent) [53 (74%) treated with stimulant medication or atomoxetine], both based on parent and the child report of anxiety. Due to subclinical anxiety features, 125 young people were precluded from the study. Groups were compared for clinical (ADHD- all presentations-, ODD/CD, anxiety and depressive disorders), biological (verbal/non-verbal IQ, verbal/spatial working memory and blood pressure (systolic & diastolic - postural), psychological (language, academic achievement, emotional regulation and emotional negativity/lability), and social (social competence and positive illusory bias) characteristics. Results: There was an increased total score in the parental self-report of their total tmental health symptoms in the group of young people with ADHD and post-pubertal anxiety. However, all the significant group differences remained when the parental self- report of their total symptoms was entered as a covariate. In the clinical domain, MDD, DD (DSM-5 persistent depressive disorder equivalent) and GAD significantly predicted ADHD and post-pubertal anxiety group membership. In the psychological domain, young people with ADHD and post-pubertal anxiety had a better performance in the spatial working memory task (e.g., a lower between search error total score and a better spatial working memory strategy score). This group of young people manifested worse emotion regulation abilities and increased emotional lability/negativity in comparison with the ADHD alone group. In contrast, positive illusory bias was ameliorated in young people with child defined ADHD and post- pubertal anxiety on the teacher minus child delinquent behaviour subscale of the Child Behaviour Checklist but there was an increased level of positive illusory bias in young people with parent defined ADHD and post-pubertal anxiety on the parent minus child anxious/depressed and thought problems subscales of the Child Behaviour Checklist. Discussion: The findings outlined in this thesis suggest post-pubertal anxiety in the ADHD population needs to be effectively managed through preserving the potential benefits of a better spatial working memory performance and a more realistic self- appraisal related to post-pubertal anxiety along with optimal management of the deleterious impairments of ADHD (all presentations), anxiety and depression. In addition, these results emphasise the necessity of recognising the differences and similarities between parent-reported child anxiety and child-reported anxiety through successive developmental stages. Future clinical and research directions are discussed. © 2018 Dr. Elham Mohammadpoorshoorcheh Tue, 01 Jan 2019 00:00:00 GMT http://hdl.handle.net/11343/220049 2019-01-01T00:00:00Z http://hdl.handle.net/11343/220001 New approaches to induce tolerance in autoantigen-specific memory T cells in type 1 diabetes Selck, Claudia Autoimmune disorders like type 1 diabetes (T1D) result from the failure of immune tolerance mechanisms. Antigen-specific therapy constitutes an attractive approach to re-establish a tolerant state but has so far not been successful in clinical settings. Importantly, treatment after the onset of autoimmunity is likely to be less effective due to established autoimmune responses and active inflammation in the islets. Moreover, a major hurdle might be the persistence of antigen-experienced islet-reactive T cells and the induction of tolerance in these memory cells is challenging. Hence, therapies intended to induce antigen-specific tolerance may need additional immunomodulatory treatments to be effective in individuals with established autoimmunity. Here, we aimed to identify a combination of interventions that induces tolerance in antigen-specific memory T cells. For this study, we generated non-obese diabetic (NOD) mice with tetracycline-regulated expression of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) in antigen presenting cells (TII mice) and tracked IGRP-specific CD8+ T cells using tetramer enrichment. Notably, while naïve IGRP-specific T cells are eliminated upon antigen expression, memory T cells are refractory to cell depletion. Interestingly, these memory T cells up-regulated several exhaustion markers in response to antigen exposure but showed no functional impairment. We hypothesized that combining short-term treatment with non-Fc-binding anti-CD3 F(ab’)2 and the co-stimulation blocker abatacept together with antigen expression might induce effective tolerance in TII mice. However, after initial depletion of antigen-experienced IGRP-specific cells by anti-CD3 F(ab’)2, these cells re-expanded and were still functional. Thus, our combination approach has only limited efficacy in established autoimmunity. Combination therapies of antigen-specific therapies with agents that support the induction of complete T cell exhaustion might be more successful and should be tested in future studies. © 2018 Dr. Claudia Selck Mon, 01 Jan 2018 00:00:00 GMT http://hdl.handle.net/11343/220001 2018-01-01T00:00:00Z