The stimulation of healing within a rat calvarial defect by mPCL–TCP/collagen scaffolds loaded with rhBMP-2

Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly 3-caprolactone/tricalcium phosphate (mPCL–TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL–TCP/collagen scaffolds with 5 mg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing microcomputed tomography (mCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL–TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non- BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by mCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, microcompression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL–TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect < mPCL–TCP/collagen < mPCL–TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL–TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects. Crown Copyright 2008 Published by Elsevier Ltd. All rights reserved.

P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions.

It is known that adenosine 5'-triphosphate (ATP) is a cotransmitter in the heart. Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X(1-7) and P2Y(1-14) receptors; however, the presence of P2X and P2Y receptor subtypes in strategic cardiac locations such as the sinoatrial node has not been determined. An understanding of P2X and P2Y receptor localization would facilitate investigation of purine receptor function in the heart. Therefore, we used quantitative PCR and in situ hybridization to measure the expression of mRNA of all known purine receptors in rat left ventricle, right atrium and sinoatrial node (SAN), and human right atrium and SAN. Expression of mRNA for all the cloned P2 receptors was observed in the ventricles, atria, and SAN of the rat. However, their abundance varied in different regions of the heart. P2X(5) was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y(1), P2Y(2), and P2Y(14) mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y(2) and P2Y(14) levels were highest, respectively. We extended these studies to investigate P2X(4) receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X(4) receptor mRNA was upregulated by 93% in SAN (P < 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X(4)-mediated effects might be modulated in heart failure. mRNA for P2X(4-7) and P2Y(1,2,4,6,12-14), but not P2X(2,3) and P2Y(11), was detected in human right atrium and SAN. In addition, mRNA for P2X(1) was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X(4) and P2X(7) mRNA was the highest for P2X receptors. P2Y(1) and P2Y(2) mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y(1), P2Y(2), and P2Y(14) were the most abundant P2Y receptor subtypes in human SAN. This study shows a widespread distribution of P2 receptor mRNA in rat heart tissues but a more restricted presence and distribution of P2 receptor mRNA in human atrium and SAN. This study provides further direction for the elucidation of P2 receptor modulation of heart rate and contractility.

Utilisation of seed resources by small mammals : a two-way interaction

Within the Australian wet tropics bioregion, only 900 000 hectares of once continuous rainforest habitat between Townsville and Cooktown now remains. While on the Atherton Tableland, only 4% of the rainforest that once occurred there remains today with remnant vegetation now forming a matrix of rainforest dispersed within agricultural land (sugarcane, banana, orchard crops, townships and pastoral land). Some biologists have suggested that remnants often support both faunal and floral communities that differ significantly from remaining continuous forest. Australian tropical forests possess a relatively high diversity of native small mammal species particularly rodents, which unlike larger mammalian and avian frugivores elsewhere, have been shown to be resilient to the effects of fragmentation, patch isolation and reduction in patch size. While small mammals often become the dominant mammalian frugivores, in terms of their relative abundance, the relationship that exists between habitat diversity and structure, and the impacts of small mammal foraging within fragmented habitat patches in Australia, is still poorly understood. The relationship between foraging behaviour and demography of two small mammal species, Rattus fuscipes and Melomys cervinipes, and food resources in fragmented rainforest sites, were investigated in the current study. Population densities of both species were strongly related with overall density of seed resources in all rainforest fragments. The distribution of both mammal species however, was found to be independent of the distribution of seed resources. Seed utilisation trials indicated that M.cervinipes and R.fuscipes had less impact on seed resources (extent of seed harvesting) than did other rainforest frugivores. Experimental feeding trials demonstrated that in 85% of fruit species tested, rodent feeding increased seed germination by a factor of 3.5 suggesting that in Australian tropical rainforest remnants, small mammals may play a significant role in enhancing germination of large seeded fruits. This study has emphasised the role of small mammals in tropical rainforest systems in north eastern Australia, in particular, the role that they play within isolated forest fragments where larger frugivorous species may be absent.

'Black is beautiful', and Indigenous : Aboriginal authorship in Australian popular music

The ‘black is beautiful’ movement began in the United States in the early sixties, and changed mainstream attitudes towards the body, fashion and personal aesthetics, gaining African American people a new sense of pride in being – and being called – ‘black’. In Australia the movement also had implications for changing the political meanings of ‘black’ in white society. However, it is not until the last decade, through the global influence of Afro-American music, that a distinctly Indigenous sense of black sexiness has captured the attention of mainstream audiences. The article examines such recent developments, and suggests that, through the appropriation of Afro-American aesthetics and styles, Indigenous producers and performers have developed new forms of Indigenous public agency, demonstrating that black is beautiful, and Indigenous.

Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells

The growth and differentiation of mesenchymal stem cells is controlled by various growth factors, the activities of which can be modulated by heparan sulfates. We have previously underscored the necessity of sulfated glycosaminoglycans for the FGF-2-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of heparan sulfate to cultures of primary rat MSCs stimulates their proliferation leading to increased expression of osteogenic markers and enhanced bone nodule formation. FGF-2 can also increase the proliferation and osteogenic differentiation of rMSCs when applied exogenously during their linear growth. However, as opposed to exogenous HS, the continuous use of FGF-2 during in vitro differentiation completely blocked rMSC mineralization. Furthermore, we show that the effects of both FGF-2 and HS are mediated through FGF receptor 1 (FGFR1) and that inhibition of signaling through this receptor arrests cell growth resulting in the cells being unable to reach the critical density necessary to induce differentiation. Interestingly, blocking FGFR1 signaling in post-confluent osteogenic cultures significantly increased calcium deposition. Taken together our data clearly suggests that FGFR1 signaling plays an important role during osteogenic differentiation, firstly by stimulating cell growth that is closely followed by an inhibitory affect once the cells have reached confluence. It also underlines the importance of HS as a co-receptor for the signaling of endogenous FGF-2 and suggests that purified glycosaminoglycans may be attractive alternatives to growth factors for improved ex vivo growth and differentiation of MSCs.

Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 lg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (lCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factorbased therapies.

RatSLAM on the edge : revealing a coherent representation from an overloaded rat brain

The RatSLAM system can perform vision based SLAM using a computational model of the rodent hippocampus. When the number of pose cells used to represent space in RatSLAM is reduced, artifacts are introduced that hinder its use for goal directed navigation. This paper describes a new component for the RatSLAM system called an experience map, which provides a coherent representation for goal directed navigation. Results are presented for two sets of real world experiments, including comparison with the original goal memory system's performance in the same environment. Preliminary results are also presented demonstrating the ability of the experience map to adapt to simple short term changes in the environment.

Cherbourg time : young black and deadly art 2003-2007

Art is most often at the margins of community life, seen as a distraction or entertainment only; an individual’s whim. It is generally seen as without a useful role to play in that community. This is a perception of grown-ups; children seem readily to accept an engagement with art making. Our research has shown that when an individual is drawn into a crafted art project where they have an actual involvement with the direction and production of the art work, then they become deeply engaged on multiple levels. This is true of all age groups. Artists skilled in community collaboration are able to produce art of value that transcends the usual judgements of worth. It gives people a licence to unfetter their imagination and then cooperatively be drawn back to a reachable visual solution. If you engage with children in a community, you engage the extended family at some point. The primary methodology was to produce a series of educationally valid projects at the Cherbourg State School that had a resonance into that community, then revisit and refine them where necessary and develop a new series that extended all of the positive aspects of them. This was done over a period of five years. The art made during this time is excellent. The children know it, as do their families, staff at the school, members of the local community and the others who have viewed it in exhibitions in far places like Brisbane and Melbourne. This art and the way it has been made has been acknowledged as useful by the children, teachers and the community, in educational and social terms. The school is a better place to be. This has been acknowledged by the children, teachers and the community The art making of the last five years has become an integral part of the way the school now operates and the influence of that has begun to seep into other parts of the community. Art needs to be taken from the margins and put to work at the centre.

Investigating international accounting standard setting : the black box of IFRS 6

This paper examines the role of powerful entities and coalitions in shaping international accounting standards. Specifically, the focus is on the process by which the International Accounting Standards Board (IASB) developed IFRS 6, Exploration for and Evaluation of Mineral Resources. In its Issues Paper, the IASB recommended that the successful efforts method be mandated for pre-production costs, eliminating the choice previously available between full cost and successful efforts methods. In spite of the endorsement of this view by a majority of the constituents who responded to the Issues Paper, the final outcome changed nothing, with choice being retained. A compelling explanation of this disparity between the visible inputs and outputs of the standard setting process is the existence of a “black box”, in which powerful extractive industries entities and coalitions covertly influenced the IASB to secure their own ends and ensure that the status quo was maintained