Adult skeletal muscle stem cell migration is mediated by a blebbing/amoeboid mechanism

Adult skeletal muscle possesses a resident stem cell population called satellite cells which are responsible for tissue repair following damage. Satellite cell migration is crucial in promoting rapid tissue regeneration but is a poorly understood process. Furthermore, the mechanisms facilitating satellite cell movement have yet to be elucidated. Here the process of satellite cell migration has been investigated revealing that they undergo two distinct phases of movement; firstly under the basal lamina and then rapidly increasing their velocity when on the myofibre surface. Most significantly we show that satellite cells move using a highly dynamic blebbing based mechanism and not via lamellopodia mediated propulsion. We show that nitric oxide and non-canonical Wnt signalling pathways are necessary for regulating the formation of blebs and the migration of satellite cells. In summary, we propose that the formation of blebs and their necessity for satellite cell migration has significant implications in the future development of therapeutic regimes aimed at promoting skeletal muscle regeneration

Community development and enterprise culture : prospects and dilemmas

Community Development as a form of practice promotes empowerment and social justice. Its origins lie in people\u27s collective struggle to be heard, recognised and accorded full citizenship in society. It has developed strategies to achieve social change that challenge dominant ways of thinking, policy and resource allocation in society. \u27Enterprise culture has its origins in the individualism and competitiveness of capitalism. These essentially neo-liberalist concepts have been remoulded into a radical political program of change sponsored by the state under the guise of new managerialism, competitive tendering and privatization. This research seeks to examine the interface between community development and enterprise culture as a potential site of tension and contestation through an analysis of discourse. The initial task, therefore, was to elaborate the concept of enterprise culture and examine the ways enterprise culture has been manifested in community development. The focus has been on practitioners committed to community development through a qualitative, empirical approach with a view to discerning their views on the relevance and impact of enterprise culture on their work. Community development provides a useful domain for interrogating the infiltration of the concept of the enterprise culture because of its history of opposition and mobilisation. The research seeks to understand the ways in which the forms of enterprise culture as an essentially cultural project are manifested in practice contexts and to analyse the nature of the response to its various manifestations. As a result, it constitutes more than just a critique of any one of these forms, eg, privatisation, tendering out, managerialism, and instead seeks to investigate the degree to which a cultural shift may be occurring towards notions of greater individualism and away from collective notions of responsibility, obligation and citizenship. The research critically analyses the impact of enterprise culture on Australian social policy through the case study of community development practice. The manifestations of enterprise culture are investigated at various levels, with an emphasis on the responses of practitioners. A related aim is to reveal the range of possible responses to the infiltration of the enterprise culture in terms of values, language and practice into community development. Are new forms of practice emerging or is the field being steadily co-opted by government social and educational policy? Finally, the research should enable some future directions to be identified for the field of community development. The findings represent an initial attempt in an Australian context to establish the degree of influence that enterprise culture has had and/or will have on social policy. Chapter 1 examines the concept of enterprise culture and a background to its impact on community development as a domain of practice. The meaning of enterprise culture and its origins will be examined in Chapter 2. Its influence on Australian social policy is then discussed with particular reference to recent changes in Victoria regarding family services. In Chapter 3, the main features of critical discourse analysis are outlined as a framework for subsequent analysis of the links between discourse and hegemony. The work of Fairclough (1992, 1995) is utilised to highlight the relevance of discourse analysis to an examination of the infiltration of ideas associated with enterprise culture into the domain of community development. Chapter 4 provides an overview of the origins and defining characteristics of community development practice. The diverse beginnings and philosophical underpinnings are discussed and the main features of community development outlined in order to establish meanings attached to key concepts such as empowerment and participation. In Chapter 5, the findings of initial interviews with sixteen community development practitioners are discussed in terms of their perceptions of the impact of enterprise culture on their practice and the organisational culture within which they operate. These initial interviews were conducted in November-December 1996. A primary focus of the interviews was to establish the key words in their lexicon of practice and to provide an opportunity for reflection on the relative influence of discourse and practices associated with enterprise culture. A framework for analysing and making sense of the forms of response to enterprise culture is applied to the responses. Four forms of possible response are proposed and discussed in the context of the data. Follow up interviews were conducted in November-December 1997 and the findings of these interviews are discussed in Chapter 6. A particular emphasis in these interviews was on any changes in the lexicon of practice and indications of a change in the impact of discourse and practices associated with enterprise culture. The forms of response suggested in the framework outlined in Chapter 5 are discussed in the light of any movement in the responses of participants in the study. The implications of the findings are discussed in the context of the framework of responses or forms of embrace of enterprise culture analysed in earlier chapters. Finally, in Chapter 7, the potential for community development as a form of practice to transcend or at least accommodate the impact of enterprise culture through strategic forms of embrace is discussed and possible strategies based on the research that may assist in the development of this response are proposed

Ab-Initio Studies into Intrinsic Piezoelectric Properties

We formulate a method of understanding the intrinsic piezoelectric properties of a perovskite system on an atomistic level using a density functional theory (DFT) methodology implemented into the electron density code CASTEP. First we consider the basic unary perovskites; barium titanate, lead titanate and potassium niobate. Geometry optimisation, elastic compliance, linear response, and simulated strain calculations are performed and the polarisation and piezoelectric coefficients are calculated. We then define the partial piezoelectric coefficient and demonstrate a way to generate the electron density shift, two novel methods in the understanding of intrinsic piezoelectric properties. We then study the binary piezoelectric lead titanate, performing the same calculations and analysing the electron density shift and partial piezoelectric coefficient in order to identify new features of binary systems, the equalisation between basic perovskite units and the "sawtooth" bonding asymmetry between the different B-site ions. Then the feasibility of these calculations is evaluated for bismuth ferrite, a material showing multiferroic properties. The conversion of non-orthonormal lattice axes to a cartesian coordinate system is addressed. We discuss the phonon and electric field calculations, and evaluate what is and is not possible. We find that structural and electron calculations are possible and report the optimised geometry, the elastic compliance, total electron density and spin maps, and the electron density shifts. We identify the symmetry, non-locality, and rotational modes in rhombohedral bismuth ferrite and suggest future research based on these properties

Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses

Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively