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.

Striving for a better world: Lessons from Freire in Grenada, Jamaica and Australia

The author of this paper considers the influence of Paulo Freire’s pedagogical philosophy on educational practice in three different geographical/political settings. She begins with reflections on her experience as a facilitator at Freire’s seminar, held in Grenada in 1980 for teachers and community educators, on the integration of work and study. This case demonstrates how Freire’s method of dialogic education achieved outcomes for the group of thoughtful collaboration leading to conscientisation in terms of deep reflection on their lives as teachers in Grenada and strategies for decolonising education and society. The second case under consideration is the arts-based pedagogy shaping the work of the Area Youth Foundation (AYF) in Kingston, Jamaica. Young participants, many of them from tough socio-economic backgrounds, are empowered by learning how to articulate their own experiences and relate these to social change. They express this conscientisation by creating stage performances, murals, photo-novella booklets and other artistic products. The third case study describes and evaluates the Honey Ant Reader project in Alice Springs, Australia. Aboriginal children, as well as the adults in their community, learn to read in their local language as well as Australian Standard English, using booklets created from indigenous stories told by community Elders, featuring local customs and traditions. The author analyses how the “Freirean” pedagogy in all three cases exemplifies the process of encouraging the creation of knowledge for progressive social change, rather than teaching preconceived knowledge. This supports her discussion of the extent to which this is authentic to the spirit of the scholar/teacher Paulo Freire, who maintained that in our search for a better society, the world has to be made and remade. Her second, related aim is to raise questions about how education aligned with Freirean pedagogy can contribute to moving social change from the culture circle to the public sphere.

Challenges in embedding numeracy throughout the curriculum in three Queensland secondary schools

The new Australian Curriculum and national standardised testing have placed the teaching of numeracy across the curriculum at the forefront of what Australian schools must do. However, it has been left to schools to determine how they do this. Although there is a growing body of literature giving examples of pedagogies that embed numeracy in various learning areas, there are few studies of cross-curricular numeracy from the management perspective. This paper responds to the research question: How do selected Queensland secondary schools interpret and apply the Australian Curriculum requirement to embed numeracy throughout the curriculum? A multiple case study design was used to investigate the actions of the senior managers and mathematics teachers in three large secondary schools located in outer Brisbane. The numeracy practices in the three schools were interpreted from asocial constructivist perspective. The study found that in each school key managers had differing constructions of numeracy that led to confusion in administrative practices, policy development and leadership. The lack of coordinated cross-curricular action in numeracy in all three schools points to the difficulty that arises when teachers do not share the cross-curricular vision of numeracy present in the Australian Curriculum. The managers identified teachers’ commitment, understanding, or skills in relation to numeracy as significant barriers to the successful implementation of numeracy in their school. Adoption of the Australian Curriculum expectation of embedding numeracy across the curriculum will require school managers to explicitly commit to initiatives that require persistence,time and, most importantly, money.

The structures of the isomorphous potassium and rubidium salts of 4-nitrobenzoic acid and an overview of the metal complex stereochemistries of the alkali metal salt series with this ligand

The structures of the isomorphous potassium and rubidium polymeric coordination complexes with 4-nitrobenzoic acid, poly[mu2-aqua-aqua-mu3-(4-nitrobenzoato)-potassium], [K(C7H4N2O2)(H2O)2]n, (I) and poly[mu3-aqua-aqua-mu5-(4-nitrobenzoato)-rubidium], [Rb(C7H4N2O2)(H2O)2]n, (II) have been determined. In (I) the very distorted KO6 coordination sphere about the K+ centres in the repeat unit comprise two bridging nitro O-atom donors, a single bridging carboxyl O-atom donor and two water molecules, one of which is bridging. In the the Rb complex (II), the same basic MO6 coordination is found in the repeat unit but is expanded to RbO9 through a slight increase in the accepted Rb-O bond length range and includes an additional Rb-O(carboxyl) bond, completing a bidentate O,O'-chelate interaction, and additional bridging Rb-Onitro) and Rb-O(water) bonds. The comparative K-O and Rb-O bond length ranges are 2.738(3)-3.002(3)Ang. (I) and 2.884(2)-3.182(2)Ang. (II). The structure of (II) is also isomorphous as well as isostructural with the known structure of the nine-coordinate caesium 4-nitrobenzoate analogue, [Cs(C7H4N2O~2~)(H~2~O)2]n, (III) in which the Cs---O range is 3.047(4)-3.338(4)Ang. In all three complexes, common basic polymeric extensions are found, including two different centrosymmetric bridging interactions through both water and nitro groups as well as extensions along c through the p-related carboxyl group, giving a two-dimensional structure in (I). In (II) and (III), three-dimensional structures are generated through additional bridges through the nitro and water O-atoms. In all structures, both water molecules are involved in similar intra-polymer O-H...O hydrogen-bonding interactions to both carboxyl as well as water O-atom acceptors. A comparison of the varied coordination behaviour of the full set of Li-Cs salts with 4-nitrobenzoic acid is also made.

Structural optimization approach for specially shaped composite tank in spacecrafts

This study proposes an optimized approach of designing in which a model specially shaped composite tank for spacecrafts is built by applying finite element analysis. The composite layers are preliminarily designed by combining quasi-network design method with numerical simulation, which determines the ratio between the angle and the thickness of layers as the initial value of the optimized design. By adopting an adaptive simulated annealing algorithm, the angles and the numbers of layers at each angle are optimized to minimize the weight of structure. Based on this, the stacking sequence of composite layers is formulated according to the number of layers in the optimized structure by applying the enumeration method and combining the general design parameters. Numerical simulation is finally adopted to calculate the buckling limit of tanks in different designing methods. This study takes a composite tank with a cone-shaped cylinder body as example, in which ellipsoid head section and outer wall plate are selected as the object to validate this method. The result shows that the quasi-network design method can improve the design quality of composite material layer in tanks with complex preliminarily loading conditions. The adaptive simulated annealing algorithm can reduce the initial design weight by 30%, which effectively probes the global optimal solution and optimizes the weight of structure. It can be therefore proved that, this optimization method is capable of designing and optimizing specially shaped composite tanks with complex loading conditions.

Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway

Background There is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors. CSCs are thus considered the target for future cancer therapies. To achieve this goal, identifying potential therapeutic targets for CSCs is essential. Methods We used a natural product of vitamin E, gamma tocotrienol (gamma-T3), to treat mammospheres and spheres from colon and cervical cancers. Western blotting and real-time RT-PCR were employed to identify the gene and protein targets of gamma-T3 in mammospheres. Results We found that mammosphere growth was inhibited in a dose dependent manner, with total inhibition at high doses. Gamma-T3 also inhibited sphere growth in two other human epithelial cancers, colon and cervix. Our results suggested that both Src homology 2 domain-containing phosphatase 1 (SHP1) and 2 (SHP2) were affected by gamma-T3 which was accompanied by a decrease in K- and H-Ras gene expression and phosphorylated ERK protein levels in a dose dependent way. In contrast, expression of self-renewal genes TGF-beta and LIF, as well as ESR signal pathways were not affected by the treatment. These results suggest that gamma-T3 specifically targets SHP2 and the RAS/ERK signaling pathway. Conclusions SHP1 and SHP2 are potential therapeutic targets for breast CSCs and gamma-T3 is a promising natural drug for future breast cancer therapy.

Designing 'other' citizens into the city: Investigating perceptions of architectural opportunities for wildlife habitat in the Brisbane CBD

Traditional perceptions of the human-animal relationship in the urban context typically see the spatial rejection of wildlife from the built environment and limiting of biodiversity conservation programs to areas of natural reserve. As urban growth places further spatial demands on natural habitat and contributes to continued global biodiversity loss, the recently introduced conservation approach of reconciliation ecology makes a call promoting ecological stewardship through embedding wildlife habitat within human dominated areas. Coinciding with this, the architectural sphere has seen a recent trend of design investigation addressing artificial animal habitat as features of the built environment. Although these precedents are currently a niche and scattered trend they show potential to address the human-animal dualism challenging the framework of reconciliation ecology. This research explores the role design plays in influencing perceptions of urban wildlife habitat, particularly considering the need to create and communicate value around wildlife biodiversity as a component of urban cultural place-making and ecological literacy. The study purpose sets out to establish a set of approaches and cultural preferences with which to direct further classification and development of this architectural trend. Brisbane is utilised as a case study city, as a locale containing proximities of relatively high wildlife and human populations in an urban setting and an established legislative biodiversity heritage and ethic. Through use of a qualitative and quantitative questionnaire targeting Brisbane residents, the research methodology established that although respondents perceptions generally aligned with traditional prejudice against wildlife around human buildings, artificial habitat intervention would be supported within the CBD provided it allowed for adequate distancing of humans from wildlife and conformed with contextual surroundings, or otherwise addressed habitat through redevelopment at an urban scale. As such further research directions for artificial habitat should focus on integration of artificial habitat as a component of façade design or green infrastructure programs.

Information-theoretic analysis of brain white matter fiber orientation distribution functions

We propose a new information-theoretic metric, the symmetric Kullback-Leibler divergence (sKL-divergence), to measure the difference between two water diffusivity profiles in high angular resolution diffusion imaging (HARDI). Water diffusivity profiles are modeled as probability density functions on the unit sphere, and the sKL-divergence is computed from a spherical harmonic series, which greatly reduces computational complexity. Adjustment of the orientation of diffusivity functions is essential when the image is being warped, so we propose a fast algorithm to determine the principal direction of diffusivity functions using principal component analysis (PCA). We compare sKL-divergence with other inner-product based cost functions using synthetic samples and real HARDI data, and show that the sKL-divergence is highly sensitive in detecting small differences between two diffusivity profiles and therefore shows promise for applications in the nonlinear registration and multisubject statistical analysis of HARDI data.

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering

We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD)". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC) each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

A theoretical framework for designing and evaluating strategies to identify cases of serious child abuse and neglect

A central dimension of the State’s responsibility in a liberal democracy and any just society is the protection of individuals’ central rights and freedoms, and the creation of the minimum conditions under which each individual has an opportunity to lead a life of sufficient equality, dignity and value. A special subset of this responsibility is to protect those who are unable to protect themselves from genuine harm. Substantial numbers of children suffer serious physical, emotional and sexual abuse, and neglect at the hands of their parents and caregivers or by other known parties. Child abuse and neglect occurs in a situation of extreme power asymmetry. The physical, social, behavioural and economic costs to the individual, and the social and economic costs to communities, are vast. Children are not generally able to protect themselves from serious abuse and neglect. This enlivens both the State’s responsibility to protect the child, and the debate about how that responsibility can and should be discharged. A core question arises for all societies, given that most serious child maltreatment occurs in the family sphere, is unlikely to be disclosed, causes substantial harm to both individual and community, and infringes fundamental individual rights and freedoms. The question is: how can society identify these situations so that the maltreatment can be interrupted, the child’s needs for security and safety, and health and other rehabilitation can be met, and the family’s needs can be addressed to reduce the likelihood of recurrence? This chapter proposes a theoretical framework applicable for any society that is considering justifiable and effective policy approaches to identify and respond to cases of serious child abuse and neglect. The core of the theoretical framework is based on major principles from both classical liberal political philosophy (Locke and Mill), and leading political philosophers from the twentieth century and the first part of the new millennium (Rawls, Rorty, Okin, Nussbaum), and is further situated within fundamental frameworks of civil and criminal law, and health and economics.

A Bruch’s membrane substitute fabricated from silk fibroin supports the function of retinal pigment epithelial cells in vitro

Silk fibroin provides a promising biomaterial for ocular tissue reconstruction including the damaged outer blood-retinal barrier of patients afflicted with age-related macular degeneration (AMD). The aim of the present study was to evaluate the function of retinal pigment epithelial (RPE) cells in vitro, when grown on fibroin membranes manufactured to a similar thickness as Bruch’s membrane (3 μm). Confluent cultures of RPE cells (ARPE-19) were established on fibroin membranes and maintained under conditions designed to promote maturation over 4 months. Control cultures were grown on polyester cell culture well inserts (Transwell). Cultures established on either material developed a cobblestoned morphology with partial pigmentation within 12 weeks. Immunocytochemistry at 16 weeks revealed a similar distribution pattern between cultures for F-actin, ZO-1, ezrin, cytokeratin pair 8/18, RPE-65 and Na+/K+-ATPase. Electron microscopy revealed that cultures grown on fibroin displayed a rounder apical surface with a more dense distribution of microvilli. Both cultures avidly ingested fluorescent microspheres coated with vitronectin and bovine serum albumin (BSA), but not controls coated with BSA alone. VEGF and PEDF were detected in the conditioned medium collected from above and below both membrane types. Levels of PEDF were significantly higher than for VEGF on both membranes and a trend was observed towards larger amounts of PEDF in apical compartments. These findings demonstrate that RPE cell functions on fibroin membranes are equivalent to those observed for standard test materials (polyester membranes). As such, these studies support advancement to studies of RPE cell implantation on fibroin membranes in a preclinical model.

Prehospital paediatric burn care: New priorities in paramedic reporting

OBJECTIVE: The present study evaluates the prehospital care of paediatric burn patients in Queensland (QLD). As first aid (FA) treatment has been shown to affect burn progression and outcome, the FA treatment and the risk of associated hypothermia in paediatric patients were specifically examined in the context of paramedic management of burn patients. METHODS: Data were retrospectively collected from electronic ambulance response forms (eARFs) for paediatric burn patients (0-5 years) who were attended by Queensland Ambulance Service (QAS) from 2008 to 2010. Data were collected from 117 eARFs of incidents occurring within the Brisbane, Townsville and Cairns regions. RESULTS: Initial FA measures were recorded in 77.8% of cases, with cool running water FA administered in 56.4% of cases. The duration of FA was recorded in 29.9% of reports. The duration of FA was significantly shorter for patients in Northern QLD (median = 10 min, n = 10) compared with Brisbane (median = 15 min, n = 18), P = 0.005. Patient temperatures were recorded significantly more often in Brisbane than in other regions (P = 0.041); however, in total, only 24.8% of all patients had documented temperature readings. Of these, six (5%) were recorded as having temperatures ≤ 36.0°C. Burnaid(TM) was the most commonly used dressing and was applied to 55.6% of all patients; however, it was applied with a variety of different outer dressings. Brisbane paramedics applied Burnaid significantly less often (44.3%) compared with paramedics from Northern QLD (72.7%) and Far Northern QLD (60.9%), P = 0.025. CONCLUSIONS: Despite FA and patient temperatures being important prognostic factors for burn patients, paramedic documentation of these was often incomplete, and there was no consistent use of burns dressings.

Alteration of the C-terminal ligand specificity of the Erbin PDZ domain by allosteric mutational effects

Modulation of protein binding specificity is important for basic biology and for applied science. Here we explore how binding specificity is conveyed in PDZ (postsynaptic density protein-95/discs large/zonula occludens-1) domains, small interaction modules that recognize various proteins by binding to an extended C terminus. Our goal was to engineer variants of the Erbin PDZ domain with altered specificity for the most C-terminal position (position 0) where a Val is strongly preferred by the wild-type domain. We constructed a library of PDZ domains by randomizing residues in direct contact with position 0 and in a loop that is close to but does not contact position 0. We used phage display to select for PDZ variants that bind to 19 peptide ligands differing only at position 0. To verify that each obtained PDZ domain exhibited the correct binding specificity, we selected peptide ligands for each domain. Despite intensive efforts, we were only able to evolve Erbin PDZ domain variants with selectivity for the aliphatic C-terminal side chains Val, Ile and Leu. Interestingly, many PDZ domains with these three distinct specificities contained identical amino acids at positions that directly contact position 0 but differed in the loop that does not contact position 0. Computational modeling of the selected PDZ domains shows how slight conformational changes in the loop region propagate to the binding site and result in different binding specificities. Our results demonstrate that second-sphere residues could be crucial in determining protein binding specificity.

From users to citizens: Some thoughts on designing for polity and civics

This paper presents an essay aimed at prompting broad discussion crucial in keeping the interaction design discourse fresh, critical, and in motion. We trace the changing role of people who have advanced from consumers to producers, from stationary office workers to mobile urban nomads, from passive members of the plebs to active instigators of change. Yet, interaction designers often still refer to them only as ‘users.’ We follow some of the historic developments from the information superhighway to the smart city in order to provide the backdrop in front of which we critically analyse three core areas. First, the issue of echo chambers and filter bubbles in social media results in a political polarisation that jeopardises the formation of a functioning public sphere. Second, pretty lights and colourful façades in media architecture are increasingly making way for situated installations and interventions fostering community engagement. And third, civic activism is often reduced to forms of slacktivism. We synthesise our discussion to propose ‘citizen-ability’ as an alternative goal for interaction designers to aspire to in order to create new polities and civics for a better quality of life.

Widening participation creatively: Creative arts education for social inclusion

University participation among students from low socio-economic backgrounds in Australia is low and nationwide strategies are in place to help bridge the gap. This article presents a preliminary evaluation of a creative arts-based outreach program to raise awareness and aspiration for university study among students from low-income backgrounds. The program is part of a national Australian federally funded initiative, the Higher Education Participation and Partnerships Program. It reviews an outreach advertising program facilitated by a Brisbane university. We argue that arts education has a particular role in provoking attitudinal change, due to the self-reflective, meaning-making and expressive characteristics of arts-based disciplines. In evaluating the advertising program, the value of creativity and trust as techniques of student engagement is considered. Evaluation occurred in two outer suburban high schools in Brisbane (a State capital city), using surveys and ethnographic fieldwork. The findings support an engagement model that employs creativity and uses student facilitators (undergraduate and postgraduate) to deliver the program, to meet the program's aims.