Homophobia, heteronormativism and hegemonic masculinity : male same-sex intimate violence from the perspective of Brisbane service providers

Few studies have explored the problem of male same-sex intimate partner violence, especially in the context of Australia. Utilizing in-depth interviews with gay-friendly service providers in Brisbane, the research presented in this article sought to ascertain whether (a) intimate partner violence occurs in male same-sex intimate relationships, (b)if so, what form this violence takes,(c) what contextual triggers underpin this violence,(d) what barriers victims face in exiting abusive relationships and seeking support, and (e) what services are available and appropriate to the needs of men in violent intimate relationships with other men. Results suggest that the prevalence, types and contextual triggers of violence in male same-sex relationships parallel abuse in opposite-sex relationships. Heteronormativism, homophobia, and its close association with hegemonic masculinity, however, emerge as features unique to the male same-sex intimate partner violence experience.

Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors

Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18-76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission.

Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells

High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

In vitro cultivation of adult human chondrocytes : importance of culture system, oxygen and zonal differences

Articular cartilage exhibits limited intrinsic regenerative capacity and focal tissue defects can lead to the development of osteoarthritis (OA), a painful and debilitating loss of cartilage tissue. In Australia, 1.4 million people are affected by OA and its prevalence is increasing in line with current demographics. As treatment options are limited, new therapeutic approaches are being investigated including biological resurfacing of joints with tissue-engineered cartilage. Despite some progress in the field, major challenges remain to be addressed for large scale clinical success. For example, large numbers of chondrogenic cells are required for cartilage formation, but chondrocytes lose their chondrogenic phenotype (dedifferentiate) during in vitro propagation. Additionally, the zonal organization of articular cartilage is critical for normal cartilage function, but development of zonal structure has been largely neglected in cartilage repair strategies. Therefore, we hypothesised that culture conditions for freshly isolated human articular chondrocytes from non-OA and OA sources can be improved by employing microcarrier cultures and a reduced oxygen environment and that oxygen is a critical factor in the maintenance of the zonal chondrocyte phenotype. Microcarriers have successfully been used to cultivate bovine chondrocytes, and offer a potential alternative for clinical expansion of human chondrocytes. We hypothesised that improved yields can be achieved by propagating human chondrocytes on microcarriers. We found that cells on microcarriers acquired a flattened, polygonal morphology and initially proliferated faster than monolayercultivated cells. However, microcarrier cultivation over four weeks did not improve growth rates or the chondrogenic potential of non-OA and OA human articular chondrocytes over conventional monolayer cultivation. Based on these observations, we aimed to optimise culture conditions by modifying oxygen tension, to more closely reflect the in vivo environment. We found that propagation at 5% oxygen tension (moderate hypoxia) did not improve proliferation or redifferentiation capacity of human osteoarthritic chondrocytes. Moderate hypoxia increased the expression of chondrogenic markers during redifferentiation. However, osteoarthritic chondrocytes cultivated on microcarriers exhibited lower expression levels of chondrogenic surface marker proteins and had at best equivalent redifferentiation capacities compared to monolayer-cultured cells. This suggests that monolayer culture with multiple passaging potentially selects for a subpopulation of cells with higher differentiation capacity, which are otherwise rare in osteoarthritic, aged cartilage. However, fibroblastic proteins were found to be highly expressed in all cultures of human osteoarthritic chondrocytes indicating the presence of a high proportion of dedifferentiated, senescent cells with a chondrocytic phenotype that was not rescued by moderate hypoxia. The different zones of cartilage support chondrocyte subpopulations, which exhibit characteristic protein expression and experience varying oxygen tensions. We, therefore, hypothesised that oxygen tension affects the zonal marker expression of human articular chondrocytes isolated from the different cartilage layers. We found that zonal chondrocytes maintained these phenotypic differences during in vitro cultivation. Low oxygen environments favoured the expression of the zonal marker proteoglycan 4 in superficial cells, most likely through the promotion of chondrogenesis. The putative zonal markers clusterin and cartilage intermediate layer protein were found to be expressed by all subpopulations of human osteoarthritic chondrocytes ex vivo and, thus, may not be reliable predictors of in vitro stratification using these clinically relevant cells. The findings in this thesis underline the importance of considering low oxygen conditions and zonal stratification when creating native-like cartilaginous constructs. We have not yet found the right cues to successfully cultivate clinically-relevant human osteoarthritic chondrocytes in vitro. A more thorough understanding of chondrocyte biology and the processes of chondrogenesis are required to ensure the clinical success of cartilage tissue engineering.

Weaving yarns : the lived experience of Indigenous Australians with adult-onset disability in Brisbane

Indigenous Australians have lower levels of health than mainstream Australians and (as far as statistics are able to indicate) higher levels of disability, yet there is little information on Indigenous social and cultural constructions of disability or the Indigenous experience of disability. This research seeks to address these gaps by using an ethnographic approach, couched within a critical medical anthropology (CMA) framework and using the “three bodies” approach, to study the lived experience of urban Indigenous people with an adult-onset disability. The research approach takes account of the debate about the legitimacy of research into Indigenous Australians, Foucault‟s governmentality, and the arguments for different models of disability. The possibility of a cultural model of disability is raised. After a series of initial interviews with contacts who were primarily service providers, more detailed ethnographic research was conducted with three Indigenous women in their homes and with four groups of Indigenous women and men at an Indigenous respite centre. The research involved multiple visits over a period extending more than two years, and the establishment of relationships with all participants. An iterative inductive approach utilising constant comparison (i.e. a form of grounded theory) was adopted, enabling the generation and testing of working hypotheses. The findings point to the lack of an Indigenous construct of disability, related to the holistic construction of health among Indigenous Australians. Shame emerges as a factor which affects the way that Indigenous Australians respond to disability, and which operates in apparent contradiction to expectations of community support. Aspects of shame relate to governmentality, suggesting that self-disciplinary mechanisms have been taken up and support the more obvious exertion of government power. A key finding is the strength of Indigenous identity above and beyond other forms of identification, e.g. as a person with a disability, expressed in forms of resistance by individuals and service providers to the categories and procedures of the mainstream. The implications of a holistic construction of health are discussed in relation to the use of CMA, the interpretation of the “three bodies”, governmentality and resistance. The explanatory value of the concept of sympatricity is discussed, as is the potential value of a cultural model of disability which takes into account the cultural politics of a defiant Indigenous identity.

Crosstalk between developmental and tumour-specific signalling pathways : kallikrein-related serine peptidases and nodal in prostrate cancer

Prostate cancer is an important male health issue. The strategies used to diagnose and treat prostate cancer underscore the cell and molecular interactions that promote disease progression. Prostate cancer is histologically defined by increasingly undifferentiated tumour cells and therapeutically targeted by androgen ablation. Even as the normal glandular architecture of the adult prostate is lost, prostate cancer cells remain dependent on the androgen receptor (AR) for growth and survival. This project focused on androgen-regulated gene expression, altered cellular differentiation, and the nexus between these two concepts. The AR controls prostate development, homeostasis and cancer progression by regulating the expression of downstream genes. Kallikrein-related serine peptidases are prominent transcriptional targets of AR in the adult prostate. Kallikrein 3 (KLK3), which is commonly referred to as prostate-specific antigen, is the current serum biomarker for prostate cancer. Other kallikreins are potential adjunct biomarkers. As secreted proteases, kallikreins act through enzyme cascades that may modulate the prostate cancer microenvironment. Both as a panel of biomarkers and cascade of proteases, the roles of kallikreins are interconnected. Yet the expression and regulation of different kallikreins in prostate cancer has not been compared. In this study, a spectrum of prostate cell lines was used to evaluate the expression profile of all 15 members of the kallikrein family. A cluster of genes was co-ordinately expressed in androgenresponsive cell lines. This group of kallikreins included KLK2, 3, 4 and 15, which are located adjacent to one another at the centromeric end of the kallikrein locus. KLK14 was also of interest, because it was ubiquitously expressed among the prostate cell lines. Immunohistochemistry showed that these 5 kallikreins are co-expressed in benign and malignant prostate tissue. The androgen-regulated expression of KLK2 and KLK3 is well-characterised, but has not been compared with other kallikreins. Therefore, KLK2, 3, 4, 14 and 15 expression were all measured in time course and dose response experiments with androgens, AR-antagonist treatments, hormone deprivation experiments and cells transfected with AR siRNA. Collectively, these experiments demonstrated that prostatic kallikreins are specifically and directly regulated by the AR. The data also revealed that kallikrein genes are differentially regulated by androgens; KLK2 and KLK3 were strongly up-regulated, KLK4 and KLK15 were modestly up-regulated, and KLK14 was repressed. Notably, KLK14 is located at the telomeric end of the kallikrein locus, far away from the centromeric cluster of kallikreins that are stimulated by androgens. These results show that the expression of KLK2, 3, 4, 14 and 15 is maintained in prostate cancer, but that these genes exhibit different responses to androgens. This makes the kallikrein locus an ideal model to investigate AR signalling. The increasingly dedifferentiated phenotype of aggressive prostate cancer cells is accompanied by the re-expression of signalling molecules that are usually expressed during embryogenesis and foetal tissue development. The Wnt pathway is one developmental cascade that is reactivated in prostate cancer. The canonical Wnt cascade regulates the intracellular levels of β-catenin, a potent transcriptional co-activator of T-cell factor (TCF) transcription factors. Notably, β-catenin can also bind to the AR and synergistically stimulate androgen-mediated gene expression. This is at the expense of typical Wnt/TCF target genes, because the AR:β-catenin and TCF:β-catenin interactions are mutually exclusive. The effect of β-catenin on kallikrein expression was examined to further investigate the role of β-catenin in prostate cancer. Stable knockdown of β-catenin in LNCaP prostate cancer cells attenuated the androgen-regulated expression of KLK2, 3, 4 and 15, but not KLK14. To test whether KLK14 is instead a TCF:β-catenin target gene, the endogenous levels of β-catenin were increased by inhibiting its degradation. Although KLK14 expression was up-regulated by these treatments, siRNA knockdown of β-catenin demonstrated that this effect was independent of β-catenin. These results show that β-catenin is required for maximal expression of KLK2, 3, 4 and 15, but not KLK14. Developmental cells and tumour cells express a similar repertoire of signalling molecules, which means that these different cell types are responsive to one another. Previous reports have shown that stem cells and foetal tissues can reprogram aggressive cancer cells to less aggressive phenotypes by restoring the balance to developmental signalling pathways that are highly dysregulated in cancer. To investigate this phenomenon in prostate cancer, DU145 and PC-3 prostate cancer cells were cultured on matrices pre-conditioned with human embryonic stem cells (hESCs). Soft agar assays showed that prostate cancer cells exposed to hESC conditioned matrices had reduced clonogenicity compared with cells harvested from control matrices. A recent study demonstrated that this effect was partially due to hESC-derived Lefty, an antagonist of Nodal. A member of the transforming growth factor β (TGFβ) superfamily, Nodal regulates embryogenesis and is re-expressed in cancer. The role of Nodal in prostate cancer has not previously been reported. Therefore, the expression and function of the Nodal signalling pathway in prostate cancer was investigated. Western blots confirmed that Nodal is expressed in DU145 and PC-3 cells. Immunohistochemistry revealed greater expression of Nodal in malignant versus benign glands. Notably, the Nodal inhibitor, Lefty, was not expressed at the mRNA level in any prostate cell lines tested. The Nodal signalling pathway is functionally active in prostate cancer cells. Recombinant Nodal treatments triggered downstream phosphorylation of Smad2 in DU145 and LNCaP cells, and stably-transfected Nodal increased the clonogencity of LNCaP cells. Nodal was also found to modulate AR signalling. Nodal reduced the activity of an androgen-regulated KLK3 promoter construct in luciferase assays and attenuated the endogenous expression of AR target genes including prostatic kallikreins. These results demonstrate that Nodal is a novel example of a developmental signalling molecule that is reexpressed in prostate cancer and may have a functional role in prostate cancer progression. In summary, this project clarifies the role of androgens and changing cellular differentiation in prostate cancer by characterising the expression and function of the downstream genes encoding kallikrein-related serine proteases and Nodal. Furthermore, this study emphasises the similarities between prostate cancer and early development, and the crosstalk between developmental signalling pathways and the AR axis. The outcomes of this project also affirm the utility of the kallikrein locus as a model system to monitor tumour progression and the phenotype of prostate cancer cells.

"Surviving" adolescence : apocalyptic and post-apocalyptic transformations in young adult fiction

This study, entitled "Surviving" Adolescence: Apocalyptic and post-apocalyptic transformations in young adult fiction‖, analyses how discourses surrounding the apocalyptic and post-apocalyptic are represented in selected young adult fiction published between 1997 and 2009. The term ―apocalypse‖ is used by current theorists to refer to an uncovering or disclosure (most often a truth), and ―post-apocalypse‖ means to be after a disclosure, after a revelation, or after catastrophe. This study offers a double reading of apocalyptic and post-apocalyptic discourses, and the dialectical tensions that are inherent in, and arise from, these discourses. Drawing on the current scholarship of children‘s and young adult literature this thesis uses post-structural theoretical perspectives to develop a framework and methodology for conducting a close textual analysis of exclusion, ‗un‘differentiation, prophecy, and simulacra of death. The combined theoretical perspectives and methodology offer new contributions to young adult fiction scholarship. This thesis finds that rather than conceiving adolescence as the endurance of a passing phase of a young person‘s life, there is a new trend emerging in young adult fiction that treats adolescence as a space of transformation essential to the survival of the young adult, and his/her community.

Generalised self-efficacy in relation to the life transitions of adult learners in a university setting : towards a narrative constructivist model of self-regulation

This paper demonstrates a model of self-regulation based on a qualitative research project with adult learners undertaking an undergraduate degree. The narrative about the participant’s life transitions, co-constructed with the researcher, yielded data about their generalised self-efficacy and resulted in a unique self-efficacy narrative for each participant. A model of self-regulation is proposed with potential applications for coaching, counselling and psychotherapy. A narrative method was employed to construct narratives about an individual’s self-efficacy in relation to their experience of learning and life transitions. The method involved a cyclical and iterative process using qualitative interviews to collect life history data from participants. In addition, research participants completed reflective homework tasks, and this data was included in the participant’s narratives. A highly collaborative method entailed narratives being co-constructed by researcher and research participants as the participants were guided in reflecting on their experience in relation to learning and life transitions; the reflection focused on behaviour, cognitions and emotions that constitute a sense of self-efficacy. The analytic process used was narrative analysis, in which life is viewed as constructed and experienced through the telling and retelling of stories and hence the analysis is the creation of a coherent and resonant story. The method of constructing self-efficacy narratives was applied to a sample of mature aged students starting an undergraduate degree. The research outcomes confirmed a three-factor model of self-efficacy, comprising three interrelated stages: initiating action, applying effort, and persistence in overcoming difficulties. Evaluation of the research process by participants suggested that they had gained an enhanced understanding of self-efficacy from their participation in the research process, and would be able to apply this understanding to their studies and other endeavours in the future. A model of self-regulation is proposed as a means for coaches, counsellors and psychotherapists working from a narrative constructivist perspective to assist clients facing life transitions by helping them generate selfefficacious cognitions, emotions and behaviour.

Gender equality in national politics : the views of Australian male politicians

Studies of gender and politics have typically been studies of women and politics. In contrast, this paper places men at the centre of its inquiry by drawing on interviews with 15 current federal male politicians. Of concern is exploring the ways in which men conceptualise the question of gender equity in the Australian parliament. Three frameworks are identified in the men's narratives. These are that the parliament is a masculinised space but that this is unavoidable; that the parliament is now feminised and women are advantaged; and that the parliament is gender neutral and gender is irrelevant. It is argued that collectively these framing devices operate to mask the many constraints which exist to marginalise women from political participation and undermine attempts to address women's political disadvantage as political participants. The paper concludes by highlighting the significance of the paper beyond the Australian context and calling for further research which names and critiques political men and their discourses on gender and parliamentary practices and processes.

Adult human articular chondrocytes in a microcarrier-based culture system : expansion and redifferentiation

xpanding human chondrocytes in vitro while maintaining their ability to form cartilage remains a key challenge in cartilage tissue engineering. One promising approach to address this is to use microcarriers as substrates for chondrocyte expansion. While microcarriers have shown beneficial effects for expansion of animal and ectopic human chondrocytes, their utility has not been determined for freshly isolated adult human articular chondrocytes. Thus, we investigated the proliferation and subsequent chondrogenic differentiation of these clinically relevant cells on porous gelatin microcarriers and compared them to those expanded using traditional monolayers. Chondrocytes attached to microcarriers within 2 days and remained viable over 4 weeks of culture in spinner flasks. Cells on microcarriers exhibited a spread morphology and initially proliferated faster than cells in monolayer culture, however, with prolonged expansion they were less proliferative. Cells expanded for 1 month and enzymatically released from microcarriers formed cartilaginous tissue in micromass pellet cultures, which was similar to tissue formed by monolayer-expanded cells. Cells left attached to microcarriers did not exhibit chondrogenic capacity. Culture conditions, such as microcarrier material, oxygen tension, and mechanical stimulation require further investigation to facilitate the efficient expansion of clinically relevant human articular chondrocytes that maintain chondrogenic potential for cartilage regeneration applications.