Epithelial-mesenchymal transition and mesenchymal-epithelial transition are essential for the acquisition of stem cell properties in hTERT-immortalised oral epithelial cells

BACKGROUND INFORMATION: Evidence has shown that mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are linked to stem cell properties. We currently lack a model showing how the occurrence of MET and EMT in immortalised cells influences the maintenance of stem cell properties. Thus, we established a project aiming to investigate the roles of EMT and MET in the acquisition of stem cell properties in immortalised oral epithelial cells. RESULTS: In this study, a retroviral transfection vector (pLXSN-hTERT) was used to immortalise oral epithelial cells by insertion of the hTERT gene (hTERT(+)-oral mucosal epithelial cell line [OME]). The protein and RNA expression of EMT transcriptional factors (Snail, Slug and Twist), their downstream markers (E-cadherin and N-cadherin) and embryonic stem cell markers (OCT4, Nanog and Sox2) were studied by reverse transcription PCR and Western blots in these cells. Some EMT markers were detected at both mRNA and protein levels. Adipocytes and bone cells were noted in the multi-differentiation assay, showing that the immortal cells underwent EMT. The differentiation assay for hTERT(+)-OME cells revealed the recovery of epithelial phenotypes, implicating the presence of MET. The stem cell properties were confirmed by the detection of appropriate markers. Altered expression of alpha-tubulin and gamma-tubulin in both two-dimensional-cultured (without serum) and three-dimensional-cultured hTERT(+)-OME spheroids indicated the re-programming of cytoskeleton proteins which is attributed to MET processes in hTERT(+)-OME cells. CONCLUSIONS: EMT and MET are essential for hTERT-immortalised cells to maintain their epithelial stem cell properties.

Building a community of learners within the STEM higher education classroom

Building rich and authentic learning experiences in the STEM classroom, is a challenge for many educators within Higher Education. While many Higher Education Institutions have embraced the need to transform current teaching and learning practices and include a range of online tools, this has often been met with some resistance and approaches that do not always recognise the academic who are a critical component to the success of the transformational process. Over the last decade the Internet has evolved from being a tool used by a few dedicated educators to one that is being used by the majority of educators. However, what is important is how this great resource is used in teaching and learning to allow students to build knowledge. The ability for students to construct knowledge and engage in higher order thinking skills is at the heart of educational practices, and building a community of learners has the potential to support these practices, especially within STEM education. This paper explores the relationship between students and an academic teaching in a technology rich STEM learning environment and their adoption of social community and shared tools. In particular the paper reports on the critical components that make a successful community of learners and the educational tools and approaches that were successfully used to enhance the student learning experience in a STEM classroom.

Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer

Castration is the standard therapy for advanced prostate cancer (PC). Although this treatment is initially effective, tumors invariably relapse as incurable, castration-resistant PC (CRPC). Adaptation of androgen-dependent PC cells to an androgen-depleted environment or selection of pre-existing,CRPC cells have been proposed as mechanisms of CRPC development. Stem cell (SC)-like PC cells have been implicated not only as tumor initiating/maintaining in PC but also as tumor-reinitiating cells in CRPC. Recently, castration-resistant cells expressing the NK3 homeobox 1 (Nkx3-1) (CARNs), the other luminal markers cytokeratin 18 (CK18) and androgen receptor (AR), and possessing SC properties, have been found in castrated mouse prostate and proposed as the cell-of-origin of CRPC. However, the human counterpart of CARNs has not been identified yet. Here, we demonstrate that in the human PC xenograft BM18, preexisting SC-like and neuroendocrine (NE) PC cells are selected by castration and survive as totally quiescent. SClike BM18 cells, displaying the SC markers aldehyde dehydrogenase 1A1 or NANOG, coexpress the luminal markers NKX3-1, CK18, and a low level of AR (ARlow) but not basal or NE markers. These CR luminal SC-like cells, but not NE cells, reinitiate BM18 tumor growth after androgen replacement. The ARlow seems to mediate directly both castration survival and tumor reinitiation. This study identifies for the first time in human PC SC-/CARN-like cells that may represent the cell-of-origin of tumor reinitiation as CRPC. This finding will be fundamental for refining the hierarchy among human PC cancer cells and may have important clinical implications.

The current state of play in human neural stem cell models : what we have learnt from the rodent

Rodent (mouse and rat) models have been crucial in developing our understanding of human neurogenesis and neural stem cell (NSC) biology. The study of neurogenesis in rodents has allowed us to begin to understand adult human neurogenesis and in particular, protocols established for isolation and in vitro propagation of rodent NSCs have successfully been applied to the expansion of human NSCs. Furthermore, rodent models have played a central role in studying NSC function in vivo and in the development of NSC transplantation strategies for cell therapy applications. Rodents and humans share many similarities in the process of neurogenesis and NSC biology however distinct species differences are important considerations for the development of more efficient human NSC therapeutic applications. Here we review the important contributions rodent studies have had to our understanding of human neurogenesis and to the development of in vitro and in vivo NSC research. Species differences will be discussed to identify key areas in need of further development for human NSC therapy applications.

Linking pedagogical knowledge practices and student outcomes in STEM education for primary schools

STEM education is a new frontier in Australia, particularly for primary schools. However, the E in STEM needs to have a stronger focus with science and mathematics concepts aligned to the presiding curricula. In addition, pedagogical knowledge practices such as planning, preparation, teaching strategies, assessment and so forth need to be connected to key concepts for developing a STEM education. One of the aims of this study was to understand how a pedagogical knowledge practice framework could be linked to student outcomes in STEM education. Specifically, this qualitative research investigated Year 4 students’ involvement in an integrated STEM education program that focused on science concepts (e.g., states of matter, testing properties of materials) and mathematics concepts (such as 3D shapes and metric measurements: millilitres, temperature, grams, centimetres) for designing, making and testing a strong and safe medical kit to insulate medicines at desirable temperatures. Eleven pedagogical knowledge practices (e.g., planning, preparation, teaching strategies, classroom management, and assessment) were used as a framework for understanding how teaching may be linked to student outcomes in STEM education. For instance, “planning” involved devising a student booklet as a resource for students to understand the tasks required of them, which also provided space for them to record ideas, results and information. Planning involved linking national and state curriculum documents to the STEM education activities. More studies are required around pedagogical knowledge frameworks to understand what students learn when involved in STEM education, particularly with the inclusion of engineering education.

Digital literacies: Understanding the literate practices of refugee kids in an Afterschool Media Club

Since the 2000s, teachers in an increasing number of Australian schools have been learning how to support students with refugee backgrounds. For some of these students, entry into the Australian school system is not easy. English literacy is integral to some of the challenges confronting the students. In response, educators have been developing and researching ways of engaging with the students’ language and literacy learning. Much of the focus has been on traditional print-based school literacies. In contrast, I look here at student engagement in digital literacies in an after-school media club. Several concepts from the theory of French sociologist, Pierre Bourdieu are useful for understanding the position of students of refugee background in the Australian school system. Like other conflict theories, Bourdieusian theory has sometimes been criticised as ‘pessimistic’, that is, for suggesting that schools necessarily reproduce social disadvantage. However, others have used Bourdieusian theory to analyse and critique the reproductive work of schooling for groups of students who experience educational disadvantage. I align myself with this latter tradition. Specifically, I use Bourdieu’s triad of concepts to explain aspects of the literacy education experiences of some young people of refugee background: field, capital and habitus. In particular, I look at questions of the legitimation of students’ competences as capital in literate fields within and beyond the school context. Data are drawn from an Australian Research Council-funded project, Digital Learning and Print Literacy: A design experiment for the reform of low socio-economic, culturally diverse schools (2009-14). The data analysed in this chapter include interviews and observations relating to the participation of two Congolese girls in an after school media club. Implications are drawn for teachers of literacy in culturally and linguistically diverse contexts. Consideration is made of early childhood, primary and secondary settings.

Model-based analysis and optimization of bioreactor for hematopoietic stem cell cultivation

One of the problems to be solved in attaining the full potentials of hematopoietic stem cell (HSC) applications is the limited availability of the cells. Growing HSCs in a bioreactor offers an alternative solution to this problem. Besides, it also offers the advantages of eliminating labour intensive process as well as the possible contamination involved in the periodic nutrient replenishments in the traditional T-flask stem cell cultivation. In spite of this, the optimization of HSC cultivation in a bioreactor has been barely explored. This manuscript discusses the development of a mathematical model to describe the dynamics in nutrient distribution and cell concentration of an ex vivo HSC cultivation in a microchannel perfusion bioreactor. The model was further used to optimize the cultivation by proposing three alternative feeding strategies in order to prevent the occurrence of nutrient limitation in the bioreactor. The evaluation of these strategies, the periodic step change increase in the inlet oxygen concentration, the periodic step change increase in the media inflow, and the feedback control of media inflow, shows that these strategies can successfully improve the cell yield of the bioreactor. In general, the developed model is useful for the design and optimization of bioreactor operation.

Science, Technology, Engineering, and Maths (STEM)

"Historically, science had a place in education before the time of Plato and Aristotle (e.g., Stonehenge). Technology gradually increased since early human inventions (e.g., indigenous tools and weapons), rose up dramatically through the industrial revolution and escalated exponentially during the twentieth and twenty-first centuries, particularly with the advent of the Internet. Engineering accomplishments were evident in the constructs of early civil works, including roads and structural feats such as the Egyptian pyramids. Mathematics was not as clearly defined BC (Seeds 2010), but was utilized for more than two millennia (e.g., Archimedes, Kepler, and Newton) and paved its way into education as an essential scientific tool and a way of discovering new possibilities. Hence, combining science, technology, engineering, and mathematics (STEM) areas should not come as a surprise but rather as a unique way of packaging what has been ..."--Publisher Website

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplant determines the kinetics of acute Graft-Versus-Host Disease

Background Preparative myeloablative conditioning regimens for allogeneic hematopoietic stem-cell transplantation (HSCT) may control malignancy and facilitate engraftment but also contribute to transplant related mortality, cytokine release, and acute graft-versus-host disease (GVHD). Reduced intensity conditioning (RIC) regimens have decreased transplant related mortality but the incidence of acute GVHD, while delayed, remains unchanged. There are currently no in vivo allogeneic models of RIC HSCT, limiting studies into the mechanism behind RIC-associated GVHD. Methods We developed two RIC HSCT models that result in delayed onset GVHD (major histocompatibility complex mismatched (UBI-GFP/BL6 [H-2b]→BALB/c [H-2d]) and major histocompatibility complex matched, minor histocompatibility mismatched (UBI-GFP/BL6 [H-2b]→BALB.B [H-2b])) enabling the effect of RIC on chimerism, dendritic cell (DC) chimerism, and GVHD to be investigated. Results In contrast with myeloablative conditioning, we observed that RIC-associated delayed-onset GVHD is characterized by low production of tumor necrosis factor-α, maintenance of host DC, phenotypic DC activation, increased T-regulatory cell numbers, and a delayed emergence of activated donor DC. Furthermore, changes to the peritransplant milieu in the recipient after RIC lead to the altered activation of DC and the induction of T-regulatory responses. Reduced intensity conditioning recipients suffer less early damage to GVHD target organs. However, as donor cells engraft, activated donor DC and rising levels of tumor necrosis factor-α are associated with a later onset of severe GVHD. Conclusions Delineating the mechanisms underlying delayed onset GVHD in RIC HSCT recipients is vital to improve the prediction of disease onset and allow more targeted interventions for acute GVHD.

Analysis of moderation practices in a large STEM-focused faculty

Moderation of assessment constitutes a crucial element of the learning and teaching process at the university. Yet, despite its importance, many academics have confusing beliefs and attitudes towards moderation practices, processes and procedures. This paper reports on a qualitative study conducted in a Science, Technology, Engineering and Mathematics (STEM)-focused faculty at a large Australian higher education institution. The findings of the study revealed a strong need for further investigation on the ways moderation is understood and enacted by academics within a STEM-specific context and informed redevelopment of the faculty’s internal moderation policy.

Mesenchymal stem cells as mediators of the neuronal cell niche

This study examined the role of heparan sulfate proteoglycans (HSPGs) in neural lineage differentiation of human mesenchymal stem cells (hMSCs). Several HSPGs were identified as potential new targets controlling neural fate specification and may be applied to the development of improved models to examine and repair brain damage. hMSCs were characterised throughout extended in vitro expansion for neural lineage potential (neurons, astrocytes, oligodendrocytes) and differentiated using terminal differentiation and intermediate sphere formation. Brain damage and neurological disorders caused by injury or disease affect a large number of people often resulting in lifelong disabilities. Multipotent mesenchymal stem cells have a large capacity for self-renewal and provide an excellent model to examine the regulation and contribution of both stem cells and their surrounding microenvironment to the repair of neural tissue damage.

Engaging students (and their teachers) in STEM through robotics

Robotics@QUT is a university outreach program aimed at building pre- and in-service teacher capacity to encourage interest in Science, Technology, Engineering and Mathematics (STEM) subjects with school children from low socio-economic status areas. Currently over 35 schools are involved in the outreach program. Professional Development workshops are provided to teachers to build their knowledge in implementing robotics-based STEM activities in their classrooms, robotics loan kits are provided, and pre-service teacher visits arranged to provide the teachers with on-going support. The program also provides opportunities for school students to engage in robotics-based on-campus activities and competitions and is seen as a way to build aspirations for university. This paper presents an interim evaluation that examines the value of the Robotics@QUT program for the teachers, pre-service teachers and school students participating in the program. Surveys were administered to determine the participants’ perceived benefits of being involved and their perceptions of the program. The data gathered from the teachers showed that they had gained knowledge and confidence and felt that the Robotics@QUT program had assisted them to deliver engaging robotics-based STEM activities in their classrooms. The pre-service teachers’ responses focused on benefits for themselves, for their future teaching careers and for the school students involved. The school students’ responses focused on their increased knowledge and confidence to pursue future STEM studies and careers.