Limbal mesenchymal stromal cells (L-MSC) display immunosuppressive properties across donor and species boundaries

Purpose: We have evaluated the immunosuppressive properties of L-MSC with the view to using these cells in allogeneic cell therapies for corneal disorders. We hypothesized that L-MSC cultures would suppress T-cell activation, in a similar way to those established from human bone marrow (BM-MSC). Methods: MSC cultures were established from the limbal stroma of cadaveric donor eye tissue (up to 1 week postmortem) using either conventional serum-supplemented growth medium or a commercial serum-free medium optimized for bone marrow derived MSC (MesenCult-XF system). The MSC phenotype was examined by flow cytometry according to current and emerging markers for human MSC. Immunosuppressive properties were assessed using a mixed lymphocyte reaction (MLR) assay, whereby the white cell fraction from two immunologically incompatible blood donors are cultured together in direct contact with growth arrested MSC. T-cell activation (proliferation) was measured by uptake of tritiated thymidine. Human L-MSC were tested in parallel with human BM-MSC and rabbit L-MSC. Human and rabbit L-MSC were also tested for their ability to stimulate the growth of limbal epithelial (LE) cells in colony formation assays (for both human as well as rabbit LE cells). Results: L-MSC cultures were >95% negative for CD34, CD45 and HLA-DR and positive for CD73, CD90, CD105 and HLA-ABC. Modest levels (30%) of CD146 expression were observed for L-MSC cultures grown in serum-supplemented growth medium, but not those grown in MesenCult-XF. All MSC cultures derived from both human and rabbit tissue suppressed T-cell activation to varying degrees according to culture technique and species (MesenCult-XF >> serum-fed cultures, rabbit L-MSC >> human L-MSC). All L-MSC stimulated colony formation by LE cells irrespectively of the combination of cell species used. Conclusions: L-MSC display immunosuppressive qualities, in addition to their established non-immunogenic cell surface marker profile, and stimulate LE cell growth in vitro across species boundaries. These results support the potential use of allogeneic or even xenogeneic L-MSC in the treatment of corneal disorders.

Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas

Background aims Mesenchymal stromal cells (MSCs) cultivated from the corneal limbus (L-MSCs) provide a potential source of cells for corneal repair. In the present study, we investigated the immunosuppressive properties of human L-MSCs and putative rabbit L-MSCs to develop an allogeneic therapy and animal model of L-MSC transplantation. Methods MSC-like cultures were established from the limbal stroma of human and rabbit (New Zealand white) corneas using either serum-supplemented medium or a commercial serum-free MSC medium (MesenCult-XF Culture Kit; Stem Cell Technologies, Melbourne, Australia). L-MSC phenotype was examined by flow cytometry. The immunosuppressive properties of L-MSC cultures were assessed using mixed leukocyte reactions. L-MSC cultures were also tested for their ability to support colony formation by primary limbal epithelial (LE) cells. Results Human L-MSC cultures were typically CD34−, CD45− and HLA-DR− and CD73+, CD90+, CD105+ and HLA-ABC+. High levels (>80%) of CD146 expression were observed for L-MSC cultures grown in serum-supplemented medium but not cultures grown in MesenCult-XF (approximately 1%). Rabbit L-MSCs were approximately 95% positive for major histocompatibility complex class I and expressed lower levels of major histocompatibility complex class II (approximately 10%), CD45 (approximately 20%), CD105 (approximately 60%) and CD90 (<10%). Human L-MSCs and rabbit L-MSCs suppressed human T-cell proliferation by up to 75%. Conversely, L-MSCs from either species stimulated a 2-fold to 3-fold increase in LE cell colony formation. Conclusions L-MSCs display immunosuppressive qualities in addition to their established non-immunogenic profile and stimulate LE cell growth in vitro across species boundaries. These results support the potential use of allogeneic L-MSCs in the treatment of corneal disorders and suggest that the rabbit would provide a useful pre-clinical model.

Why ADR must be a mandatory subject in the law degree - the academy

The profession of law is deeply steeped in tradition and conservatism. The content and pedagogy employed in law faculties across Australia is similarly steeped in tradition and conservatism. Indeed, the practice of law and our institutions of legal education are in a relationship of mutual influence; a dénouement which preserves the best aspects of our common law legal system, but also leaves the way we educate, practice, and think about the role of law, resistant to change. In this article, we lay down a challenge to legal education orthodoxy and a call to arms for legal academic progressivists. It is our simple argument that alternative dispute resolution should be a compulsory, stand alone subject in the law degree. There has been traditional pushback against the notion that alternative dispute resolution should have a place amongst black letter law subjects in the legal curriculum. This position cannot be maintained in the modern day legal climate. We put forward ten simple arguments as to why every law student should be exposed to a semester long course of ADR instruction. With respect to relationships of mutual influence, whether legal education should assimilate the practise of law, or shape the practise of law makes no difference here. Both views necessitate the inclusion of ADR as a compulsory subject in the law degree.

Peer review of teaching practice and resources : exploring new spaces to embrace cultural change

The implementation of systematic peer review as a professional development activity, and as a support for educational design activities is under-utilised in many Australian higher education institutions. This case study reports on the first stages of planning and implementation of an institution-wide project to enhance teaching and learning quality at a remote and regional university, where one of the major strategies for improvement is peer review. Through a systematic process of staff engagement in peer review, within and from outside the organisation, a substantial change in flexible learning is envisaged. A mix of new and different learning spaces are to be used in the project, including blended learning spaces for academic development. This paper describes the research framework that will guide the peer review process and examines the early findings of the design-based research. Leadership, awareness raising and development of a supportive community of inquiry are seen as key components for successful implementation of peer review. In addition, unique contextual elements add to the complexity of designing for transformative change within such a relatively new organization.

Plasmodium vivax malaria incidence over time and its association with temperature and rainfall in four counties of Yunnan Province, China

Background Transmission of Plasmodium vivax malaria is dependent on vector availability, biting rates and parasite development. In turn, each of these is influenced by climatic conditions. Correlations have previously been detected between seasonal rainfall, temperature and malaria incidence patterns in various settings. An understanding of seasonal patterns of malaria, and their weather drivers, can provide vital information for control and elimination activities. This research aimed to describe temporal patterns in malaria, rainfall and temperature, and to examine the relationships between these variables within four counties of Yunnan Province, China. Methods Plasmodium vivax malaria surveillance data (1991–2006), and average monthly temperature and rainfall were acquired. Seasonal trend decomposition was used to examine secular trends and seasonal patterns in malaria. Distributed lag non-linear models were used to estimate the weather drivers of malaria seasonality, including the lag periods between weather conditions and malaria incidence. Results There was a declining trend in malaria incidence in all four counties. Increasing temperature resulted in increased malaria risk in all four areas and increasing rainfall resulted in increased malaria risk in one area and decreased malaria risk in one area. The lag times for these associations varied between areas. Conclusions The differences detected between the four counties highlight the need for local understanding of seasonal patterns of malaria and its climatic drivers.

Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts

Haematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs) or osteoblasts. Sorted Lineage− Sca-1+ c-kit+ (LSK) haematopoietic stem/progenitor cells (HPC) demonstrated proliferative capacity on both stromal monolayers with the greatest expansion of LSK shown in cultures supported by osteoblast monolayers. After transplantation, both types of bulk-expanded cultures were capable of engrafting and repopulating lethally irradiated primary and secondary murine recipients. LSKs co-cultured on MSCs showed comparable, but not superior, reconstitution ability to that of freshly isolated LSKs. Surprisingly, however, osteoblast co-cultured LSKs showed significantly poorer haematopoietic reconstitution compared to LSKs co-cultured on MSCs, likely due to a delay in short-term reconstitution. We demonstrated that stromal monolayers can be used to maintain, but not expand, functional HSCs without a need for additional haematopoietic growth factors. We also demonstrated that despite apparently superior in vitro performance, co-injection of bulk cultures of osteoblasts and LSKs in vivo was detrimental to recipient survival and should be avoided in translation to clinical practice.

Anglican boarding school a hotbed of sexual punishment

THE little Anglican boarding school of St Barnabas, in the misty mountain town of Ravenshoe, north Queensland, was allegedly a hotbed of physical and sexual abuse in the 1960s. North Queensland Bishop Bill Ray has confirmed the diocese has few files about the school -- which was closed mid-term in 1990 -- with suspicions they were dumped "down a well or an old mine shaft" in the district A history of brutal physical punishment and sexual abuse at the school dating from the 1960s is now emerging. Headmaster Robert Waddington, who arrived at the school from England to be headmaster in 1961, dished out daily canings to many of his young students and then allegedly raped some behind closed doors in his room or the sick bay, which were next to each other. Former St Barnabas student Bim Atkinson, now 58, and two other former students have levelled allegations against the man they called "the Wadd".

Accused cleric built reputation at small school in Australia

The little Anglican boarding school of St Barnabas, in the mountain town of Ravenshoe, north Queensland, was where Robert Waddington built his reputation as an educationalist. He was headmaster there from 1961-70, but a growing number of former pupils are now coming forward to say they were subjected to sexual and physical abuse by him. Bim Atkinson, 58, said that his ordeal began after he was sent to the school and joined the choir. “I was absolutely petrified of the man,” Mr Atkinson recalls. “After I joined the choir, the abuse started. He would tell me to go to the sickbay, which had a connecting door to his bedroom and then I would end up in his room.”

Church officials believed claims were true

FORMER Anglican church officials have admitted they believed a former school headmaster had abused children at a north Queensland boarding school, despite telling a victim during mediation over a compensation payout that his allegations were not proven. For more than six years, Anglican officials dismissed the allegations of Queensland pensioner Bim Atkinson that he had been sexually abused between 1964 and 1968 by the Reverend Robert Waddington, the former headmaster of St Barnabas boarding school in Ravenshoe, on the Atherton Tablelands. In documents and letters obtained by The Weekend Australian, senior church officials in England and Australia told Mr Atkinson, now 59, that Waddington had denied the allegations and his claims were "not proven", despite an internal investigation. Mr Atkinson made his first complaint in 1999 -- when Waddington was living in retirement in York -- but dropped the case after being told the former school principal was near death after surgery for throat cancer. Waddington did not die until 2007. In 2004, Mr Atkinson refiled his complaint, with church officials telling him the allegations were "not proven" and did not warrant another investigation.

Pockets of Change : Adaptation and Cultural Transition

Pockets of Change collects fourteen essays that address issues of cultural adaptation and transition in the Arts. Based on insights into a range of primary texts and cultural practices—from visual art to film, from literature to theatre—these essays investigate the ways in which traditions, art-forms, cultures and ethics adapt to challenge established boundaries.

Developing a culture to support peer review of teaching in higher education

This presentation addresses issues related to leadership, academic development and scholarship of teaching and learning, and highlights research funded by the Australian Office of Learning and Teaching (OLT) designed to embed and sustain peer review of teaching within the culture of 5 Australian universities: Queensland University of Technology, University of Technology, Sydney, University of Adelaide, Curtin University, and Charles Darwin University. Peer review of teaching in higher education will be emphasised as a professional process for providing feedback on teaching and learning practice, which if sustained, can become an effective ongoing strategy for academic development (Barnard et al, 2011; Bell, 2005; Bolt and Atkinson, 2010; McGill & Beaty 2001, 1992; Kemmis & McTaggart, 2000). The research affirms that using developmental peer review models (Barnard et al, 2011; D'Andrea, 2002; Hammersley-Fletcher & Orsmond, 2004) can bring about successful implementation, especially when implemented within a distributive leadership framework (Spillane & Healey, 2010). The project’s aims and objectives were to develop leadership capacity and integrate peer review as a cultural practice in higher education. The research design was a two stage inquiry process over 2 years. The project began in July 2011 and encompassed a development and pilot phase followed by a cascade phase with questionnaire and focus group evaluation processes to support ongoing improvement and measures of outcome. Leadership development activities included locally delivered workshops complemented by the identification and support of champions. To optimise long term sustainability, the project was implemented through existing learning and teaching structures and processes within the respective partner universities. Research outcomes highlight the fundamentals of peer review of teaching and the broader contextual elements of integration, leadership and development, expressed as a conceptual model for embedding peer review of teaching within higher education. The research opens a communicative space about introduction of peer review that goes further than simply espousing its worth and introduction. The conceptual model highlights the importance of development of distributive leadership capacity, integration of policies and processes, and understanding the values, beliefs, assumptions and behaviors embedded in an organizational culture. The presentation overviews empirical findings that demonstrate progress to advance peer review requires an ‘across-the-board’ commitment to embed change, and inherently demands a process that co-creates connection across colleagues, discipline groups, and the university sector. Progress toward peer review of teaching as a cultural phenomenon can be achieved and has advantages for academic staff, scholarship, teaching evaluation and an organisation, if attention is given to strategies that influence the contexts and cultures of teaching practice. Peer review as a strategy to develop excellence in teaching is considered from a holistic perspective that by necessity encompasses all elements of an educational environment and has a focus on scholarship of teaching. The work is ongoing and has implication for policy, research, teaching development and student outcomes, and has potential application world-wide.

Analysis of expressed sequence tags from Actinidia : Applications of a cross species EST database for gene discovery in the areas of flavor, health, color and ripening

Background Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have produced a collection of 132,577 expressed sequence tags (ESTs). Results The ESTs were derived mainly from four Actinidia species (A. chinensis, A. deliciosa, A. arguta and A. eriantha) and fell into 41,858 non redundant clusters (18,070 tentative consensus sequences and 23,788 EST singletons). Analysis of flavor and fragrance-related gene families (acyltransferases and carboxylesterases) and pathways (terpenoid biosynthesis) is presented in comparison with a chemical analysis of the compounds present in Actinidia including esters, acids, alcohols and terpenes. ESTs are identified for most genes in color pathways controlling chlorophyll degradation and carotenoid biosynthesis. In the health area, data are presented on the ESTs involved in ascorbic acid and quinic acid biosynthesis showing not only that genes for many of the steps in these pathways are represented in the database, but that genes encoding some critical steps are absent. In the convenience area, genes related to different stages of fruit softening are identified. Conclusion This large EST resource will allow researchers to undertake the tremendous challenge of understanding the molecular basis of genetic diversity in the Actinidia genus as well as provide an EST resource for comparative fruit genomics. The various bioinformatics analyses we have undertaken demonstrates the extent of coverage of ESTs for genes encoding different biochemical pathways in Actinidia.