A crystallographic snapshot of tyrosine trans-phosphorylation in action

Tyrosine trans-phosphorylation is a key event in receptor tyrosine kinase signaling, yet, the structural basis for this process has eluded definition. Here, we present the crystal structure of the FGF receptor 2 kinases caught in the act of trans-phosphorylation of Y769, the major C-terminal phosphorylation site. The structure reveals that enzyme- and substrate-acting kinases engage each other through elaborate and specific interactions not only in the immediate vicinity of Y769 and the enzyme active site, but also in regions that are as much of 18 A away from D626, the catalytic base in the enzyme active site. These interactions lead to an unprecedented level of specificity and precision during the trans-phosphorylation on Y769. Time-resolved mass spectrometry analysis supports the observed mechanism of trans-phosphorylation. Our data provide a molecular framework for understanding the mechanism of action of Kallmann syndrome mutations and the order of trans-phosphorylation reactions in FGFRs. We propose that the salient mechanistic features of Y769 trans-phosphorylation are applicable to trans-phosphorylation of the equivalent major phosphorylation sites in many other RTKs.

Action inquiry into the use of standardized evaluation tools for music therapy : a real life journey within a parent-child community program

Sing & Grow is an early intervention music therapy project that provides community group music therapy programs to families with young children who encounter risk factors that may impact on parenting and optimal child develop variety of evaluation tools were devised and used over the first 3 years of the project. Upon the subsequent funding and expansion of the project at the end of this period, it was necessary to find, test and devise more rigorous, valid and reliable measures to withstand the scrutiny of researchers, and to combat the concerns and criticisms associated with the previous methods of data collection. An action inquiry project was therefore undertaken with two groups of project participants to trial the use of the Parenting Stress Index and Depression, Anxiety and Stress Scales, both recommended by leading psychologists. Key findings that will be discussed include the friction between the deficit-focussed nature of many psychometric tools and the strengths-based approach taken in service delivery, the level of difficulty in terms of literacy and comprehension for vulnerable respondents, and the lack of one tool with the ability to comprehensively measure all aspects of a broad scoping program. Keywords: music therapy, evaluation, PSI, DASS, action inquiry.

Having a yarn about smoking : using action research to develop a 'no smoking' policy within an Aboriginal health organisation

Objectives: This article reports on a culturally appropriate process of development of a smoke-free workplace policy within the peak Aboriginal Controlled Community Health Organisation in Victoria, Australia. Smoking is acknowledged as being responsible for at least 20% of all deaths in Aboriginal communities in Australia, and many Aboriginal health workers smoke. Methods: The smoke-free workplace policy was developed using the iterative, discursive and experience-based methodology of Participatory Action Research, combined with the culturally embedded concept of ‘having a yarn’. Results: Staff members initially identified smoking as a topic to be avoided within workplace discussions. This was due, in part, to grief (everyone had suffered a smoking related bereavement). Further, there was anxiety that discussing smoking would result in culturally difficult conflict. The use of yarning opened up a safe space for discussion and debate,enabling development of a policy that was accepted across the organisation. Conclusions: Within Aboriginal organisations, it is not sufficient to focus on the outcomes of policy development. Rather, due attention must be paid to the process employed in development of policy, particularly when that policy is directly related to an emotionally and communally weighted topic such as smoking.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

Parameter estimation for a phenomenological model of the cardiac action potential

The action potential (ap) of a cardiac cell is made up of a complex balance of ionic currents which flow across the cell membrane in response to electrical excitation of the cell. Biophysically detailed mathematical models of the ap have grown larger in terms of the variables and parameters required to model new findings in subcellular ionic mechanisms. The fitting of parameters to such models has seen a large degree of parameter and module re-use from earlier models. An alternative method for modelling electrically exciteable cardiac tissue is a phenomenological model, which reconstructs tissue level ap wave behaviour without subcellular details. A new parameter estimation technique to fit the morphology of the ap in a four variable phenomenological model is presented. An approximation of a nonlinear ordinary differential equation model is established that corresponds to the given phenomenological model of the cardiac ap. The parameter estimation problem is converted into a minimisation problem for the unknown parameters. A modified hybrid Nelder–Mead simplex search and particle swarm optimization is then used to solve the minimisation problem for the unknown parameters. The successful fitting of data generated from a well known biophysically detailed model is demonstrated. A successful fit to an experimental ap recording that contains both noise and experimental artefacts is also produced. The parameter estimation method’s ability to fit a complex morphology to a model with substantially more parameters than previously used is established.

Research in action for community informatics : A matter for conversation (editorial introduction)

This special issue of the Journal of Community Informatics brings together people from a diverse range of disciplines to discuss how academic researchers and community practitioners and activists can work together to explore the use of information and communication technologies, social media, augmented reality, and other forms of network technologies for research and action in pursuit of social responsibility. The aim is to connect people with ideas, ideas with research projects, and harness new media to further inquiry into socially just outcomes in our community. Some of the papers are based on presentations given at the "Research for Action: Networking University and Community for Social Responsibility" workshop chaired by Matthew Allen and Marcus Foth, at the Making Links 2010 conference in Perth, WA on 15 Nov 2010.

The theories of reasoned action and planned behaviour applied to business decision : a selective annotated bibliography

Purpose: This paper provides a selective annotated bibliography that summarises journal articles which have employed either the theory of reasoned action or the theory of planned behaviour to circumstances which are relevant to business activities. Design/methodology/approach: Searches were conducted on the EBSCO Host and ProQuest databases to identify papers that had used either the theory of reasoned action or theory of planned behaviour in their methodology. The bibliography was separated into three categories- financial decision making, strategic decision making, and professional decision making. Implications: The information presented in this paper is intended to assist and facilitate further research by broadening the awareness of the literature and providing examples of the application of the theory as it has been employed in prior research.

Using participatory action research in a community-based initiative addressing complex mental health needs

Objective: This paper describes the first phase of a larger project that utilizes participatory action research to examine complex mental health needs across an extensive group of stakeholders in the community. Method: Within an objective qualitative analysis of focus group discussions the social ecological model is utilized to explore how integrative activities can be informed, planned and implemented across multiple elements and levels of a system. Seventy-one primary care workers, managers, policy-makers, consumers and carers from across the southern metropolitan and Gippsland regions of Victoria, Australia took part in seven focus groups. All groups responded to an identical set of focusing questions. Results: Participants produced an explanatory model describing the service system, as it relates to people with complex needs, across the levels of social ecological analysis. Qualitative themes analysis identified four priority areas to be addressed in order to improve the system's capacity for working with complexity. These included: (i) system fragmentation; (ii) integrative case management practices; (iii) community attitudes; and (iv) money and resources. Conclusions: The emergent themes provide clues as to how complexity is constructed and interpreted across the system of involved agencies and interest groups. The implications these findings have for the development and evaluation of this community capacity-building project were examined from the perspective of constructing interventions that address both top-down and bottom-up processes.