Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway

The use of adherent monolayer cultures have produced many insights into melanoma cell growth and differentiation, but often novel therapeutics demonstrated to act on these cells are not active in vivo. It is imperative that new methods of growing melanoma cells that reflect growth in vivo are investigated. To this end, a range of human melanoma cell lines passaged as adherent cultures or induced to form melanoma spheres (melanospheres) in stem cell media have been studied to compare cellular characteristics and protein expression. Melanoma spheres and tumours grown from cell lines as mouse xenografts had increased heterogeneity when compared with adherent cells and 3D-spheroids in agar (aggregates). Furthermore, cells within the melanoma spheres and mouse xenografts each displayed a high level of reciprocal BRN2 or MITF expression, which matched more closely the pattern seen in human melanoma tumours in situ, rather than the propensity for co-expression of these important melanocytic transcription factors seen in adherent cells and 3D-spheroids. Notably, when the levels of the BRN2 and MITF proteins were each independently repressed using siRNA treatment of adherent melanoma cells, members of the NOTCH pathway responded by decreasing or increasing expression, respectively. This links BRN2 as an activator, and conversely, MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability, cell adhesion during 3D-spheroid formation and invasion through a collagen matrix. Combined, this evidence suggests that the melanoma sphere-culture system induces subpopulations of cells that may more accurately portray the in vivo disease, than the growth as adherent melanoma cells.

Book review : "Carbon Capture and Storage Emerging Legal and Regulatory Issues" edited by Ian Havercroft, Richard Macrory, Richard B Stewart, Oxford, Hart Publishing, 2011

As the international community struggles to find a cost-effective solution to mitigate climate change and reduce greenhouse gas emissions, carbon capture and storage (CCS) has emerged as a project mechanism with the potential to assist in transitioning society towards its low carbon future. Being a politically attractive option, legal regimes to promote and approve CCS have proceeded at an accelerated pace in multiple jurisdictions including the European Union and Australia. This acceleration and emphasis on the swift commercial deployment of CCS projects has left the legal community in the undesirable position of having to advise on the strengths and weaknesses of the key features of these regimes once they have been passed and become operational. This is an area where environmental law principles are tested to their very limit. On the one hand, implementation of this new technology should proceed in a precautionary manner to avoid adverse impacts on the atmosphere, local community and broader environment. On the other hand, excessive regulatory restrictions will stifle innovation and act as a barrier to the swift deployment of CCS projects around the world. Finding the balance between precaution and innovation is no easy feat. This is an area where lawyers, academics, regulators and industry representatives can benefit from the sharing of collective experiences, both positive and negative, across the jurisdictions. This exemplary book appears to have been collated with this philosophy in mind and provides an insightful addition to the global dialogue on establishing effective national and international regimes for the implementation of CCS projects...

Chinese online literature : creative consumers and evolving business models

Purpose – The internet is transforming possibilities for creative interaction, experimentation and cultural consumption in China and raising important questions about the role that “publishers” might play in an open and networked digital world. The purpose of this paper is to consider the role that copyright is playing in the growth of a publishing industry that is being “born digital”. Design/methodology/approach – The paper approaches online literature as an example of a creative industry that is generating value for a wider creative economy through its social network market functions. It builds on the social network market definition of the creative industries proposed by Potts et al. and uses this definition to interrogate the role that copyright plays in a rapidly-evolving creative economy. Findings – The rapid growth of a market for crowd-sourced content is combining with growing commercial freedom in cultural space to produce a dynamic landscape of business model experimentation. Using the social web to engage audiences, generate content, establish popularity and build reputation and then converting those assets into profit through less networked channels appears to be a driving strategy in the expansion of wider creative industries markets in China. Originality/value – At a moment when publishing industries all over the world are struggling to come to terms with digital technology, the emergence of a rapidly-growing area of publishing that is being born digital offers important clues about the future of publishing and what social network markets might mean for the role of copyright in a digital age.

Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?

Objective: We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention. Design: 16 obese men and women (41 ± 9 years; BMI 39 ± 6 kg/m2) were investigated in energy balance before, after and twice during a 12-week VLED (565–650 kcal/day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74-87%). Body composition was measured by deuterium dilution and DXA and resting metabolic rate (RMR) by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants: 9.45 kcal/gFM and 1.13 kcal/gFFM. Predicted weight loss was calculated from the energy deficit using the '7700 kcal/kg rule'. Results: Changes in weight (-18.6 ± 5.0 kg), FM (-15.5 ± 4.3 kg), and FFM (-3.1 ± 1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39 to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01) and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of predicted values. Conclusion: Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. While lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic down-regulation should not be discounted.

From homepages to network profiles : balancing personal and social identity

The World Wide Web constitutes one of the most important inventions of the late 20th century: it has changed culture, society, business, communication, politics, and many other fields of human endeavour, not least also by providing a more user-friendly pathway of access to its major underlying technology, the Internet itself. Key phases in its development can be charted, especially by how it has been used to present and share information – and here, the personal or professional, private or official homepage stands in as a useful representation of wider Web trends overall. From hand-coded beginnings through several successive stages of experimentation and standardisation, to the shifting balance between personal sites and social networks, the homepage demonstrates how the Web itself, and its place in our lives, have changed.

Content analysis of international research in geographical and environmental education : eighteen years of academic publishing

This paper examines the history of the IRGEE Journal in terms of its sustainable future. The development of geographical and environmental education is evaluated, as reflected from the articles published in the Journal “International Research in Geographical and Environmental Education” (IRGEE). A content analysis of all papers and forum sections which have appeared in the journal since Volume 1 Number 1 was published in 1992 has been conducted, examining the content of as many as 526 articles. The method was a content analysis, and revealed themes which have experienced an increasing or declining interest over the 18 years of publication of IRGEE (1992-2009), while other themes have remained current during this period. The main findings of this analysis are: a) the total number of articles has increased more than threefold, b) articles related to geographical education (sensu stricto) outweighed those related to environmental education, c) the themes “syllabi, textbooks, curricula” and “values, attitudes” attract the attention of researchers with increasing strength and d) emerging subjects, such as GIS and sustainability have appeared dynamically in the last years.

Critical discourse analysis and political economy of communication : understanding the new corporate order

This article uses critical discourse analysis to analyse material shifts in the political economy of communications. It examines texts of major corporations to describe four key changes in political economy: (1) the separation of ownership from control; (2) the separation of business from industry; (3) the separation of accountability from responsibility; and (4) the subjugation of ‘going concerns’ by overriding concerns. The authors argue that this amounts to a political economic shift from traditional concepts of ‘capitalism’ to a new ‘corporatism’ in which the relationships between public and private, state and individual interests have become redefined and obscured through new discourse strategies. They conclude that the present financial and regulatory ‘crisis’ cannot be adequately resolved without a new analytic framework for examining the relationships between corporation, discourse and political economy.

Knowledge unlatched : towards an open and networked future for academic publishing

Specialist book length publications in the humanities and social sciences (including but not exclusively monographs) are experiencing a crisis. It is clear that the current publishing system is failing both the producers and users of scholarship and neglects many of the opportunities associated with networked culture.

Book Review : Criminological and Legal Consequences of Climate Change. Edited by Stephen Farrell, Tawhida Ahmed and Duncan French (Oxford : Hart Publishing, 272 pp.)

The book addresses a number of pressing social and environmental issues of global concern. It takes the reader on a socio-legal journal of climate change and explores a range of challenging and complex topics including renewable energies, emissions reduction, carbon trading, deforestation, migration and corporate governance.

Access to East European and Eurasian culture : publishing, acquisitions, digitization, metadata

Review of the book 'Access to East European and Eurasian culture: publishing, acquisitions, digitization, metadata', edited by Miranda Remnek, published by Haworth Information Press, 2009.

Labour market institutions and the gender wage gap in Britain and Australia, 1973–90

The importance of wage structure is frequently interpreted as indirect evidence of the role played by labour market institutions. The current paper follows in this tradition, examining the role of wage structure in explaining the trend in the gender wage gap over the period 1973–91 for both Australia and the UK. The focus is upon whether changes in wage structure (and associated gender wage gap) both across country and over time are compatible with institutional explanations. Combining comparisons both cross-country and over time yields a more stringent, albeit indirect, test of the role of institutions.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

BACKGROUND/OBJECTIVEs A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). SUBJECTS/METHODS Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m2) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m2). RESULTS Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (−102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=−0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=−0.44; P=0.01). CONCLUSIONS Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Business Innovation and Disruption in Publishing

This is the first volume in a book series examining how organizations in the creative industries respond to disruptive change and how they themselves generate business innovations. The aspiration of this book series is to understand some of the common forces behind the disruptions occurring in so many creative industries today and identifying the most promising strategies and responses by organizations to create new value propositions, business models and business practices that can enable these industry participants to cope with and eventually thrive as their industries and sectors are transformed. The chapters included in the volume examine the processes of disruption and transformation due to the technology of the Internet, social forces driven by social media, the development of new portable digital devices with greater capabilities and smaller size, the decreasing costs of new information, and the creation of new business models and forms of intellectual property ownership rights for a digitized industry. The context for this volume is the publishing industries, understood as the industries for the publishing of fiction and non-fiction books, academic literature, consumer as well as trade magazines, and daily newspapers. This volume includes chapters by an internationally diverse array of media scholars whose chapters provide insights into these phenomena in Eastern Europe, Finland, France, Germany, Norway, Portugal, Russia, and the United States, using different methodological frameworks including, but not limited to, surveys, in-depth interviews and multiple-case studies. One gap that this book series seeks to fill is that between the study of business innovation and disruption by innovation scholars largely based in business school settings and similar studies by scholarly experts from non-business school disciplines, including the broader social sciences (e.g. sociology, political science, economic geography) and creative industry based professional school disciplines (e.g. architecture, communications, design, film making, journalism, media studies, performing arts, photography and television). Future volumes of this book series will examine disruption and business innovation in the film, video and photography sectors (volume two), the music sector (volume three) and interactive entertainment (volume four), with subsequent volumes focusing on the most relevant developments in creative industry business innovation and disruption that emerge.

Selective regulation of p38β protein and signaling by integrin-linked kinase mediates bladder cancer cell migration

Integrin-linked kinase (ILK) and p38MAPK are protein kinases that transduce extracellular signals regulating cell migration and actin cytoskeletal organization. ILK-dependent regulation of p38MAPK is critical for mammalian kidney development and in smooth muscle cell migration, however, specific p38 isoforms has not been previously examined in ILK-regulated responses. Signaling by ILK and p38MAPK is often dysregulated in bladder cancer, and here we report a strong positive correlation between protein levels of ILK and p38β, which is the predominant isoform found in bladder cancer cells, as well as in patient-matched normal bladder and tumor samples. Knockdown by RNA interference of either p38β or ILK disrupts serum-induced, Rac1-dependent migration and actin cytoskeletal organization in bladder cancer cells. Surprisingly, ILK knockdown causes the selective reduction in p38β cellular protein level, without inhibiting p38β messenger RNA (mRNA) expression. The loss of p38β protein in ILK-depleted cells is partially rescued by the 26S proteasomal inhibitor MG132. Using co-precipitation and bimolecular fluorescent complementation assays, we find that ILK selectively forms cytoplasmic complexes with p38β. In situ proximity ligation assays further demonstrate that serum-stimulated assembly of endogenous ILK–p38β complexes is sensitive to QLT-0267, a small molecule ILK kinase inhibitor. Finally, inhibition of ILK reduces the amplitude and period of serum-induced activation of heat shock protein 27 (Hsp27), a target of p38β implicated in actin cytoskeletal reorganization. Our work identifies Hsp27 as a novel target of ILK–p38β signaling complexes, playing a key role in bladder cancer cell migration.