Investigation into the mechanisms responsible for muscle atrophy in cancer cachexia

Cachexia inducing tumours are known to produce a glycoprotein called proteolysis inducing factor (PIF), which induces skeletal muscle atrophy via increased protein degradation and decreased protein synthesis. The objective of this study was to investigate the signalling pathway by which PIF reduces protein synthesis in skeletal muscle and to determine the link, if any, to the ability to induce protein degradation. In murine myotubes PIF induced an increase in expression of the active form of the dsNRA dependent protein kinase (PKR), as well as the phosphorylated form of the translation initiator elF2a, possibly through the release of calcium, at the same concentration as that inhibiting protein synthesis. Inhibition of PKR reversed the inhibition of protein synthesis by PIF and also the induction of protein degradation through the ubiquitin-proteasome pathway by a reduction in the nuclear migration of NK-?B. The expression of phosphorylated forms of PKR and elF2a was also increased in the muscle of cancer patients experiencing weight loss, and in gastrocnemius muscle of mice bearing the cachexia inducing MAC16 tumour, as well as in the tumour itself. Treatment of mice bearing the MAC16 tumour with a PKR inhibitor attenuated muscle atrophy and inhibited tumour growth, through the inactivation of PKR and the consequent reduction of nuclear accumulation of NF-?B. A decreased translational efficiency of the elF-4F complex of initiation factors through dephosphorylation of 4E-BP1 and an increase eEF2 phosphorylation was seen in response to PIF in vitro. The same pattern of events also occurred in gastrocnemius muscle of mice bearing the MAC16 tumour demonstrating weight loss, where a depression of mTOR and p70S6K activation was also observed as weight loss increased.

"Ignorance was bliss, now I'm ignorant and that is far more difficult":transdisciplinary learning and reflexivity in responsible management education

Purpose – The collapse of world economic systems brought the interconnectedness between business and global events sharply into focus. As Starkey points out: “leading business schools need to overcome their fascination with a particular form of finance and economics […] to broaden their intellectual horizons […] (and to) look at the lessons of history and other disciplines”. The purpose of this paper is to provide evidence from three years of research on the Aston MBA suggesting that an emphasis on developing capabilities within a far broader, connected and reflexive business curriculum is what business students and practitioners now recognise as an essential way forward for responsible management education. Design/methodology/approach – This research paper examines the reflective accounts of 300 MBA students undertaking a transdisciplinary Business Ethics, Responsibility and Sustainability core module. Findings – As Klein argues, transdisciplinarity is simultaneously an attitude and a form of action. The student reflections provide powerful discourses of individual learning and report a range of outcomes from finding “the vocabulary or the confidence” to raise issues to acting as “change agents” in the workplace. Originality/value – As responsibility and sustainability requires learners, researchers and educators to engage with real world complexity, uncertainty and risk, conventional disciplinary study, especially within business, often proves inadequate and partial. This paper demonstrates that creative and exploratory frames need to be developed to facilitate the development of more connected knowledge – informed by multiple stakeholders, able to contribute heterogeneous skills, perspectives and expertise.

Bridging difference - national and organisational adaptation for responsible performance

This special issue draws together a selection of articles built around a theme of bridging difference. We argue that the effective transfer of learning across boundaries is crucial in enabling the dissemination of good, and ethical, HR practice. How that transfer might occur, with respect both to the mechanisms to enable or inhibit transfer and to the nature of learning that underpins that transfer, provides the focus of what is discussed here. This is framed against a concern for the nature and future of HRM, in particular its role in ensuring responsible organisational performance. © 2013 Taylor & Francis.

Responsible management education from across the pond:innovations and experiences in UK business schools

The session draws upon experiences highlighted within a series of ongoing CSR/sustainability teaching days organized through the British Academy of Management CSR Special Interest Group, designed to encourage UK schools to develop new innovative curricula and to engage with the UN PRME initiative. The panel will consist of representatives from UK universities all of which are at different stages of developing responsible management curricula and have adopted different approaches towards these challenges.

On the comparative performance of socially responsible and Islamic mutual funds

This is the first study to provide comprehensive analyses of the relative performance of both socially responsible investment (SRI) and Islamic mutual funds. The analysis proceeds in two stages. In the first, the performance of the two categories of funds is measured using partial frontier methods. In the second stage, we use quantile regression techniques.By combining two variants of the Free Disposal Hull (FDH) methods (order-m and order-?) in the first stage of analysis and quantile regression in the second stage, we provide detailed analyses of the impact of different covariates across methods and across different quantiles. In spite of the differences in the screening criteria and portfolio management of both types of funds, variation in the performance is only found for some of the quantiles of the conditional distribution of mutual fund performance. We established that for the most inefficient funds the superior performance of SRI funds is significant. In contrast, for the best mutual funds this evidence vanished and even Islamic funds perform better than SRI.These results show the benefits of performing the analysis using quantile regression.

On the comparative performance of socially responsible and Islamic mutual funds

This is the first study to provide comprehensive analyses of the relative performance of both socially responsible investment (SRI) and Islamic mutual funds. The analysis proceeds in two stages. In the first, the performance of the two categories of funds is measured using partial frontier methods. In the second stage, we use quantile regression techniques. By combining two variants of the Free Disposal Hull (FDH) methods (order- m and order- α) in the first stage of analysis and quantile regression in the second stage, we provide detailed analyses of the impact of different covariates across methods and across different quantiles. In spite of the differences in the screening criteria and portfolio management of both types of funds, variation in the performance is only found for some of the quantiles of the conditional distribution of mutual fund performance. We established that for the most inefficient funds the superior performance of SRI funds is significant. In contrast, for the best mutual funds this evidence vanished and even Islamic funds perform better than SRI. These results show the benefits of performing the analysis using quantile regression. © 2013 Elsevier B.V.

Do ethics imply persistence? The case of Islamic and socially responsible funds

We analyse the performance persistence of Islamic and Socially Responsible Investment (SRI) mutual funds. We adopt a multi-stage strategy in which, in the first stage, partial frontiers’ approaches are considered to measure the performance of the different funds in the sample. In the second stage, the results yielded by the partial frontiers are plugged into different investment strategies based on a recursive estimation methodology whose persistence performance is evaluated in the third stage of the analysis. Results indicate that, for both types of funds, performance persistence actually exists, but only for the worst and, most notably, best funds. This result is robust not only across methods (and different choices of tuning parameters within each method) but also across both SRI and Islamic funds—although in the case of the latter persistence was stronger for the best funds. The persistence of SRI and Islamic funds represents an important result for investors and the market, since it provides information on both which funds to invest in and which funds to avoid. Last but not least, the use of the aforementioned techniques in the context of mutual funds could also be of interest for the non-conclusive literature.

Are tumoral factors responsible for host tissue wasting in cancer cachexia?

Both cytokines and tumor factors have been implicated in tissue loss in cancercachexia. Loss of adipose tissue is most likely due to the tumor (and host) factorzinc-α2-glycoprotein because of its direct lipolytic effect, ability to sensitizeadipocytes to lipolytic stimuli and increased expression in cachexia. TNF-α andthe tumor factor proteolysis-inducing factor are the major contenders for skeletalmuscle at rophy; both increase protein degradat ion through theubiquitin-proteasome pathway and depres s protein synthesis throughphosphorylation of eukaryotic initiation factor 2α. However, while most studiesreport proteolysis-inducing factor levels to correlate with the appearance ofcachexia, there is some disagreement regarding a correlation between serumlevels of TNF-α and weight loss. Furthermore, only antagonists to proteolysisinducingfactor prevent muscle loss in cancer patients, suggesting that tumorfactors are the most important. © 2010 Future Medicine Ltd.