ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells

The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their "stem-ness" are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose-derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down-regulated in a randomized time-course study of osteogenically differentiated adipose-derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. © 2012 Wiley Periodicals, Inc.

Territorial strategies and regions

The notion of territorial strategy emerged in the 1990s and has become more and more popular since. It refers to that combination of factors purposely assembled by governments, private and public companies, universities, and industrial associations to exploit a specific geographic competitive advantage in order to boost economic growth through the development of entrepreneurial activity and innovation. Three factors are generally considered to be the building blocks of a territorial strategy: natural resources, human capital, and industrial capabilities. Natural resources derive from environ­ mental conditions and represent raw materials or land available in a region. The presence of natural resources characterizes the typology of an industry (related to tourism, oil, wood, fish, and so forth) that exists or could exist in a certain area. Human capital refers to the stock of competences available in a certain region resulting from education and work experience. Industrial capabilities relate to complex constructs of specialized expertise, the confidence to apply knowledge and skills in various contexts and under changing conditions, and an ability repeatedly to improve methods and processes in a specific industry.

Work related musculoskeletal disorders amongst therapists in physically demanding roles: Qualitative analysis of risk factors and strategies for prevention

Background Physiotherapy and occupational therapy are two professions at high risk of work related musculoskeletal disorders (WRMD). This investigation aimed to identify risk factors for WRMD as perceived by the health professionals working in these roles (Aim 1), as well as current and future strategies they perceive will allow them to continue to work in physically demanding clinical roles (Aim 2). Methods A two phase exploratory investigation was undertaken. The first phase included a survey administered via a web based platform with qualitative open response items. The second phase involved four focus group sessions which explored topics obtained from the survey. Thematic analysis of qualitative data from the survey and focus groups was undertaken. Results Overall 112 (34.3%) of invited health professionals completed the survey; 66 (58.9%) were physiotherapists and 46 (41.1%) were occupational therapists. Twenty-four health professionals participated in one of four focus groups. The risk factors most frequently perceived by health professionals included: work postures and movements, lifting or carrying, patient related factors and repetitive tasks. The six primary themes for strategies to allow therapists to continue to work in physically demanding clinical roles included: organisational strategies, workload or work allocation, work practices, work environment and equipment, physical condition and capacity, and education and training. Conclusions Risk factors as well as current and potential strategies for reducing WRMD amongst these health professionals working in clinically demanding roles have been identified and discussed. Further investigation regarding the relative effectiveness of these strategies is warranted.

Falls after discharge from hospital : is there a gap between older peoples' knowledge about falls prevention strategies and the research evidence?

Purpose: The aim of this study was to examine whether older people are prepared to engage in appropriate falls prevention strategies after discharge from hospital. Design and Methods We used a semi-structured interview to survey older patients about to be discharged from hospital and examined their knowledge regarding falls prevention strategies to utilize in the post-discharge period. The study was part of a prospective cohort study, nested within a larger, randomized controlled trial. Participants (n = 333) were asked to suggest strategies to reduce their falls risk at home after discharge, and their responses were compared with current reported research evidence for falls prevention interventions.  Results Participants’ strategies (n = 629) were classified into 7 categories: behavioral, support while mobilizing, approach to movement, physical environment, visual, medical, and activities or exercise. Although exercise has been identified as an effective falls risk reduction strategy, only 2.9% of participants suggested engaging in exercises. Falls prevention was most often conceptualized by participants as requiring 1 (35.4%) or 2 (40.8%) strategies for avoiding an accidental event, rather than engaging in sustained multiple risk reduction behaviors.  Implications Results demonstrate that older patients have low levels of knowledge about appropriate falls prevention strategies that could be used after discharge in spite of their increased falls risk during this period. Findings suggest that health care workers should design and deliver falls prevention education programs specifically targeted to older people who are to be discharged from hospital.

Strategies to engage academics in assuring graduate attributes

Assurance of learning (AoL) is a predominant feature in both quality assurance and quality enhancement in higher education. The process may be used for program development, and to inform external accreditation and evaluation bodies. However, there is an obvious challenge in trying to get academic staff to buy into the benefits of the AoL process. This project conducted an audit across 25 Australian Business Schools. The majority of those interviewed stated that academic staff considered AoL to be extra work and viewed the process as a box ticking exercise for external bodies rather than sound educational practice. A change management process is required to promote the necessary cultural change to embed AoL into practice. This paper showcases some of the educational leadership strategies that have been successfully implemented across Australia to foster staff engagement in the AoL process. These include: strong senior management commitment and leadership demonstrating a constant and high level drive for staff engagement until AoL becomes an institutional norm; developing leadership and champions among unit and program level staff, to share practices and promote the benefits that come from engaging in the process; providing professional development opportunities to discuss and resolve difficulties and tensions around AoL; demonstrating success and effectiveness by selling staff on the evidence that AoL makes a difference; and making the process inclusive with academics collaborating in the development and implementation of the process.

Instructing foreign language learners how to listen through metacognitive strategies : an empirical study

This study uses a mixed method approach to investigate the impact of metacognitive strategies instruction on listening comprehension. An experimental group (N = 30) of university students are guided through a process-approach pedagogy over one semester (10 weeks) in Iran. IELTS listening tests are used to track development of listening comprehension in participants who are then asked to complete a Metacognitive Awareness Listening Questionnaire (MALQ). The questionnaire examines students’ employment of metacognitive strategies in listening comprehension. Finally, interviews are used to explore students’ use of strategies in listening. Results indicate that participants develop listening comprehension, but no metacognitive awareness in listening. Students reported in the interviews that they use multiple strategies (cognitive and metacognitive) to approach listening comprehension.

Pragmatics, perceptions and strategies in Chinese college English learning

This study investigated Chinese College English students. perceptions of pragmatics, their pragmatic competence in selected speech acts, strategies they employed in acquiring pragmatic knowledge, as well as their general approach to learning English as a foreign language. The research was triggered by a national curriculum initiative that prioritizes the need for College English students to enhance their ability to use English effectively in different social interactions (Chinese College English Education and Supervisory Committee, 2007). The traditional "grammar-translation" and "examination-oriented" method is believed to have reduced Chinese College English students to what is dubbed "mute" and "deaf" language learners (Zhang, 2008; Zhao, 2009). Many students lack pragmatic knowledge on how to interpret discourse by relating utterances to their meanings, understanding the intention of language users, and how language is used in specific settings (Bachman & Palmer, 1996, 2010). There is an increasing body of literature on awareness-raising of the importance of pragmatic knowledge and strategies for classroom instruction. However, to date, researchers have tended to focus largely on the teaching of pragmatics, rather than on how students acquire pragmatic competence (Bardovi-Harlig & Dornyei, 1998; Du, 2004; Hou, 2007; Ruan, 2007; Schauer, 2009). It is this gap in the research that this study fills, with a focus on different types of pragmatic knowledge, learner perceptions of such knowledge, and learning strategies that College English students employ in the process of learning English in general, and pragmatics in particular. Three strands of theories of second language acquisition (Ellis, 1985, 1994): pragmatics (Levinson, 1983; Mey, 2001; Yule, 1996), intercultural communications (Kramsch, 1998; Samovar & Porter, 1997; Samovar, Porter & McDaniel, 2009) and English as a lingua franca (ELF) (Canagarajah, 2006; Firth, 1996; Pennycook, 2010) were employed to establish a conceptual framework for data collection and analyses. Key constructs derived from the three related theories helped to form a typology for a detailed examination and theorization of the empirical evidence gathered from different sources. Four research instruments: a questionnaire (N=237), Discourse Completion Tasks (DCTs) (N=55), focus group interviews (N=18), and a textbook tasks analysis were employed to collect data for this systematic inquiry. Data collected by different instruments were analyzed and compared by way of a triangulation to enhance its validity and reliability. Major findings derived from different sources highlighted that, although College English students were grammatically advanced language learners, they displayed limited pragmatic knowledge and a highly restricted repertoire of language learning strategies. The majority of the respondents, however, believed that pragmatic knowledge was as important as linguistic knowledge in the process of developing communicative competence for interaction in different contexts. It was argued that a combination of a less than sufficient English proficiency, limited knowledge of pragmatics, inadequate language materials and tasks, and a small stock of language learning strategies, were a major hindrance to effective learning and communication, resulting in pragmatic failures in many intercultural communication situations. As the first systematic study of how Chinese College English students learned pragmatics, the research provided a solid empirical base for developing a tentative model for the learning of pragmatics in a College English classroom in China and similar educational contexts. The model was strengthened by a unique combination of theories of pragmatics, intercultural communication and ELF. Findings from this research provided insights into how Chinese College English students perceived pragmatics in the English as foreign language (EFL) curriculum, the processes of learning, as well as strategies they utilized in developing linguistic and pragmatic knowledge and competence.

Domestic and international strategies in the Queensland wine industry

Purpose Over the past decade, the Queensland wine industry has experienced a greater percentage growth than the Australian national average. The aim of the research undertaken for this article is to identify specific national and international strategies that have allowed the industry to achieve this level of growth. Design/methodology/approach The study involved a quantitative survey of all Queensland wineries at the time (n=101), using a five-point Likert-scaled questionnaire with questions developed from the literature, together with a small-scale qualitative survey involving in-depth interviews of winery managers and industry leaders. Findings The findings indicated that key strategies in the domestic sector included a focus on cellar door sales combined with establishing links with the tourism industry, together with an incremental expansion of domestic markets. For the international sector, additional strategies included targeting familiar, psychically-close and niche markets in the initial stages of exporting, as well as taking advantage of firm-specific strengths and managerial competencies. Originality/value Not previously regarded as a major wine producing region of Australia, the Queensland wine industry has received limited attention in the literature, particularly the reasons for its rapid growth in recent years. The article helps to identify the strategies used by wineries in growing the industry.

Promoting Staywild: An examination of promotional strategies for a niche online

This paper will provide an overview of a joint research initiative by the Queensland University of Technology in conjunction with the Australian Smart Services Cooperative Research Centre into the development and analysis of online communities (OLCs). This project aimed to create an exciting and innovative web space (Staywild.com.au) around the concept of adventure travel. This paper considers the literature on promoting and building online communities. It also discusses methods for promotion and encouraging participation. These methods emerged from the literature and the results of a Staywild user survey. In our research for this paper we found little work that focused on promoting and building OLCs for non-profit organisations. This paper thus contributes to the field in its work towards developing a standardised method of marketing and promotion that can be applied to niche non-profit communities.

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

Can we teach advertising students to think? Strategies to engage student thinking

Understanding and effectively managing students’ engagement in education plays a significant role in enhancing learning processes and outcomes. Research has shown that students learn more when they are actively engaged in their learning. However, as many educators know, this is not as easy as one might expect. Using a range of teaching approaches, we attempt to impart knowledge and develop understanding and comprehension (Angelo 1993; Biggs and Telfer 1987; Patti 2003; Ranburuth and McCormick 2001). These vary from “information dump” or teacher-centric approaches, to those that stimulate more active involvement. From the literature, we know that experiential learning, such as those strategies that help students acquire practice skills, apply critical thought and active learning, are likely to have achieve higher levels of intellectual skill and ability (Benson and Blackman 2003; Hampton and Lawrence 1995; Hopkinson and Hogg 2004; Kolb 1984).

The role of alternative message strategies in advertising performance : challenges to the B2B marketing paradigm

In this study the impact of message strategy on advertising performance will be in examined in a business-to-business (B2B) context. From a theoretical standpoint, the study will explore differences in message type between symbolic and literal approaches in B2B advertisements. While there has been much discussion on the effect of symbolism, (eg. metaphors, abstract images and figurative language), an empirically-tested scale that measures the degree of symbolism has not been developed. This research project focuses on development of a methodological scale to accurately test the difference in the direction of message appeals. Thus, insights in the role of message strategy in the B2B adoption process are anticipated with contributions in future consumer and business advertising research.