Fibroblast growth factor-2 over-rides insulin-like growth factor-I induced proliferation and cell survival in human neuroblastoma cells

The insulin-like growth factor (IGF) system is a key regulator of cell growth, survival and differentiation, and these functions are co-modulated by other growth factors including fibroblast growth factor-2 (FGF-2). To investigate IGF/FGF interactions in neuronal cells, we employed neuroblastoma cells (SK-N-MC). In serum free conditions proliferation of the SK-N-MC cells was promoted by IGF-I (25 ng/ml), but blunted by FGF-2 (50 ng/ml). IGF-I-induced proliferation was abolished in the presence of FGF-2 even when IGF-I was used at 100 ng/ml. In addition to our previously described FGF-2 induced proteolytic cleavage of IGFBP-2, we found that FGF-2 increased IGFBP-6 levels in conditioned medium (CM) without affecting IGFBP-6 mRNA abundance. Modulation of IGFBP-2 and -6 levels were not significant mechanisms involved in the blockade of IGF-I action since the potent IGF-I analogues [QAYL]IGF-I and des(1-3)IGF-I (minimal IGFBP affinity) were unable to overcome FGF-2 inhibition of cell proliferation. FGF-2 treated cells showed morphological differentiation expressing the TUJ1 neuronal marker while cells treated with IGF-I alone showed no morphological change. When IGF-I was combined with FGF-2, however, cell morphology was indistinguishable from that seen with FGF-2 alone. FGF-2 inhibited proliferation and enhanced differentiation was also associated with a 70% increase in cell death. Although IGF-I alone was potently anti-apoptotic (60% decreased), IGF-I was unable to prevent apoptosis when administrated in combination with FGF-2. Gene-array analysis confirmed FGF-2 activation of the intrinsic and extrinsic apoptotic pathways and blockade of IGF anti-apoptotic signaling. FGF-2, directly and indirectly, overcomes the proliferative and anti-apoptotic activity of IGF-I by complex mechanisms, including enhancement of differentiation and apoptotic pathways, and inhibition of IGF-I induced anti-apoptotic signalling. Modulation of IGF binding protein abundance by FGF-2 does not play a significant role in inhibition of IGF-I induced mitogenesis.

Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle

Diabetes is quickly reaching epidemic proportions, with 216 million people worldwide predicted to be diagnosed with the disease by 2010. While it appears that the expression of the insulin responsive glucose transporter isoform 4 (GLUT4) is not reduced in diabetic populations, overexpression of GLUT4 exclusively in muscle enhances insulin action and improves glucose homeostasis. Consequently, understanding the regulation of GLUT4 expression is considered important in identifying potential therapeutic targets for the treatment and management of insulin resistance and related disorders such as type 2 diabetes. Using transgenic mice, we have identified two conserved regions on the GLUT4 gene promoter that are required for normal skeletal muscle GLUT4 expression. The first region contains a binding site for the myocyte enhancer factor 2 (MEF2) transcription factor, between –464 and –473 bp, and it appears that a MEF2A/D heterodimer binds this sequence. However, this site is not sufficient to support full GLUT4 expression, and another region between –712 and –742 bp, termed Domain 1, is also required. A novel transcription factor, named the GLUT4 enhancer factor (GEF), was found to bind to this region. It appears that MEF2 and GEF physically interact in order to induce GLUT4 expression. A single bout of exercise is sufficient to increase both GLUT4 transcription and mRNA abundance. However, the molecular mechanisms underpinning this response remain largely unexplored, particularly in human skeletal muscle. Therefore, the aim of this study was to determine whether a single, acute bout of exercise increases the DNA-binding activity of both MEF2 and GEF in human skeletal muscle.

Effect of sex differences on human MEF2 regulation during endurance exercise

Women exhibit an enhanced capability for lipid metabolism during endurance exercise compared with men. The underlying regulatory mechanisms behind this sex-related difference are not well understood but may comprise signaling through a myocyte enhancer factor 2 (MEF2) regulatory pathway. The primary purpose of this study, therefore, was to investigate the protein signaling of MEF2 regulatory pathway components at rest and during 90 min of bicycling exercise at 60% VO2peak in healthy, moderately trained men (n = 8) and women (n = 9) to elucidate the potential role of these proteins in substrate utilization during exercise. A secondary purpose was to screen for mRNA expression of MEF2 isoforms and myogenic regulatory factor (MRF) family members of transcription factors at rest and during exercise. Muscle biopsies were obtained before and immediately after exercise. Nuclear AMP-activated protein kinase-{alpha} ({alpha}AMPK) Thr172 (P < 0.001), histone deacetylase 5 (HDAC5) Ser498 (P < 0.001), and MEF2 Thr (P < 0.01) phosphorylation increased with exercise. No significant sex differences were observed at rest or during exercise. At rest, no significant sex differences were observed in mRNA expression of the measured transcription factors. mRNA for transcription factors MyoD, myogenin, MRF4, MEF2A, MEF2C, MEF2D, and peroxisome proliferator-activated receptor-{gamma} coactivator 1{alpha} (PGC1{alpha}) were significantly upregulated by exercise. Of these, MEF2A mRNA increased 25% specifically in women (P < 0.05), whereas MEF2D mRNA tended to increase in men (P = 0.11). Although minor sex differences in mRNA expression were observed, the main finding of the present study was the implication of a joint signaling action of AMPK, HDAC5, and PGC1{alpha} on MEF2 in the immediate regulatory response to endurance exercise. This signaling response was independent of sex.

Non-retinal light stimulation and the human biological clock

Since 1998, debate has occurred over whether light synchronises the human biological clock through the visual system only, or if the light penetrating our skin is also influential. This thesis provides definitive, debate ending, evidence that skin exposure to even intensely bright light has no impact on circadian timing. The portfolio presents a review of the literature regarding the efficacy of dialectical behavior therapy as a treatment for borderline personality disorder, a summary of the proposed mechanisms of action on the various treatment components, and a description of the clinical application of the four 'skills training modules' via the use of four case study examples.

Nursing and justice as a basic human need

This paper explores the idea that justice is a basic human need akin to those famously depicted in Maslow’s hierarchy of human needs and, as such, warrants recognition as a core element in representative ideas about nursing. Early nurse theorists positioned the principles and practice of nursing as having their origins in ‘universal human needs’. The principle of deriving nursing care from human needs was thought to provide a guide not only for promoting health, but for preventing disease and illness. The nursing profession has had a longstanding commitment to social justice as a core professional value and ideal, obligating nurses to address the social conditions that undermine people’s health.The idea of justice as a universal human need per se and its possible relationship to people’s health outcomes has, however, not been considered. One reason for this is that justice in nursing discourse has more commonly been associated with law and ethics, and the legal and ethical responsibilities of nurses in relation to individualized patient care and, more recently, changing systems of care to improve health and health outcomes. Although this association is not incorrect, it is incomplete.A key aim of this paper is to redress this oversight and to encourage a broader conceptualization of justice as necessary for human survival, health and development, not merely as a professional value, or legal or ethical principle for guiding human conduct.

Enabling organisational cultural change using systemic strategic human resource management - a longitudinal study

The paper reports on a longitudinal assessment of sustained organizational cultural change in the Australian Taxation Office. Results from a major action research change project are provided. A clear finding from this research is that the cultural change had been sustained through the systemic application of strategic human resource management.

Voices in the human rights dialogue : the individual victim and the Australian Human Rights Commission

Framework for human rights protection in Australia - report of the National Human Rights Consultation Committee - the role of resolution of human rights complaints in the enforcement of human rights - use of alternative dispute resolution (ADR) - current role of the Australian Human Rights Commission (AHRC) - future role as an advocator and crusader for victims of human rights abuses - need for recognition and protection of the special status of the AHRC.

A neural network based human identification framework using ear images

This paper presents a framework that uses ear images for human identification. The framework makes use of Principal Component Analysis (PCA) for ear image feature extraction and Multilayer Feed Forward Neural Network for classification. Framework are proposed to improve recognition accuracy of human identification. The framework was tested on an ear image database to evaluate its reliability and recognition accuracy. The experimental results showed that our framework achieved higher stable recognition accuracy and over-performed other existing methods. The recognition accuracy stability and computation time with respect to different image sizes and factors were investigated thoroughly as well in the experiments.

The identification of mammalian species through the classification of hair patterns using image pattern recognition

The identification of mammals through the use of their hair is important in the fields of forensics and ecology. The application of computer pattern recognition techniques to this process provides a means of reducing the subjectivity found in the process, as manual techniques rely on the interpretation of a human expert rather than quantitative measures. The first application of image pattern recognition techniques to the classification of African mammalian species using hair patterns is presented. This application uses a 2D Gabor filter-bank and motivates the use of moments to classify hair scale patterns. Application of a 2D Gabor filter-bank to hair scale processing provides results of 52% accuracy when using a filter bank of size four and 72% accuracy when using a filter-bank of size eight. These initial results indicate that 2D Gabor filters produce information that may be successfully

Pedagogy of connections : findings of a collaborative action research project in outdoor and environmental education

Improving human-nature relationships is often a stated aim of outdoor education, yet this aim is not always made explicit in practice. This paper reflects on a pedagogical intervention which aims to find ways to explicitly develop students' connections with natural places through a tertiary outdoor and environmental education program. It describes the intervention process, which is guided by principles of collaborative action research. Furthermore, the intervention uses a multi-pronged teaching approach incorporating repeated visits to natural places utilizing different 'ways of knowing', weekly readings, journal writing, collaborative discussions, and others. We summarize the key findings of the research project and report that repeated visits to a natural place using different ways of knowing (e.g., historical, scientific, ecological, artistic, experiential, etc.) are influential in improving connections. We conclude with a discussion of the opportunities and dilemmas of using action research as a form of pedagogy.

Health promotion and climate change : exploring the core competencies required for action

Climate change poses serious threats to human health and well-being. It exacerbates existing health inequities, impacts on the social determinants of health and disproportionately affects vulnerable populations. In the Australian region these include remote Aboriginal communities, Pacific Island countries and people with low incomes. Given health promotion’s remit to protect and promote health, it should be well placed to respond to emerging climate-related health challenges. Yet, to date, there has been little evidence to demonstrate this. This paper draws on the findings of a qualitative study conducted in Victoria, Australia to highlight that; while there is clearly a role for health promotion in climate change mitigation and adaptation at the national and international levels, there is also a need for the engagement of health promoters at the community level. This raises several key issues for health promotion practice. To be better prepared to respond to climate change, health promotion practitioners first need to re-engage with the central tenets of the Ottawa Charter, namely the interconnectedness of humans and the natural environment and, secondly, the need to adopt ideas and frameworks from the sustainability field. The findings also open up a discussion for paradigmatic shifts in health promotion thinking and acting in the context of climate change.

Popular consent and foreign policy choices : war against the Philippines and covert action in Chile

It is usually assumed that US policymakers need to generate popular consent in order to undertake regime change against another state. This article explores the ways in which contextual factors such as the joint democracy effect, popular values and public moods influenced efforts by elites in the United States to generate popular consent for regime change in the Philippines and Chile. Against the backdrop of the Vietnam War, the United States undertook covert action in Chile due to public recognition of the target state's democratic credentials and a public mood opposed to further military ventures. In contrast, the absence of a strong joint democracy effect, a national mood infused with romantic nationalism qua militarism and social Darwinism facilitated efforts by US elites to generate consent for the invasion and occupation of the Philippines. Subsequently, this article contributes to understandings of the domestic-level factors that influence foreign policy decisions.

Automated classification of human daily activities in ambulatory environment

This paper presents a human daily activity classification approach based on the sensory data collected from a single tri-axial accelerometer worn on waist belt. The classification algorithm was realized to distinguish 6 different activities including standing, jumping, sitting-down, walking, running and falling through three major steps: wavelet transformation, Principle Component Analysis (PCA)-based dimensionality reduction and followed by implementing a radial basis function (RBF) kernel Support Vector Machine (SVM) classifier. Two trials were conducted to evaluate different aspects of the classification scheme. In the first trial, the classifier was trained and evaluated by using a dataset of 420 samples collected from seven subjects by using a k-fold cross-validation method. The parameters σ and c of the RBF kernel were optimized through automatic searching in terms of yielding the highest recognition accuracy and robustness. In the second trial, the generation capability of the classifier was also validated by using the dataset collected from six new subjects. The average classification rates of 95% and 93% are obtained in trials 1 and 2, respectively. The results in trial 2 show the system is also good at classifying activity signals of new subjects. It can be concluded that the collective effects of the usage of single accelerometer sensing, the setting of the accelerometer placement and efficient classifier would make this wearable sensing system more realistic and more comfortable to be implemented for long-term human activity monitoring and classification in ambulatory environment, therefore, more acceptable by users.

Activity recognition and abnormality detection with the switching hidden semi-Markov model

This paper addresses the problem of learning and recognizing human activities of daily living (ADL), which is an important research issue in building a pervasive and smart environment. In dealing with ADL, we argue that it is beneficial to exploit both the inherent hierarchical organization of the activities and their typical duration. To this end, we introduce the Switching Hidden Semi-Markov Model (S-HSMM), a two-layered extension of the hidden semi-Markov model (HSMM) for the modeling task. Activities are modeled in the S-HSMM in two ways: the bottom layer represents atomic activities and their duration using HSMMs; the top layer represents a sequence of high-level activities where each high-level activity is made of a sequence of atomic activities. We consider two methods for modeling duration: the classic explicit duration model using multinomial distribution, and the novel use of the discrete Coxian distribution. In addition, we propose an effective scheme to detect abnormality without the need for training on abnormal data. Experimental results show that the S-HSMM performs better than existing models including the flat HSMM and the hierarchical hidden Markov model in both classification and abnormality detection tasks, alleviating the need for presegmented training data. Furthermore, our discrete Coxian duration model yields better computation time and generalization error than the classic explicit duration model.