Alternative dispute resolution : are apology and forgiveness simply two sides of the one coin?

Alternative dispute resolution (a.d.r.) processes are entrenched in western style legal systems. Forms of dispute resolution are utilised within schools and health systems; built in to commercial contracts; found in workplaces, clubs and organisations; and accepted in general day-to-day community disputes. The a.d.r. literature includes references to ‘apology’, but is largely silent on ‘forgiveness’. Where an apology is offered as part of a dispute resolution process, practice suggests that formalised ‘forgiveness’ rarely follows. Mediators may agree there is a meaningful place for apology in dispute resolution processes, but are most unlikely to support a view that forgiveness, as a conscious act, has an equivalent place. Yet, if forgiveness is not limited to the ‘pardoning of an offence’, but includes a ‘giving up of resentment’, or the relinquishing of a grudge, then forgiveness may play an underestimated role in dispute management. In the context of some day-to-day dispute management practice, this paper questions whether forgiveness should follow an apology; and concludes that meaningful resolutions can be reached without any formal element of ‘forgiveness’ or absolution. However, dispute management practitioners need to be aware of the latent role other aspects of forgiveness may play for the disputing parties.

Noising around : investigations in mobile learning

In this paper we present an account of children's interactions with a mobile technology prototype within a school context. The Noise Detectives trial was conducted in a school setting with the aim of better understanding the role of mobile technology as a mediator within science learning activities. Over eighty children, aged between ten and twelve, completed an outdoor data gathering activity using a mobile learning prototype that included paper and digital components. They measured and recorded noise levels at a range of locations throughout the schools. We analyzed the activity to determine how the components of the prototype were integrated into the learning activity, and to identify differences in behavior that resulted from using these components. We present design implications that resulted from observed differences in prototype use and appropriation.

The mediating effects of the time structure on the relationships between time management behaviour, job satisfaction and psychological wellbeing

This article examined the relationship between time structure and Macan's process model of time management. This study proposed that time structure—‘appraisal of effective time usage’—would be a more parsimonious mediator than perceived control over time in the relationship between time management behaviours and outcome variables, such as job satisfaction and psychological well-being. Alternative structure models were compared using a sample of 111 university students. Model 1 tested Macan's process model of time management with perceived control over time as the mediator. Model 2 replaced perceived control over time by the construct of time structure. Model 3 examined the possibility of perceived control over time and time structure as being parallel mediators of the relationships between time management and outcomes. Results of this study showed that Model 1 and Model 2 fitted the data equally well. On the other hand, the mediated effects were small and partial in both models. This pattern of results calls for reassessment of the process model.

Critical literacy finds a "Place": Writing and social action in a low-income Australian grade 2/3 classroom

In a study of socioeconomically disadvantaged children's acquisition of school literacies, a university research team investigated how a group of teachers negotiated critical literacies and explored notions of social power with elementary children in a suburban school located in an area of high poverty. Here we focus on a grade 2/3 classroom where the teacher and children became involved in a local urban renewal project and on how in the process the children wrote about place and power. Using the students' concerns about their neighborhood, the teacher engaged her class in a critical literacy project that not only involved a complex set of literate practices but also taught the children about power and the possibilities for local civic action. In particular, we discuss examples of children's drawing and writing about their neighborhoods and their lives. We explore how children's writing and drawing might be key elements in developing "critical literacies" in elementary school settings. We consider how such classroom writing can be a mediator of emotions, intellectual and academic learning, social practice, and political activism.

Conceptualising use for information systems (IS) success

This thesis conceptualises Use for IS (Information Systems) success. While Use in this study describes the extent to which an IS is incorporated into the user’s processes or tasks, success of an IS is the measure of the degree to which the person using the system is better off. For IS success, the conceptualisation of Use offers new perspectives on describing and measuring Use. We test the philosophies of the conceptualisation using empirical evidence in an Enterprise Systems (ES) context. Results from the empirical analysis contribute insights to the existing body of knowledge on the role of Use and demonstrate Use as an important factor and measure of IS success. System Use is a central theme in IS research. For instance, Use is regarded as an important dimension of IS success. Despite its recognition, the Use dimension of IS success reportedly suffers from an all too simplistic definition, misconception, poor specification of its complex nature, and an inadequacy of measurement approaches (Bokhari 2005; DeLone and McLean 2003; Zigurs 1993). Given the above, Burton-Jones and Straub (2006) urge scholars to revisit the concept of system Use, consider a stronger theoretical treatment, and submit the construct to further validation in its intended nomological net. On those considerations, this study re-conceptualises Use for IS success. The new conceptualisation adopts a work-process system-centric lens and draws upon the characteristics of modern system types, key user groups and their information needs, and the incorporation of IS in work processes. With these characteristics, the definition of Use and how it may be measured is systematically established. Use is conceptualised as a second-order measurement construct determined by three sub-dimensions: attitude of its users, depth, and amount of Use. The construct is positioned in a modified IS success research model, in an attempt to demonstrate its central role in determining IS success in an ES setting. A two-stage mixed-methods research design—incorporating a sequential explanatory strategy—was adopted to collect empirical data and to test the research model. The first empirical investigation involved an experiment and a survey of ES end users at a leading tertiary education institute in Australia. The second, a qualitative investigation, involved a series of interviews with real-world operational managers in large Indian private-sector companies to canvass their day-to-day experiences with ES. The research strategy adopted has a stronger quantitative leaning. The survey analysis results demonstrate the aptness of Use as an antecedent and a consequence of IS success, and furthermore, as a mediator between the quality of IS and the impacts of IS on individuals. Qualitative data analysis on the other hand, is used to derive a framework for classifying the diversity of ES Use behaviour. The qualitative results establish that workers Use IS in their context to orientate, negotiate, or innovate. The implications are twofold. For research, this study contributes to cumulative IS success knowledge an approach for defining, contextualising, measuring, and validating Use. For practice, research findings not only provide insights for educators when incorporating ES for higher education, but also demonstrate how operational managers incorporate ES into their work practices. Research findings leave the way open for future, larger-scale research into how industry practitioners interact with an ES to complete their work in varied organisational environments.

An examination of the relationships between lifestyle factors and mental health among Australian midlife and older women

Background It is well known that lifestyle factors including overweight/obesity, physical inactivity, smoking and alcohol use are largely related with morbidity and mortality of chronic diseases including diabetes and cardiovascular diseases. The effect of lifestyle factors on people’s mental health who have a chronic disease is less defined in the research. The World Health Organisation has defined health as “a state of complete physical, mental and social well-being”. It is important, therefore to develop an understanding of the relationships between lifestyle and mental health as this may have implications for maximising the efficacy of health promotion in people with chronic diseases. Objectives The overall aim of the research was to examine the relationships between lifestyle factors and mental health among Australian midlife and older women. Methodology The current research measured four lifestyle factors including weight status, physical activity, smoking and alcohol use. Three interconnecting studies were undertaken to develop a comprehensive understanding of the relationships between lifestyle factors and mental health. Study 1 investigated the longitudinal effect of lifestyle factors on mental health by using midlife and older women randomly selected from the community. Study 2 adopted a cross-sectional design, and compared the effect of lifestyle factors on mental health between midlife and older women with and without diabetes. Study 3 examined the mediating effect of self-efficacy in the relationships between lifestyle factors and mental health among midlife and older women with diabetes. A questionnaire survey was chosen as the means to gather information, and multiple linear regression analysis was conducted as the primary statistical approach. Results The research showed that the four lifestyle factors including weight status, physical activity, smoking and alcohol use did impact on mental health among Australian midlife and older women. First, women with a higher BMI had lower levels of mental health than women with normal weight, but as women age, the mental health of women who were overweight and obese becomes better than that of women with normal weight. Second, women who were physically active had higher levels of mental health than those who were not. Third, smoking adversely impacted on women’s mental health. Finally, those who were past-drinkers had less anxiety symptoms than women who were non-drinkers as they age. Women with diabetes appeared to have lower levels of mental health compared to women without. However, the disparities of mental health between two groups were confounded by low levels of physical activity and co-morbidities. This finding underlines the effect of physical activity on women’s mental health, and highlights the potential of reducing the gap of mental health by promoting physical activity. In addition, self-efficacy was shown to be the mediator of the relationships between BMI, physical activity and depression, suggesting that enhancing people’s self-efficacy may be useful for mental health improvement. Conclusions In conclusion, Australian midlife and older women who live with a healthier lifestyle have higher levels of mental health. It is suggested that strategies aiming to improve people’s mental health may be more effective if they focus on enhancing people’s self-efficacy levels. This study has implications to both health education and policy development. It indicates that health professionals may need to consider clients’ mental health as an integrated part of lifestyle changing process. Furthermore, given that lifestyle factors impact on both physical and mental health, lifestyle modification should continue to be the focus of policy development.

Determinants of skin self-examination (SSE) in men aged 50 years or older

Background: Queensland men aged 50 years and older are at high risk for melanoma. Early detection via skin self examination (SSE) (particularly whole-body SSE) followed by presentation to a doctor with suspicious lesions, may decrease morbidity and mortality from melanoma. Prevalence of whole-body SSE (wbSSE) is lower in Queensland older men compared to other population subgroups. With the exception of the present study no previous research has investigated the determinants of wbSSE in older men, or interventions to increase the behaviour in this population. Furthermore, although past SSE intervention studies for other populations have cited health behaviour models in the development of interventions, no study has tested these models in full. The Skin Awareness Study: A recent randomised trial, called the Skin Awareness Study, tested the impact of a video-delivered intervention compared to written materials alone on wbSSE in men aged 50 years or older (n=930). Men were recruited from the general population and interviewed over the telephone at baseline and 13 months. The proportion of men who reported wbSSE rose from 10% to 31% in the control group, and from 11% to 36% in the intervention group. Current research: The current research was a secondary analysis of data collected for the Skin Awareness Study. The objectives were as follows: • To describe how men who did not take up any SSE during the study period differed from those who did take up examining their skin. • To determine whether the intervention program was successful in affecting the constructs of the Health Belief Model it was aimed at (self-efficacy, perceived threat, and outcome expectations); and whether this in turn influenced wbSSE. • To determine whether the Health Action Process Approach (HAPA) was a better predictor of wbSSE behaviour compared to the Health Belief Model (HBM). Methods: For objective 1, men who did not report any past SSE at baseline (n=308) were categorised as having ‘taken up SSE’ (reported SSE at study end) or ‘resisted SSE’ (reported no SSE at study end). Bivariate logistic regression, followed by multivariable regression, investigated the association between participant characteristics measured at baseline and resisting SSE. For objective 2 proxy measures of self-efficacy, perceived threat, and outcome expectations were selected. To determine whether these mediated the effect of the intervention on the outcome, a mediator analysis was performed with all participants who completed interviews at both time points (n=830) following the Baron and Kenny approach, modified for use with structural equation modelling (SEM). For objective 3, control group participants only were included (n=410). Proxy measures of all HBM and HAPA constructs were selected and SEM was used to build up models and test the significance of each hypothesised pathway. A likelihood ratio test compared the HAPA to the HBM. Results: Amongst men who did not report any SSE at baseline, 27% did not take up any SSE by the end of the study. In multivariable analyses, resisting SSE was associated with having more freckly skin (p=0.027); being unsure about the statement ‘if I saw something suspicious on my skin, I’d go to the doctor straight away’ (p=0.028); not intending to perform SSE (p=0.015), having lower SSE self-efficacy (p<0.001), and having no recommendation for SSE from a doctor (p=0.002). In the mediator analysis none of the tested variables mediated the relationship between the intervention and wbSSE. In regards to health behaviour models, the HBM did not predict wbSSE well overall. Only the construct of self-efficacy was a significant predictor of future wbSSE (p=0.001), while neither perceived threat (p=0.584) nor outcome expectations (p=0.220) were. By contrast, when the HAPA constructs were added, all three HBM variables predicted intention to perform SSE, which in turn predicted future behaviour (p=0.015). The HAPA construct of volitional self-efficacy was also associated with wbSSE (p=0.046). The HAPA was a significantly better model compared to the HBM (p<0.001). Limitations: Items selected to measure HBM and HAPA model constructs for objectives 2 and 3 may not have accurately reflected each construct. Conclusions: This research added to the evidence base on how best to target interventions to older men; and on the appropriateness of particular health behaviour models to guide interventions. Findings indicate that to overcome resistance those men with more negative pre-existing attitudes to SSE (not intending to do it, lower initial self-efficacy) may need to be targeted with more intensive interventions in the future. Involving general practitioners in recommending SSE to their patients in this population, alongside disseminating an intervention, may increase its success. Comparison of the HBM and HAPA showed that while two of the three HBM variables examined did not directly predict future wbSSE, all three were associated with intention to self-examine skin. This suggests that in this population, intervening on these variables may increase intention to examine skin, but not necessarily the behaviour itself. Future interventions could potentially focus on increasing both the motivational variables of perceived threat and outcome expectations as well as a combination of both action and volitional self-efficacy; with the aim of increasing intention as well as its translation to taking up and maintaining regular wbSSE.

Work-Related Subjective Experiences, Work-Related Self-Efficacy, and Career Learning Among People with Psychiatric Disabilities

Work-related subjective experiences and work-related self-efficacy were investigated as candidate correlates of career learning among people with schizophrenia and schizoaffective disorder. Work-related self-efficacy was expected to mediate any observed relationship between work-related subjective experiences and employment status, after controlling for demographic, vocational, and clinical covariates. Baseline measures (n 1 = 104) were repeated at six months (n 2 = 94) and 12 months (n 3 = 94). Work-related subjective experiences and work-related self-efficacy were consistently associated with current employment after controlling for covariates. The proposed mediator role of work-related self-efficacy remains a viable hypothesis requiring further investigation. Both work-related subjective experiences and work-related self-efficacy appear promising as components of the social cognitive career learning theory to help explain career development among people with psychiatric disabilities.

The relationship between parents’ self-efficacy beliefs, outcome expectations, child behaviour, and management of atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin condition, characterized by intense pruritis, with a complex aetiology comprising multiple genetic and environmental factors. It is a common chronic health problem among children, and along with other allergic conditions, is increasing in prevalence within Australia and in many countries worldwide. Successful management of childhood AD poses a significant and ongoing challenge to parents of affected children. Episodic and unpredictable, AD can have profound effects on children’s physical and psychosocial wellbeing and quality of life, and that of their caregivers and families. Where concurrent child behavioural problems and parenting difficulties exist, parents may have particular difficulty achieving adequate and consistent performance of the routine management tasks that promote the child’s health and wellbeing. Despite frequent reports of behaviour problems in children with AD, past research has neglected the importance of child behaviour to parenting confidence and competence with treatment. Parents of children with AD are also at risk of experiencing depression, anxiety, parenting stress, and parenting difficulties. Although these factors have been associated with difficulty in managing other childhood chronic health conditions, the nature of these relationships in the context of child AD management has not been reported. This study therefore examined relationships between child, parent, and family variables, and parents’ management of child AD and difficult child behaviour, using social cognitive and self-efficacy theory as a guiding framework. The study was conducted in three phases. It employed a quantitative, cross-sectional study design, accessing a community sample of 120 parents of children with AD, and a sample of 64 child-parent dyads recruited from a metropolitan paediatric tertiary referral centre. In Phase One, instruments designed to measure parents’ self-reported performance of AD management tasks (Parents’ Eczema Management Scale – PEMS) and parents’ outcome expectations of task performance (Parents’ Outcome Expectations of Eczema Management Scale – POEEMS) were adapted from the Parental Self-Efficacy with Eczema Care Index (PASECI). In Phase Two, these instruments were used to examine relationships between child, parent, and family variables, and parents’ self-efficacy, outcome expectations, and self-reported performance of AD management tasks. Relationships between child, parent, and family variables, parents’ self-efficacy for managing problem behaviours, and reported parenting practices, were also examined. This latter focus was explored further in Phase Three, in which relationships between observed child and parent behaviour, and parent-reported self-efficacy for managing both child AD and problem behaviours, were explored. Phase One demonstrated the reliability of both PEMS and POEEMS, and confirmed that PASECI was reliable and valid with modification as detailed. Factor analyses revealed two-factor structures for PEMS and PASECI alike, with both scales containing factors related to performing routine management tasks, and managing the child’s symptoms and behaviour. Factor analysis was also applied to POEEMS resulting in a three-factor structure. Factors relating to independent management of AD by the parent, involving healthcare professionals in management, and involving the child in management of AD were found. Parents’ self-efficacy and outcome expectations had a significant influence on self-reported task performance. In Phase Two, relationships emerged between parents’ self-efficacy and self-reported performance of AD management tasks, and AD severity, child behaviour difficulties, parent depression and stress, conflict over parenting issues, and parents’ relationship satisfaction. Using multiple linear regressions, significant proportions of variation in parents’ self-efficacy and self-reported performance of AD management tasks were explained by child behaviour difficulties and parents’ formal education, and self-efficacy emerged as a likely mediator for the relationships between both child behaviour and parents’ education, and performance of AD management tasks. Relationships were also found between parents’ self-efficacy for managing difficult child behaviour and use of dysfunctional parenting strategies, and child behaviour difficulties, parents’ depression and stress, conflict over parenting issues, and relationship satisfaction. While significant proportions of variation in self-efficacy for managing child behaviour were explained by both child behaviour and family income, family income was the only variable to explain a significant proportion of variation in parent-reported use of dysfunctional parenting strategies. Greater use of dysfunctional parenting strategies (both lax and authoritarian parenting) was associated with more severe AD. Parents reporting lower self-efficacy for managing AD also reported lower self-efficacy for managing difficult child behaviour; likewise, less successful self-reported performance of AD management tasks was associated with greater use of dysfunctional parenting strategies. When child and parent behaviour was directly observed in Phase Three, more aversive child behaviour was associated with lower self-efficacy, less positive outcome expectations, and poorer self-reported performance of AD management tasks by parents. Importantly, there were strong positive relationships between these variables (self-efficacy, outcome expectations, and self-reported task performance) and parents’ observed competence when providing treatment to their child. Less competent performance was also associated with greater parent-reported child behaviour difficulties, parent depression and stress, parenting conflict, and relationship dissatisfaction. Overall, this study revealed the importance of child behaviour to parents’ confidence and practices in the contexts of child AD and child behaviour management. Parents of children with concurrent AD and behavioural problems are at particular risk of having low self-efficacy for managing their child’s AD and difficult behaviour. Children with more severe AD are also at higher risk of behaviour problems, and thus represent a high-risk group of children whose parents may struggle to manage the disease successfully. As one of the first studies to examine the role and correlates of parents’ self-efficacy in child AD management, this study identified a number of potentially modifiable factors that can be targeted to enhance parents’ self-efficacy, and improve parent management of child AD. In particular, interventions should focus on child behaviour and parenting issues to support parents caring for children with AD and improve child health outcomes. In future, findings from this research will assist healthcare teams to identify parents most in need of support and intervention, and inform the development and testing of targeted multidisciplinary strategies to support parents caring for children with AD.

Computational design of cyclic nitroxides as efficient redox mediators for dye-sensitized solar cells

Cyclic nitroxide radicals represent promising alternatives to the iodine-based redox mediator commonly used in dye-sensitized solar cells (DSSCs). To date DSSCs with nitroxide-based redox mediators have achieved energy conversion efficiencies of just over 5 % but efficiencies of over 15 % might be achievable, given an appropriate mediator. The efficacy of the mediator depends upon two main factors: it must reversibly undergo one-electron oxidation and it must possess an oxidation potential in a range of 0.600-0.850 V (vs. a standard hydrogen electrode (SHE) in acetonitrile at 25 °C). Herein, we have examined the effect that structural modifications have on the value of the oxidation potential of cyclic nitroxides as well as the reversibility of the oxidation process. These included alterations to the N-containing skeleton (pyrrolidine, piperidine, isoindoline, azaphenalene, etc.), as well as the introduction of different substituents (alkyl-, methoxy-, amino-, carboxy-, etc.) to the ring. Standard oxidation potentials were calculated using high-level ab initio methodology that was demonstrated to be very accurate (with a mean absolute deviation from experimental values of only 16 mV). An optimal value of 1.45 for the electrostatic scaling factor for UAKS radii in acetonitrile solution was obtained. Established trends in the values of oxidation potentials were used to guide molecular design of stable nitroxides with desired E° ox and a number of compounds were suggested for potential use as enhanced redox mediators in DSSCs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms

Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4+ and CD8+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1−/− mice or in mice depleted of CD4+ and/or CD8+ cells than in normal mice. The tumors in RAG1−/− mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

Nitric oxide synthase type-II is synthesized by human gingival tissue and cultured human gingival fibroblasts

Nitric oxide is known to be an important inflammatory mediator, and is implicated in the pathophysiology of a range of inflammatory disorders. The aim of this study was to determine the localization and distribution of endothelial NOS (NOS-II) in human gingival tissue, and to ascertain if human gingival fibroblasts express NOS-II when stimulated with interferon gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS). The distribution of NOS-II in inflamed and non-inflamed specimens of human gingivae was studied using a monoclonal antibody against nitric oxide synthase II. Cultures of fibroblasts derived from healthy human gingivae were used for the cell culture experiments. The results from immunohistochemical staining of the tissues indicated an upregulation of NOS-II expression in inflamed compared to non-inflamed gingival tissue. Fibroblasts and inflammatory cells within the inflamed connective tissue were positively stained for NOS-II. In addition, basal keratinocytes also stained strongly for NOS-II, in both healthy and inflamed tissue sections. When cultured human gingival fibroblasts were stimulated by INF-gamma and Porphyromonas gingivalis LPS, NOS-II was more strongly expressed than when the cells were exposed to LPS or IFN-gamma alone. These data suggest that, as for other inflammatory diseases, NO plays a role in the pathophysiology of periodontitis.

Many paths lead to discovery : analogical retrieval of cancer therapies

This paper addresses the issue of analogical inference, and its potential role as the mediator of new therapeutic discoveries, by using disjunction operators based on quantum connectives to combine many potential reasoning pathways into a single search expression. In it, we extend our previous work in which we developed an approach to analogical retrieval using the Predication-based Semantic Indexing (PSI) model, which encodes both concepts and the relationships between them in high-dimensional vector space. As in our previous work, we leverage the ability of PSI to infer predicate pathways connecting two example concepts, in this case comprising of known therapeutic relationships. For example, given that drug x TREATS disease z, we might infer the predicate pathway drug x INTERACTS WITH gene y ASSOCIATED WITH disease z, and use this pathway to search for drugs related to another disease in similar ways. As biological systems tend to be characterized by networks of relationships, we evaluate the ability of quantum-inspired operators to mediate inference and retrieval across multiple relations, by testing the ability of different approaches to recover known therapeutic relationships. In addition, we introduce a novel complex vector based implementation of PSI, based on Plate’s Circular Holographic Reduced Representations, which we utilize for all experiments in addition to the binary vector based approach we have applied in our previous research.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

BSTA Promotes mTORC2-Mediated Phosphorylation of Akt1 to Suppress Expression of FoxC2 and Stimulate Adipocyte Differentiation

Phosphorylation and activation of Akt1 is a crucial signaling event that promotes adipogenesis. However, neither the complex multistep process that leads to activation of Akt1 through phosphorylation at Thr308 and Ser473 nor the mechanism by which Akt1 stimulates adipogenesis is fully understood. We found that the BSD domain–containing signal transducer and Akt interactor (BSTA) promoted phosphorylation of Akt1 at Ser473 in various human and murine cells, and we uncovered a function for the BSD domain in BSTA-Akt1 complex formation. The mammalian target of rapamycin complex 2 (mTORC2) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation. Furthermore, analyses of bsta gene-trap murine embryonic stem cells revealed an essential function for BSTA and phosphorylation of Akt1 at Ser473 in promoting adipocyte differentiation, which required suppression of the expression of the gene encoding the transcription factor FoxC2. These findings indicate that BSTA is a molecular switch that promotes phosphorylation of Akt1 at Ser473 and reveal an mTORC2-BSTA-Akt1-FoxC2–mediated signaling mechanism that is critical for adipocyte differentiation.