Protumorigenic actions of S100A2 involve regulation of PI3/Akt signaling and functional interaction with Smad3

S100 family of calcium-binding proteins is commonly upregulated in a variety of tumor types and is often associated with tumor progression. Among several S100 members, altered expression of S100A2 is a potential diagnostic and prognostic marker in cancer. Several reports suggest a role for S100A2 in metastasis. Earlier, our studies established regulation of S100A2 by transforming growth factor- (TGF-) and its involvement in TGF--mediated cancer cell invasion and migration. However, the molecular mechanisms of S100A2 protumorigenic actions remain unexplored. In the present study, we demonstrate that overexpression of S100A2 in A549 lung cancer cells induced epithelialmesenchymal transition (EMT) followed by increased invasion, loose colony morphology in soft agar and enhanced Akt phosphorylation (Ser-473). Furthermore, overexpression of S100A2 led to increased tumor growth in immunocompromised mice. In agreement, immunohistochemical examination of resected xenograft tumors established inverse correlation between S100A2 and E-cadherin expression together with activated Akt signaling. Interestingly, our study demonstrates a strong dependence of S100A2 and Smad3 in TGF--induced Hep3B cell EMT and invasion. Most importantly, we demonstrate that these effects of S100A2 are manifested through functional interaction with Smad3, which is enhanced in the presence of high calcium and TGF-. S100A2 stabilizes Smad3 and binds to its C-terminal MH2 domain. Additionally, loss of S100A2 attenuates the transcription of TGF-/Smad3 target genes involved in tumor promotion, such as PA1-1 and vimentin. Collectively, our findings present the first mechanistic details of S100A2 protumorigenic actions and its involvement in TGF--mediated cancer cell invasion and EMT.

A Cause and Effect Analysis of Motion Trajectories for Modeling Actions

An action is typically composed of different parts of the object moving in particular sequences. The presence of different motions (represented as a 1D histogram) has been used in the traditional bag-of-words (BoW) approach for recognizing actions. However the interactions among the motions also form a crucial part of an action. Different object-parts have varying degrees of interactions with the other parts during an action cycle. It is these interactions we want to quantify in order to bring in additional information about the actions. In this paper we propose a causality based approach for quantifying the interactions to aid action classification. Granger causality is used to compute the cause and effect relationships for pairs of motion trajectories of a video. A 2D histogram descriptor for the video is constructed using these pairwise measures. Our proposed method of obtaining pairwise measures for videos is also applicable for large datasets. We have conducted experiments on challenging action recognition databases such as HMDB51 and UCF50 and shown that our causality descriptor helps in encoding additional information regarding the actions and performs on par with the state-of-the art approaches. Due to the complementary nature, a further increase in performance can be observed by combining our approach with state-of-the-art approaches.

Chronic PEGylated obestatin treatment prevents the onset of high fat diet-induced hypertension and endothelial dysfunction in the absence of metabolic actions

Background: Obestatin is a gastrointestinal peptide with established metabolic actions and emerging vascular effects which involve activation of NO signalling. The aim of this study was to investigate effects of a recently-characterised stable analogue, PEGylated obestatin (PEG-OB), in the setting of diet-induced obesity which is associated with both metabolic and vascular dysfunction. Methods: Male Sprague Dawley rats (6 weeks; n=8) were maintained on standard (SD) or high fat (HF) diet (60% fat) for 8 weeks with once-daily injection of either PEG-OB (50nmol/kg/day) or saline from 2 weeks. Results: HF feeding for 8 weeks resulted in marked body weight gain which was not affected by chronic PEG-OB treatment (HF saline, 175.0±12.2; HF PEG-OB, 190.4±6.4g; P=NS). Similarly, blood glucose, as indicated by HbA1c (HF saline, 6.30±0.15; HF PEG-OB, 6.13±0.36%; P=NS) and insulin tolerance (HF saline, 105.2±52.5; HF PEG-OB, 90.3±45.4mmol/L.min; P=NS), were unaltered by PEG-OB. Despite the apparent lack of metabolic effects, chronic PEG-OB treatment markedly attenuated development of HF-induced hypertension (HF saline, 146.5±4.9mmHg; HF PEG-OB, 123.0±9.7mmHg; P<0.01), assessed by tail-cuff plethysmography. Furthermore, organ bath pharmacology in isolated aortic rings, indicated that HF diet-induced endothelial dysfunction was completely prevented by PEG-OB (acetylcholine, EC50: SD saline, 335±113; HF saline, 758±164; HF PEG-OB, 277±85nmol/L; P<0.05). However, contraction to phenylephrine and relaxation to the NO donor, sodium nitroprusside, were unaltered between groups. Conclusions: PEG-OB exerts beneficial effects on hypertension and endothelial function in diabetes independently of metabolic actions suggesting that obestatin signalling may represent a novel therapeutic target to reduce the risk of associated cardiovascular complications.

Unlocking the technology-mediated learning process : insights and articulating actions for an institutional approach

This paper is part of the results from the project "Implementation Strategies and Development of an Open and Distance Education System for the University of the Azores" funded by the European Social Fund. http://hdl.handle.net/10400.3/2327

Neural activation and functional connectivity during motor imagery of bimanual everyday actions

Bimanual actions impose intermanual coordination demands not present during unimanual actions. We investigated the functional neuroanatomical correlates of these coordination demands in motor imagery (MI) of everyday actions using functional magnetic resonance imaging (fMRI). For this, 17 participants imagined unimanual actions with the left and right hand as well as bimanual actions while undergoing fMRI. A univariate fMRI analysis showed no reliable cortical activations specific to bimanual MI, indicating that intermanual coordination demands in MI are not associated with increased neural processing. A functional connectivity analysis based on psychophysiological interactions (PPI), however, revealed marked increases in connectivity between parietal and premotor areas within and between hemispheres. We conclude that in MI of everyday actions intermanual coordination demands are primarily met by changes in connectivity between areas and only moderately, if at all, by changes in the amount of neural activity. These results are the first characterization of the neuroanatomical correlates of bimanual coordination demands in MI. Our findings support the assumed equivalence of overt and imagined actions and highlight the differences between uni- and bimanual actions. The findings extent our understanding of the motor system and may aid the development of clinical neurorehabilitation approaches based on mental practice.

Actions of translocator protein ligands on neutrophil adhesion and motility induced by G-protein coupled receptor signaling

The 18 kDa translocator protein (TSPO) also known as the peripheral benzodiazepine receptor (PBR), mediates the transportation of cholesterol and anions from the outer to the inner mitochondrial membrane in different cells types. Although recent evidences indicate a potential role for TSPO in the development of inflammatory processes, the mechanisms involved have not been elucidated. The present study investigated the ability of the specific TSPO ligands, the isoquinoline carboxamide PK11195 and benzodiazepine Ro5-4864, on neutrophil recruitment promoted by the N-formylmethionyl-leucyl-phenylalanine peptide (fMLP), an agonist of G-protein coupled receptor (GPCR). Pre-treatment with Ro5-4864 abrograted fMLP-induced leukocyte-endothelial interactions in mesenteric postcapillary venules in vivo. Moreover, in vitro Ro5-4864 treatment prevented fMLP-induced: (i) L-selectin shedding and overexpression of PECAM-1 on the neutrophil cell surface; (ii) neutrophil chemotaxis and (iii) enhancement of intracellular calcium cations (iCa(+2)). Intriguingly, the two latter effects were augmented by cell treatment with PK11195. An allosteric agonist/antagonist relation may be suggested, as the effects of Ro5-4864 on fMLP-stimulated neutrophils were reverted by simultaneous treatment with PK11195. Taken together, these data highlight TSPO as a modulator of pathways of neutrophil adhesion and locomotion induced by GPCR, connecting TSPO actions and the onset of an innate inflammatory response. (C) 2011 Elsevier Inc. All rights reserved.

Social inclusion of vulnerable groups through participatory and emancipatory approaches. Implementing active citizenship and socially innovative actions in the framework of civil & human rights model of disability

The research hypothesis of the thesis is that “an open participation in the co-creation of the services and environments, makes life easier for vulnerable groups”; assuming that the participatory and emancipatory approaches are processes of possible actions and changes aimed at facilitating people’s lives. The adoption of these approaches is put forward as the common denominator of social innovative practices that supporting inclusive processes allow a shift from a medical model to a civil and human rights approach to disability. The theoretical basis of this assumption finds support in many principles of Inclusive Education and the main focus of the hypothesis of research is on participation and emancipation as approaches aimed at facing emerging and existing problems related to inclusion. The framework of reference for the research is represented by the perspectives adopted by several international documents concerning policies and interventions to promote and support the leadership and participation of vulnerable groups. In the first part an in-depth analysis of the main academic publications on the central themes of the thesis has been carried out. After investigating the framework of reference, the analysis focuses on the main tools of participatory and emancipatory approaches, which are able to connect with the concepts of active citizenship and social innovation. In the second part two case studies concerning participatory and emancipatory approaches in the areas of concern are presented and analyzed as example of the improvement of inclusion, through the involvement and participation of persons with disability. The research has been developed using a holistic and interdisciplinary approach, aimed at providing a knowledge-base that fosters a shift from a situation of passivity and care towards a new scenario based on the person’s commitment in the elaboration of his/her own project of life.

Review article : ecological approach in studying the relation of perception-action : review of the theoretical and empirical data

In daily activities people are using a number of available means for the achievement of balance, such as the use of hands and the co-ordination of balance. One of the approaches that explains this relationship between perception and action is the ecological theory that is based on the work of a) Bernstein (1967), who imposed the problem of ‘the degrees of freedom’, b) Gibson (1979), who referred to the theory of perception and the way which the information is received from the environment in order for a certain movement to be achieved, c) Newell (1986), who proposed that movement can derive from the interaction of the constraints that imposed from the environment and the organism and d) Kugler, Kelso and Turvey (1982), who showed the way which “the degrees of freedom” are connected and interact. According to the above mentioned theories, the development of movement co-ordination can result from the different constraints that imposed into the organism-environment system. The close relation between the environmental and organismic constraints, as well as their interaction is responsible for the movement system that will be activated. These constraints apart from shaping the co-ordination of specific movements can be a rate limiting factor, to a certain degree, in the acquisition and mastering of a new skill. This frame of work can be an essential tool for the study of catching an object (e.g., a ball). The importance of this study becomes obvious due to the fact that movements that involved in catching an object are representative of every day actions and characteristic of the interaction between perception and action.

Integrating Creative Practice and Research in the Digital Media Arts

Research is often characterised as the search for new ideas and understanding. The language of this view privileges the cognitive and intellectual aspects of discovery. However, in the research process theoretical claims are usually evaluated in practice and, indeed, the observations and experiences of practical circumstances often lead to new research questions. This feedback loop between speculation and experimentation is fundamental to research in many disciplines, and is also appropriate for research in the creative arts. In this chapter we will examine how our creative desire for artistic expressivity results in interplay between actions and ideas that direct the development of techniques and approaches for our audio/visual live-coding activities.

Leading indigenous education in a remote location : reflections on teaching to be "proud and deadly"

This thesis is a critical reflection of the author’s time as a Principal of an Indigenous state school from 2003-2004. The purpose is to reassess the impact of her principalship in terms of the staff, students and Community change that affected learning outcomes at the school and to reanalyse to what actions and to whom positive changes could be attributed. This thesis reflects and identifies, in light of the literature, strategies which were effective in enhancing student learning outcomes. The focus of this thesis was the Doongal State School*, its students, staff and facilities. The author will attempt to draw out theoretical frameworks in terms of: (1) what changed educationally in Doongal State School, (2) what seemed to be important in the Principal’s role, (3) the processes that took place, and (4) the effect of being non- Indigenous and a female. Overall, the author undertook this critical reflection in order to understand and embrace educational practices that will (a) lessen the gap between the academic outcomes achieved by Indigenous and non-Indigenous students, and (b) enhance life choices for Indigenous children. The findings indicate that principal leadership is critical for success in Indigenous schools and is the centrepiece of the models developed to explain improvement at Doongal State School. School factors, Principal Leadership factors, Change factors and factors relating to being a non-Indigenous female principal, which, when implemented, will lead to improved educational outcomes for Indigenous students, have evolved as a result of this thesis. Principal Leadership factors were found to be the enablers for the effective implementation of the key components for success.

Navigating iScapes : Australian youth constructing identities and social relations in a network society

This paper extends Appadurai’s notion of “scapes” to delineate what we see as “iScapes”. We contend that iScapes captures the way online technologies shape interactions that invariably filter into offline contexts, giving shape and meaning to human actions and motivations. By drawing on research on high school students’ online activities we examine the flow of iScapes they inhabit in the process of constructing identities and forming social relations.

Paradigm shifters : tricksters and cultural science

This paper seeks to link anthropological and economic treatments of the process of innovation and change, not only within a given ‘complex system’ (e.g. a cosmology; an industry) but also between systems (e.g. cultural and economic systems; but also divine and human systems). The role of the ‘Go-Between’ is considered, both in the anthropological figure of the Trickster (Hyde 1998) and in the Schumpeterian entrepreneur. Both figures parlay appetite (economic wants) into meaning (cultural signs). Both practice a form of creativity based on deception, ‘creative destruction’; renewal by disruption and needs-must adaptation. The disciplinary purpose of the paper is to try to bridge two otherwise disconnected domains – cultural studies and evolutionary economics – by showing that the traditional methods of the humanities (e.g. anthropological, textual and historical analysis) have explanatory force in the context of economic actions and complex-system evolutionary dynamics. The objective is to understand creative innovation as a general cultural attribute rather than one restricted only to accredited experts such as artists; thus to theorise creativity as a form of emergence for dynamic adaptive systems. In this context, change is led by ‘paradigm shifters’ – tricksters and entrepreneurs who create new meanings out of the clash of difference, including the clash of mutually untranslatable communication systems (language, media, culture).

Academic practice as explanatory framework : reconceptualising international student academic engagement and university teaching

This paper joins growing interest in the concept of practice, and uses it to reconceptualise international student engagement with the demands of study at an Australian university. Practice foregrounds institutional structures and student agency and brings together psychologically- and socially-oriented perspectives on international student learning approaches. Utilising discourse theory, practice is defined as habitual and individual instances of socially-contextualised configurations of elements such as actions and interactions, roles and relations, identities, objects, values, and language. In the university context, academic practice highlights the institutionally-sanctioned ways of knowing, doing and being that constitute academic tasks. The concept is applied here to six international students’ ‘readings’ of and strategic responses to academic work in a Master of Education course. It is argued that academic practice provides a comprehensive framework for explaining the interface between university academic requirements and international student learning, and the crucial role that teaching has in facilitating the experience.

Focusing on patients : differences between the practice of expert and non-expert nephrology nurses

Specialisation in nursing enables a nurse to focus, in much greater depth, on the requisite knowledge and skills for providing patients with the best possible care. Nephrology nursing is one such area where specialisation has evolved. The characteristic focus of practice emerged as an important feature during a study into the process of expertise acquisition in nephrology nursing practice. Using grounded theory methodology, this study involved 6 non-expert and 11 expert nurses and took place in one renal unit in New South Wales. Nephrology nursing practice was observed for 103 hours, and this was immediately followed by semi-structured interviews. The characteristic of focus was conceptualised as the nurses' centre of attention or concentration while they were undertaking nursing activities. Focus ranged from inexperienced non-expert nurses concentrating predominantly on the immediate task at hand, experienced non-expert nurses who focussed on the medium term to expert nurses who viewed actions (and their possible consequences) more broadly and in the longer term. Of significance to nursing, is how nephrology nurses alter their focus of practice as they acquire and exercise their developing expertise in this specialty.

The geometric modelling of social frames and contexts

How do humans respond to their social context? This question is becoming increasingly urgent in a society where democracy requires that the citizens of a country help to decide upon its policy directions, and yet those citizens frequently have very little knowledge of the complex issues that these policies seek to address. Frequently, we find that humans make their decisions more with reference to their social setting, than to the arguments of scientists, academics, and policy makers. It is broadly anticipated that the agent based modelling (ABM) of human behaviour will make it possible to treat such social effects, but we take the position here that a more sophisticated treatment of context will be required in many such models. While notions such as historical context (where the past history of an agent might affect its later actions) and situational context (where the agent will choose a different action in a different situation) abound in ABM scenarios, we will discuss a case of a potentially changing context, where social effects can have a strong influence upon the perceptions of a group of subjects. In particular, we shall discuss a recently reported case where a biased worm in an election debate led to significant distortions in the reports given by participants as to who won the debate (Davis et al 2011). Thus, participants in a different social context drew different conclusions about the perceived winner of the same debate, with associated significant differences among the two groups as to who they would vote for in the coming election. We extend this example to the problem of modelling the likely electoral responses of agents in the context of the climate change debate, and discuss the notion of interference between related questions that might be asked of an agent in a social simulation that was intended to simulate their likely responses. A modelling technology which could account for such strong social contextual effects would benefit regulatory bodies which need to navigate between multiple interests and concerns, and we shall present one viable avenue for constructing such a technology. A geometric approach will be presented, where the internal state of an agent is represented in a vector space, and their social context is naturally modelled as a set of basis states that are chosen with reference to the problem space.