The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

The role of mindfulness in an extended TPB framework to understand drivers’ speeding intentions in school zones.

Many researchers have demonstrated the applicability of the Theory of Planned Behaviour (TPB) in predicting both intention to speed and actual speeding behaviour. However, there remain shortcomings in the explanatory power of the TPB, with research suggesting that even when drivers had reported an intention to not speed approximately 25% of drivers report behaviour that does not align with their intentions (i.e., they engaged in speeding, Elliott & Armitage, 2006). This research explores the role of a novel and promising construct, mindfulness, in enhancing the explanatory utility of the TPB for the understanding of drivers’ speeding behaviour in school zones. Mindfulness is a concept which has been widely used in studies of consciousness, but has recently been applied to the understanding of behaviour in other areas, including clinical psychology, physical activity, education and business. It has been suggested that mindfulness can also be applied to road safety, though its application within this context currently remains limited. This study was based on an e-survey of the general driving public (N=240). Overall, the results identified mindfulness as a construct which may aid understanding of the relationship between drivers’ intentions and behaviour. Theoretically, the findings may have implications in terms of identifying mindfulness as an additional explanatory construct within a TPB framework. In road safety practice, the findings suggest that efficacious countermeasures around school zones may be those that function to heighten drivers’ mindfulness, such as flashing lights and physical speed reduction measures.

Interpersonal coupling in rowing : the mediating role of the environment

Evidence currently supports the view that intentional interpersonal coordination (IIC) is a self-organizing phenomenon facilitated by visual perception of co-actors in a coordinative coupling (Schmidt, Richardson, Arsenault, & Galantucci, 2007). The present study examines how apparent IIC is achieved in situations where visual information is limited for co-actors in a rowing boat. In paired rowing boats only one of the actors, [bow seat] gets to see the actions of the other [stroke seat]. Thus IIC appears to be facilitated despite the lack of important visual information for the control of the dyad. Adopting a mimetic approach to expert coordination, the present study qualitatively examined the experiences of expert performers (N=9) and coaches (N=4) with respect to how IIC was achieved in paired rowing boats. Themes were explored using inductive content analysis, which led to layered model of control. Rowers and coaches reported the use of multiple perceptual sources in order to achieve IIC. As expected(Kelso, 1995; Schmidt & O’Brien, 1997; Turvey, 1990), rowers in the bow of a pair boat make use of visual information provided by the partner in front of them [stroke]. However, this perceptual information is subordinate to perception Motor Learning and Control S111 of the relationship between the boat hull and water passing beside it. Stroke seat, in the absence of visual information about his/her partner, achieves coordination by picking up information about the lifting or looming of the boat’s stern along with water passage past the hull. In this case it appears that apparent or desired IIC is supported by the perception of extra-personal variables, in this case boat behavior; as this perceptual information source is used by both actors. To conclude, co-actors in two person rowing boats use multiple sources of perceptual information for apparent IIC that changes according to task constraints. Where visual information is restricted IIC is facilitated via extra-personal perceptual information and apparent IIC switches to intentional extra-personal coordination.

New and young firms Entrepreneurship policy and the role of government – evidence from the Federation of Small Businesses survey

Purpose – The purpose of this paper is to investigate whether new and young firms are different from older firms. This analysis is undertaken to explore general characteristics, use of external resources and growth orientation. Design/methodology/approach – Data from the 2008 UK Federation of Small Businesses survey provided 8,000 responses. Quantitative analysis identified significantly different characteristics of firms from 0-4, 4-9, 9-19 and 20+ years. Factor analysis was utilised to identify the advice sets, finance and public procurement customers of greatest interest, with ANOVA used to statistically compare firms in the identified age groups with different growth aspirations. Findings – The findings reveal key differences between new, young and older firms in terms of characteristics including business sector, owner/manager age, education/business experience, legal status, intellectual property and trading performance. New and young firms were more able to access beneficial resources in terms of finance and advice from several sources. New and young firms were also able to more easily access government and external finance, as well as government advice, but less able to access public procurement. Research limitations/implications – New and young firms are utilising external networks to access several resources for development purposes, and this differs for older firms. This suggests that a more explicit age-differentiated focus is required for government policies aimed at supporting firm growth. Originality/value – The study provides important baseline data for future quantitative and qualitative studies focused on the impact of firm age and government policy.

The ancient gene C12orf29 : an exploration of its role in the chordate body plan

The sheep (Ovis aries) is commonly used as a large animal model in skeletal research. Although the sheep genome has been sequenced there are still only a limited number of annotated mRNA sequences in public databases. A complementary DNA (cDNA) library was constructed to provide a generic resource for further exploration of genes that are actively expressed in bone cells in sheep. It was anticipated that the cDNA library would provide molecular tools for further research into the process of fracture repair and bone homeostasis, and add to the existing body of knowledge. One of the hallmarks of cDNA libraries has been the identification of novel genes and in this library the full open reading frame of the gene C12orf29 was cloned and characterised. This gene codes for a protein of unknown function with a molecular weight of 37 kDa. A literature search showed that no previous studies had been conducted into the biological role of C12orf29, except for some bioinformatics studies that suggested a possible link with cancer. Phylogenetic analyses revealed that C12orf29 had an ancient pedigree with a homologous gene found in some bacterial taxa. This implied that the gene was present in the last common eukaryotic ancestor, thought to have existed more than 2 billion years ago. This notion was further supported by the fact that the gene is found in taxa belonging to the two major eukaryotic branches, bikonts and unikonts. In the bikont supergroup a C12orf29-like gene was found in the single celled protist Naegleria gruberi, whereas in the unikont supergroup, encompassing the metazoa, the gene is universal to all chordate and, therefore, vertebrate species. It appears to have been lost to the majority of cnidaria and protostomes taxa; however, C12orf29-like genes have been found in the cnidarian freshwater hydra and the protostome Pacific oyster. The experimental data indicate that C12orf29 has a structural role in skeletal development and tissue homeostasis, whereas in silico analysis of the human C12orf29 promoter region suggests that its expression is potentially under the control of the NOTCH, WNT and TGF- developmental pathways, as well SOX9 and BAPX1; pathways that are all heavily involved in skeletogenesis. Taken together, this investigation provides strong evidence that C12orf29 has a very important role in the chordate body plan, in early skeletal development, cartilage homeostasis, and also a possible link with spina bifida in humans.

The role of EBV-encoded microRNAs in B cell differentiation

Epstein Barr virus (EBV) is a common γ-herpes virus, infecting approximately 90% of the world‟s population. It is also one of the first known viruses known to be oncogenic, and is associated with a number of tumour types, primarily lymphomas. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and many human miRNAs have been associated with the development of malignancies including cancer. EBV was the first human virus identified to express miRNAs and encodes more than 40 miRNAs within its genome. Yet, an understanding of the targets of EBV-miRNAs, and thereby the function of them in pathogenesis remains sadly limited. This study identifies a potential novel target of EBV-miRNAs, MECP2 and characterises the miRNA:mRNA interactions between two previously identified novel targets; Bim and EBF1. In particular, this study focuses upon the interaction between EBF1 and the EBV-miRNA BART11-5p, demonstrating a 151bp region of the EBF1 3‟UTR that is capable of mediating the silencing of luciferase expression by BART11-5p but is not capable of silencing a full length EBF1-3‟UTR luciferase construct. This study provides evidence that EBF1 may be a target of one or more EBV-miRNAs.

The journey of the role of religious faith in corrections : the case of circles of support and accountability

A renewal of interest has occurred in the relationship between religion, penal policy, and systems of criminal justice in different countries. This has been manifested in the development of religious programmes in prison and community settings. The subject has also precipitated a substantial body of empirical research, in addition to theorising the impacts of religion upon offending behaviour. However, specific faith‐based measures have attracted limited attention, mainly because of the empirical complexity of measuring the relationship between faith and behavioural change. These issues are addressed in this article by considering the recentlyemerged practice of Circles of Support and Accountability (COSA).

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise.

Consultant engagement for computer system selection: a pro-active client role in small enterprises

Because of their limited number of senior positions and fewer alternative career paths, small businesses have a more difficult time attracting and retaining skilled information systems (IS) staff and are thus dependent upon external expertise. Small businesses are particularly dependent on outside expertise when first computerizing. Because small businesses suffer from severe financial constraints. it is often difficult to justify the cost of custom software. Hence. for many small businesses, engaging a consultant to help with identifying suitable packaged software and related hardware, is their first critical step toward computerization. This study explores the importance of proactive client involvement when engaging a consultant to assist with computer system selection in small businesses. Client involvement throughout consultant engagement is found to be integral to project success and frequently lacking due to misconceptions of small businesses regarding their role. Small businesses often overestimate the impact of consultant and vendor support in achieving successful computer system selection and implementation. For consultant engagement to be successful, the process must be viewed as being directed toward the achievement of specific organizational results where the client accepts responsibility for direction of the process.

Becoming a pharmacist : the role of curriculum in professional identity formation

Objective To understand how the formal curriculum experience of an Australian undergraduate pharmacy program supports students’ professional identity formation. Methods A qualitative ethnographic study was conducted over four weeks using participant observation and examined the ‘typical’ student experience from the perspective of a pharmacist. A one-week period of observation was undertaken with each of the four year groups (that is, for years one to four) comprising the undergraduate curriculum. Data were collected through observation of the formal curriculum experience using field notes, a reflective journal and informal interviews with 38 pharmacy students. Data were analyzed thematically using an a priori analytical framework. Results Our findings showed that the observed curriculum was a conventional curricular experience which focused on the provision of technical knowledge and provided some opportunities for practical engagement. There were some opportunities for students to imagine themselves as pharmacists, for example, when the lecture content related to practice or teaching staff described their approach to practice problems. However, there were limited opportunities for students to observe pharmacist role models, experiment with being a pharmacist or evaluate their professional identities. While curricular learning activities were available for students to develop as pharmacists e.g. patient counseling, there was no contact with patients and pharmacist academic staff tended to role model as educators with little evidence of their pharmacist selves. Conclusion These findings suggest that the current conventional approach to the curriculum design may not be fully enabling learning experiences which support students in successfully negotiating their professional identities. Instead it appeared to reinforce their identities as students with a naïve understanding of professional practice, making their future transition to professional practice challenging.

Role of amine oxidase expression to maintain putrescine homeostasis in Rhodococcus opacus

While applications of amine oxidases are increasing, few have been characterised and our understanding of their biological role and strategies for bacteria exploitation are limited. By altering the nitrogen source (NH4Cl, putrescine and cadaverine (diamines) and butylamine (monoamine)) and concentration, we have identified a constitutive flavin dependent oxidase (EC 1.4.3.10) within Rhodococcus opacus. The activity of this oxidase can be increased by over two orders of magnitude in the presence of aliphatic diamines. In addition, the expression of a copper dependent diamine oxidase (EC 1.4.3.22) was observed at diamine concentrations>1mM or when cells were grown with butylamine, which acts to inhibit the flavin oxidase. A Michaelis-Menten kinetic treatment of the flavin oxidase delivered a Michaelis constant (KM)=190μM and maximum rate (kcat)=21.8s(-1) for the oxidative deamination of putrescine with a lower KM (=60μM) and comparable kcat (=18.2s(-1)) for the copper oxidase. MALDI-TOF and genomic analyses have indicated a metabolic clustering of functionally related genes. From a consideration of amine oxidase specificity and sequence homology, we propose a putrescine degradation pathway within Rhodococcus that utilises oxidases in tandem with subsequent dehydrogenase and transaminase enzymes. The implications of PUT homeostasis through the action of the two oxidases are discussed with respect to stressors, evolution and application in microbe-assisted phytoremediation or bio-augmentation.

The global public health issue of pharmaceutical waste : what role for pharmacists?

Purpose Pharmaceuticals have played an important role in improving the quality of life of the human population in modern times. However, it must also be acknowledged that both the production and use of pharmaceuticals have a significant, negative impact on the environment and consequently, a negative impact on the health of humans and wildlife. This negative impact is due to the embedded carbon in pharmaceuticals' manufacture and distribution and the waste generated in their manufacture, consumption and disposal. Pharmaceutical waste is comprised of contaminated waste (unwanted pharmaceuticals and their original containers) and non-contaminated waste (non-hazardous packaging waste). The paper aims to discuss these issues. Design/methodology/approach The article is a literature review. Findings The article identified a gap in the literature around pharmacist attitudes and behaviour toward the environmentally responsible handling of pharmaceutical waste. Originality/value Pharmacists, with their professional commitment to the quality use of medicines and their active participation in the medicines management pathway, already play an important role in the more sustainable use of pharmaceuticals. Even so, they have the potential to play an even greater role with the environmentally responsible disposal of pharmaceutical waste (including packaging waste) and the education of other health professionals and the general public on this topic.

Freedom to choose? Embryo selection, reproductive decision-making and the role of the state

Involving the biopsy of an eight-cell embryo, PGD has been hailed as a means of making reproductive decisions without having to face the heart-wrenching decision to abort an affected foetus. However, controversy around the kinds of traits for which testing can be done, and who has access to the technology, has led to questions about the way in which the technology is developing. Women who are allowed to access in vitro fertilisation (IVF) services can currently also access PGD in limited circumstances.

Designing and evaluating an online role play in conflict management

Purpose This paper aims to identify, through a literature review, key issues regarding how online role plays can be designed and to apply them when designing a role play on conflict management. Design/methodology/approach By drawing on the key issues identified in the literature review, a role play on conflict management was designed and evaluated. Data were collected by developing a survey that focused on perceived learning, participation and satisfaction. Findings Overall, a majority of the students felt that they learned and participated in the role play. The most positive finding was that the students were satisfied with their role play experience. Research limitations/implications Researchers are urged to further develop the dimensions and measures of online role play success. The measures that were developed for evaluating perceived learning, participation and satisfaction with role plays can be further developed and tested. It is suggested that the effects on learning need to be further explored. Practical implications It is suggested that teachers take the identified key issues of online role play design into account. An important challenge seems to be to encourage students to reflect and do additional reading and research in relation with online role plays. Originality/value Online collaboration is commonly argued as beneficial from an e-learning perspective. However, a challenge for research and practice is to learn how collaborative e-learning activities may be developed. This paper contributes by focusing on how online role plays can be designed and evaluated.