Roles of the Immune Cytokine Environment on Clonal Growth of Murine and Human Tet2 Mutant Bone Marrow Progenitors: Implications for Myelodysplastic Syndromes

TET2 is a tumor suppressor gene that has been implicated in the epigenetic regulation of gene expression. Inactivating TET2 mutations are common in MDS. These mutations may contribute to early clonal dominance and myeloid transformation, although the exact mechanisms remain to be elucidated. Common to the environment of MDS are elevations in cytokines, such as TNFα and IFN-γ. It was hypothesized that inflammatory cytokines TNF-α and IFN-γ may promote clonal expansion of TET2 mutant progenitors. Adult (10-14 weeks-old) Tet2 wild type (+/+) and Tet2 mutant (-/-) C57BL/6 mice strains were chosen as a model system. Lineage negative cells (Lin-), enriched for hematopoietic stem and progenitor cells, were isolated from Tet2 +/+ and -/- bone marrow and cultured in the absence or presence of varying concentrations of TNFα or IFN-γ in methylcellulose colony formation assays and long term cell culture assays, over a period of 12 and 30 days respectively, and their colony growth, cell count, immunophenotype and resistance to apoptosis were examined. Where indicated, serial re-plating was performed. Expression of apoptotic regulators was assessed by qRT-PCR. In the triplicate experiments, starting with equal densities of Tet2 +/+ and -/- Lin- cells, Tet2 -/- Lin- cells displayed increased resistance to cytokine-induced growth suppression and superior colony forming ability over +/+ in the serial re-plating assays under stress of increasing TNFα or IFN γ. Tet2 -/- progenitors also displayed a lower apoptotic index compared to +/+ under stress of increasing TNFα, suggesting increased resistance to TNFα induced apoptosis. Transcriptional data showed low expression of Tnfr1, Fas and caspase 8, as well as a high expression of Bcl-2 and Iap1 in Tet2 -/- compared to +/+ under stress of TNFα. Tet2-/- also showed increased basal expression of endogenous TNFα mRNA compared to +/+. In the human colony growth assay, the clonal growth of TET2 mutant CFU-GM progenitors was enhanced at low TNFα concentrations. Conclusion: Mutations that promote resistance to environmental stem cell stressors are a known mechanism of clonal selection in aplastic anaemia and JAK2-mutant MPN and our findings suggest that this mechanism may be critical to clonal selection and dominance in MDS.

World heritage management and human rights

This book focuses on the balance between protecting human rights and protecting world heritage sites. It concerns itself with the idea that the management of heritage properties worldwide may fail to adequately respect traditional entitlements and rights of individuals and communities living within or being affected by changes in the use of these spaces. It also explores the concept that the international heritage field has limited knowledge and awareness of this challenge.

Exploring the influence of a science content course incorporating explicit nature of science and argumentation instruction on preservice primary teachers' views of nature of science

There exists a general consensus in the science education literature around the goal of enhancing students. and teachers. views of nature of science (NOS). An emerging area of research in science education explores NOS and argumentation, and the aim of this study was to explore the effectiveness of a science content course incorporating explicit NOS and argumentation instruction on preservice primary teachers. views of NOS. A constructivist perspective guided the study, and the research strategy employed was case study research. Five preservice primary teachers were selected for intensive investigation in the study, which incorporated explicit NOS and argumentation instruction, and utilised scientific and socioscientific contexts for argumentation to provide opportunities for participants to apply their NOS understandings to their arguments. Four primary sources of data were used to provide evidence for the interpretations, recommendations, and implications that emerged from the study. These data sources included questionnaires and surveys, interviews, audio- and video-taped class sessions, and written artefacts. Data analysis involved the formation of various assertions that informed the major findings of the study, and a variety of validity and ethical protocols were considered during the analysis to ensure the findings and interpretations emerging from the data were valid. Results indicated that the science content course was effective in enabling four of the five participants. views of NOS to be changed. All of the participants expressed predominantly limited views of the majority of the examined NOS aspects at the commencement of the study. Many positive changes were evident at the end of the study with four of the five participants expressing partially informed and/or informed views of the majority of the examined NOS aspects. A critical analysis of the effectiveness of the various course components designed to facilitate the development of participants‟ views of NOS in the study, led to the identification of three factors that mediated the development of participants‟ NOS views: (a) contextual factors (including context of argumentation, and mode of argumentation), (b) task-specific factors (including argumentation scaffolds, epistemological probes, and consideration of alternative data and explanations), and (c) personal factors (including perceived previous knowledge about NOS, appreciation of the importance and utility value of NOS, and durability and persistence of pre-existing beliefs). A consideration of the above factors informs recommendations for future studies that seek to incorporate explicit NOS and argumentation instruction as a context for learning about NOS.

Discrepancy between human resource research and practice : comparison of industrial/organisational psychologists and human resource practitioners' beliefs

There is a large and growing body of research to show that human resource (HR) practices affect individual performance, organisational productivity and organisational performance. Academic findings about effective HR practices, however, have not readily been adopted by practitioners. A variety of theoretical and practical explanations have been advanced about the research-practice gap. Research by Rynes, Colbert, and Brown (2002) suggested that the research-practice gap is due to a lack of knowledge, but the extent to which these findings apply to the Australian context is unknown. The sample consisted of 102 industrial/organisational (I/O) psychologists and 89 HR practitioners. The main aim of the present study was to replicate and extend the work of Rynes et al. by examining and comparing the knowledge of I/O psychologists and HR practitioners. It was found that overall I/O psychologists were better informed about HR research than HR practitioners; in particular, they were more knowledgeable about management practices and recruitment and selection. In both groups, of the five content areas examined (Management Practices; General Employment Practices; Training and Development; Recruitment and Selection; and Compensation and Benefits), the greatest gaps were in Recruitment and Selection.

The measurement of broadband ultrasonic attenuation in cancellous bone-a review of the science and technology

The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone at the calcaneus was first described in 1984. The assessment of osteoporosis by BUA has recently been recognized by Universities UK, within its EurekaUK book, as being one of the “100 discoveries and developments in UK Universities that have changed the world” over the past 50 years, covering the whole academic spectrum from the arts and humanities to science and technology. Indeed, BUA technique has been clinically validated and is utilized worldwide, with at least seven commercial systems providing calcaneal BUA measurement. However, a fundamental understanding of the dependence of BUA upon the material and structural properties of cancellous bone is still lacking. This review aims to provide a science- and technology-orientated perspective on the application of BUA to the medical disease of osteoporosis.

Frontiers in Materials Science and Technology

This special issue aims to provide up-to-date knowledge and the latest scientific concepts and technological developments in the processing, characterization, testing, mechanics, modeling and applications of a broad range of advanced materials. The many contributors, from Denmark, Germany, UK, Iran, Saudi Arabia, Malaysia, Japan, the People’s Republic of China, Singapore, Taiwan, USA, New Zealand and Australia, present a wide range of topics including: nanomaterials, thin films and coatings, metals and alloys, composite materials, materials processing and characterization, biomaterials and biomechanics, and computational materials science and simulation. The work will therefore be of great interest to a broad spectrum of researchers and technologists.

Teaching and learning science and mathematics through technology practice

In this chapter we review studies of the engagement of students in design projects that emphasise integration of technology practice and the enabling sciences, which include physics and mathematics. We give special attention to affective and conceptual outcomes from innovative interventions of design projects. This is important work because of growing international concern that demand for professionals with technological expertise is increasing rapidly, while the supply of students willing to undertake the rigors of study in the enabling sciences is proportionally reducing (e.g., Barringtion, 2006; Hannover & Kessels, 2004; Yurtseven, 2002). The net effect is that the shortage in qualified workers is having a detrimental effect upon economic and social potential in Westernised countries (e.g., Department of Education, Science and Training [DEST], 2003; National Numeracy Review Panel and National Numeracy Review Secretarial, 2007; Yurtseven, 2002). Interestingly, this trend is reversed in developing economies including China and India (Anderson & Gilbride, 2003).

Science and subjectivity

Science has been under attack in the last thirty years, and recently a number of prominent scientists have been busy fighting back. Here, an argument is presented that the `science wars' stem from an unreasonably strict adherence to the reductive method on the part of science, but that weakening this stance need not imply a lapse into subjectivity. One possible method for formalising the description of non-separable, contextually dependent complex systems is presented. This is based upon a quantum-like approach.

Introduction of a short writing task to measure and develop academic literacy in first year health undergraduates

This paper describes an initiative in the Faculty of Health at the Queensland University of Technology, Australia, where a short writing task was introduced to first year undergraduates in four courses including Public Health, Nursing, Social Work and Human Services, and Human Movement Studies. Over 1,000 students were involved in the trial. The task was assessed using an adaptation of the MASUS Procedure (Measuring the Academic Skills of University Students) (Webb & Bonanno, 1994). Feedback to the students including MASUS scores then enabled students to be directed to developmental workshops targeting their academic literacy needs. Students who achieved below the benchmark score were required to attend academic writing workshops in order to obtain the same summative 10% that was obtained by those who had achieved above the benchmark score. The trial was very informative, in terms of determining task appropriateness and timing, student feedback, student use of support, and student perceptions of the task and follow-up workshops. What we learned from the trial will be presented with a view to further refinement of this initiative.

Ecological perspectives and wellness

Since the industrial revolution, the development of a lifestyle lived predominantly indoors has resulted in less contact with nature. Research over the last twenty years has gradually been identifying the human health benefits attributed to re-connecting with the natural environment. The significance of feeling connected to natural environments, families and friends are described as a foundational requirement for human health and wellbeing (Maller et al., 2008). Also, the early findings of Schultz‟s (2002) work indicated that by feeling connected to the natural world a person is more likely to be committed to positively interact with and protect the natural world. Research on young people has indicated that young people are even more disconnected from the natural world. Leading some writers to call this disconnection a crisis termed “Nature Deficit Disorder.” Participants (n = 131) from 1st year university Physical Education and Human Movement Studies were asked to complete two questionnaires the Connectedness to Nature scale (CNS) (Mayer & Frantz, 2004) and the New Ecological Paradigm Scale (NEP) (Dunlap, Van Liere, Mertig, & Jones, 2000). The NEP and CNS are two scales most commonly used to explore beliefs and feelings of connectedness to the natural world (Schultz, 2002). The NEP was developed over thirty years ago by Dunlap and Van Liere (1978) and originally termed the New Environmental Paradigm. The NEP is now the foremost International tool for measuring beliefs about the natural world (Dunlap, 2008). The CNS measures an individual‟s trait levels of emotional connection to the natural world. It is a relatively new tool for understanding ecological behaviour based on ecopsychology theory and employed to predict behaviour (Mayer and Frantz, 2004). Both questionnaires are based on a 1-5 scale (Strongly disagree to Strongly agree). By combing both scales the researchers aim to develop a snap shot of beliefs and emotional feelings towards the natural world and therefore an idea of intended behaviour. The two questionnaires were combined as one online survey with additional material asking for demographics and self assessments of type of leader included before the surveys. An email inviting outdoor leaders to participate was sent out to networks and interest groups. A basic descriptive statistical analysis was used to interpret data.