Colour and Camp Bring Shakespeare’s As You Like It to Life

As You Like It By Shakespeare. La Boite Theatre Company, Brisbane, February 24. DURING the past three years, La Boite Theatre Company has started each season with a modern adaptation of a Shakespearean favourite. This time, director David Bertold's choice is not a tragedy but As You Like It, a comedy about love's twists and turns in which a strong female figure, Rosalind, takes the leading role...

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.

Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology

Tumour necrosis factor (TNF) is a pleiotropic cytokine with dual roles in cancer biology including prostate cancer (PCa). On the one hand, there is evidence that it stimulates tumour angiogenesis, is involved in the initiation of PCa from an androgen-dependent to a castrate resistant state, plays a role in epithelial to mesenchymal plasiticity, and may contribute to the aberrant regulation of eicosanoid pathways. On the other hand, TNF has also been reported to inhibit neovascularisation, induce apoptosis of PCa cells, and stimulate anti-tumour immunity. Much of the confusion surrounding its seemingly paradoxical roles in cancer biology stems from the dependence of its effects on the biological model within which TNF is investigated. This review will address some of these issues, and also discuss on the therapeutic implications.

Scaffolds for growth factor delivery as applied to bone tissue engineering

There remains a substantial shortfall in treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient, has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors; which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However cost and potential complications associated with growth factors means controlled release is an important consideration in the design of new bone tissue engineering strategies. This review will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

Fatalism, superstition, religion, and culture : road user beliefs and behaviour in Pakistan

Road traffic crashes have emerged as a major health problem around the world. Road crash fatalities and injuries have been reduced significantly in developed countries, but they are still an issue in low and middle-income countries. The World Health Organization (WHO, 2009) estimates that the death toll from road crashes in low- and middle-income nations is more than 1 million people per year, or about 90% of the global road toll, even though these countries only account for 48% of the world's vehicles. Furthermore, it is estimated that approximately 265,000 people die every year in road crashes in South Asian countries and Pakistan stands out with 41,494 approximately deaths per year. Pakistan has the highest rate of fatalities per 100,000 population in the region and its road crash fatality rate of 25.3 per 100,000 population is more than three times that of Australia's. High numbers of road crashes not only cause pain and suffering to the population at large, but are also a serious drain on the country's economy, which Pakistan can ill-afford. Most studies identify human factors as the main set of contributing factors to road crashes, well ahead of road environment and vehicle factors. In developing countries especially, attention and resources are required in order to improve things such as vehicle roadworthiness and poor road infrastructure. However, attention to human factors is also critical. Human factors which contribute to crashes include high risk behaviours like speeding and drink driving, and neglect of protective behaviours such as helmet wearing and seat belt wearing. Much research has been devoted to the attitudes, beliefs and perceptions which contribute to these behaviours and omissions, in order to develop interventions aimed at increasing safer road use behaviours and thereby reducing crashes. However, less progress has been made in addressing human factors contributing to crashes in developing countries as compared to the many improvements in road environments and vehicle standards, and this is especially true of fatalistic beliefs and behaviours. This is a significant omission, since in different cultures in developing countries there are strong worldviews in which predestination persists as a central idea, i.e. that one's life (and death) and other events have been mapped out and are predetermined. Fatalism refers to a particular way in which people regard the events that occur in their lives, usually expressed as a belief that an individual does not have personal control over circumstances and that their lives are determined through a divine or powerful external agency (Hazen & Ehiri, 2006). These views are at odds with the dominant themes of modern health promotion movements, and present significant challenges for health advocates who aim to avert road crashes and diminish their consequences. The limited literature on fatalism reveals that it is not a simple concept, with religion, culture, superstition, experience, education and degree of perceived control of one's life all being implicated in accounts of fatalism. One distinction in the literature that seems promising is the distinction between empirical and theological fatalism, although there are areas of uncertainty about how well-defined the distinction between these types of fatalism is. Research into road safety in Pakistan is scarce, as is the case for other South Asian countries. From the review of the literature conducted, it is clear that the descriptions given of the different belief systems in developing countries including Pakistan are not entirely helpful for health promotion purposes and that further research is warranted on the influence of fatalism, superstition and other related beliefs in road safety. Based on the information available, a conceptual framework is developed as a means of structuring and focusing the research and analysis. The framework is focused on the influence of fatalism, superstition, religion and culture on beliefs about crashes and road user behaviour. Accordingly, this research aims to provide an understanding of the operation of fatalism and related beliefs in Pakistan to assist in the development and implementation of effective and culturally appropriate interventions. The research examines the influence of fatalism, superstition, religious and cultural beliefs on risky road use in Pakistan and is guided by three research questions: 1. What are the perceptions of road crash causation in Pakistan, in particular the role of fatalism, superstition, religious and cultural beliefs? 2. How does fatalism, superstition, and religious and cultural beliefs influence road user behaviour in Pakistan? 3. Do fatalism, superstition, and religious and cultural beliefs work as obstacles to road safety interventions in Pakistan? To address these questions, a qualitative research methodology was developed. The research focused on gathering data through individual in-depth interviewing using a semi-structured interview format. A sample of 30 participants was interviewed in Pakistan in the cities of Lahore, Rawalpindi and Islamabad. The participants included policy makers (with responsibility for traffic law), experienced police officers, religious orators, professional drivers (truck, bus and taxi) and general drivers selected through a combination of purposive, criterion and snowball sampling. The transcripts were translated from Urdu and analysed using a thematic analysis approach guided by the conceptual framework. The findings were divided into four areas: attribution of crash causation to fatalism; attribution of road crashes to beliefs about superstition and malicious acts; beliefs about road crash causation linked to popular concepts of religion; and implications for behaviour, safety and enforcement. Fatalism was almost universally evident, and expressed in a number of ways. Fate was used to rationalise fatal crashes using the argument that the people killed were destined to die that day, one way or another. Related to this was the sense of either not being fully in control of the vehicle, or not needing to take safety precautions, because crashes were predestined anyway. A variety of superstitious-based crash attributions and coping methods to deal with road crashes were also found, such as belief in the role of the evil eye in contributing to road crashes and the use of black magic by rivals or enemies as a crash cause. There were also beliefs related to popular conceptions of religion, such as the role of crashes as a test of life or a source of martyrdom. However, superstitions did not appear to be an alternative to religious beliefs. Fate appeared as the 'default attribution' for a crash when all other explanations failed to account for the incident. This pervasive belief was utilised to justify risky road use behaviour and to resist messages about preventive measures. There was a strong religious underpinning to the statement of fatalistic beliefs (this reflects popular conceptions of Islam rather than scholarly interpretations), but also an overlap with superstitious and other culturally and religious-based beliefs which have longer-standing roots in Pakistani culture. A particular issue which is explored in more detail is the way in which these beliefs and their interpretation within Pakistani society contributed to poor police reporting of crashes. The pervasive nature of fatalistic beliefs in Pakistan affects road user behaviour by supporting continued risk taking behaviour on the road, and by interfering with public health messages about behaviours which would reduce the risk of traffic crashes. The widespread influence of these beliefs on the ways that people respond to traffic crashes and the death of family members contribute to low crash reporting rates and to a system which appears difficult to change. Fate also appeared to be a major contributing factor to non-reporting of road crashes. There also appeared to be a relationship between police enforcement and (lack of) awareness of road rules. It also appears likely that beliefs can influence police work, especially in the case of road crash investigation and the development of strategies. It is anticipated that the findings could be used as a blueprint for the design of interventions aimed at influencing broad-spectrum health attitudes and practices among the communities where fatalism is prevalent. The findings have also identified aspects of beliefs that have complex social implications when designing and piloting driver intervention strategies. By understanding attitudes and behaviours related to fatalism, superstition and other related concepts, it should be possible to improve the education of general road users, such that they are less likely to attribute road crashes to chance, fate, or superstition. This study also underscores the understanding of this issue in high echelons of society (e.g., policy makers, senior police officers) as their role is vital in dispelling road users' misconceptions about the risks of road crashes. The promotion of an evidence or scientifically-based approach to road user behaviour and road safety is recommended, along with improved professional education for police and policy makers.

The factor structure of the COPE Questionnaire in a sample of clinically depressed and anxious adults

The Coping Orientation to Problems Experienced is a multidimensional scale designed to assess how people respond to stress. The COPE has been validated in a variety of populations displaying variations in factor structure. However, in terms of mental health populations, it has only been validated in alcohol-dependent samples. This paper investigated the factor structure of the COPE in a sample of adults diagnosed with depression and anxiety. Two hundred and seventy-one patients attending cognitive behaviour therapy for anxiety and depression completed the COPE. Confirmatory factor analysis found a poor fit for both lower order and higher order factors based upon the Lyne and Roger (2000) study. Exploratory factor analyses identified six primary subscales (Active Planning, Social Support, Denial, Acceptance, Disengagement, Restraint) which explained approximately 60% of the variance in coping. These 6 subscales may assist researchers and clinicians to validly measure coping in anxious and depressed adults.

Teacher Reporting Attitudes Scale (TRAS): confirmatory and exploratory factor analyses with a Malaysian sample.

The Teacher Reporting Attitude Scale (TRAS) is a newly developed tool to assess teachers’ attitudes toward reporting child abuse and neglect. This article reports on an investigation of the factor structure and psychometric properties of the short form Malay version of the TRAS. A self-report cross-sectional survey was conducted with 667 teachers in 14 randomly selected schools in Selangor state, Malaysia. Analyses were conducted in a 3-stage process using both confirmatory (stages 1 and 3) and exploratory factor analyses (stage 2) to test, modify, and confirm the underlying factor structure of the TRAS in a non-Western teacher sample. Confirmatory factor analysis did not support a 3-factor model previously reported in the original TRAS study. Exploratory factor analysis revealed an 8-item, 4-factor structure. Further confirmatory factor analysis demonstrated appropriateness of the 4-factor structure. Reliability estimates for the four factors—commitment, value, concern, and confidence—were moderate. The modified short form TRAS (Malay version) has potential to be used as a simple tool for relatively quick assessment of teachers’ attitudes toward reporting child abuse and neglect. Cross-cultural differences in attitudes toward reporting may exist and the transferability of newly developed instruments to other populations should be evaluated.

Would you like ice with that?

900-word travel article about Iceland.

FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer

Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.

A confirmatory factor analysis of the Observer Alexithymia Scale in treatment seeking alcohol-dependent patients

Confirmatory factor analyses evaluated the factorial validity of the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample. Observation was conducted by clinical psychologists. All models examined were rejected, given their poor fit. Given the psychometric limitations of the OAS shown in this study, the OAS may not be the most appropriate measure to use early in treatment among alcohol-dependent individuals.

Melt-textured YBa2Cu3O7-x wires having plate-like grains

YBCO wires which consist of well oriented plate-like fine grains are fabricated using a moving furnace to achieve higher mechanical strength. Melt-texturing experiments have been undertaken on YBCO wires with two different compositions: YBa1.5Cu2.9O7-x, and YBa1.8Cu3.0O7-x. Wires are extruded from a mixture of precursor powders (formed by a coprecipitation process) then textured by firing in a moving furnace. Size of secondary phases such as barium cuprate and copper oxide, and overall composition of the sample affect the orientation of the fine grains. At zero magnetic field, the YBa1.5Cu2.9O7-x wire shows the highest critical current density of 1,450 Acm-2 and 8,770 Acm-2 at 77K and 4.2K, respectively. At 1 T, critical current densities of 30 Acm-2 and 200 Acm-2, respectively, are obtained at 77K and 4.2K. Magnetisation curves are also obtained for one sample to evaluate critical current density using the Bean model. Analysis of the microstructure indicates that the starting composition of the green body significantly affects the achievement of grain alignment via melt-texturing processes.

University Student Depression Inventory (USDI) : confirmatory factor analysis and review of psychometric properties

Background: The 30-item USDI is a self-report measure that assesses depressive symptoms among university students. It consists of three correlated three factors: Lethargy, Cognitive-Emotional and Academic motivation. The current research used confirmatory factor analysis to asses construct validity and determine whether the original factor structure would be replicated in a different sample. Psychometric properties were also examined. Method: Participants were 1148 students (mean age 22.84 years, SD = 6.85) across all faculties from a large Australian metropolitan university. Students completed a questionnaire comprising of the USDI, the Depression Anxiety Stress Scale (DASS) and Life Satisfaction Scale (LSS). Results: The three correlated factor model was shown to be an acceptable fit to the data, indicating sound construct validity. Internal consistency of the scale was also demonstrated to be sound, with high Cronbach Alpha values. Temporal stability of the scale was also shown to be strong through test-retest analysis. Finally, concurrent and discriminant validity was examined with correlations between the USDI and DASS subscales as well as the LSS, with sound results contributing to further support the construct validity of the scale. Cut-off points were also developed to aid total score interpretation. Limitations: Response rates are unclear. In addition, the representativeness of the sample could be improved potentially through targeted recruitment (i.e. reviewing the online sample statistics during data collection, examining the representativeness trends and addressing particular faculties within the university that were underrepresented). Conclusions: The USDI provides a valid and reliable method of assessing depressive symptoms found among university students.

Influence of grain boundaries on the vibrational properties of silver nanowires

Metal and semiconductor nanowires (NWs) have been widely employed as the building blocks of the nanoelectromechanical systems, which usually acted a resonant beam. Recent researches reported that nanowires are often polycrystalline, which contains grain boundaries (GBs) that transect the whole nanowire into a bamboo like structure. Based on the larger-scale molecular dynamics (MD) simulations, a comprehensive investigation of the influence from grain boundaries on the vibrational properties of doubly clamped Ag NWs is conducted. It is found that, the presence of grain boundary will result in significant energy dissipation during the resonance of polycrystalline NWs, which leads a great deterioration to the quality factor. Further investigation reveals that the energy dissipation is originated from the plastic deformation of polycrystalline NWs in the form of the nucleation of partial dislocations or the generation of micro stacking faults around the GBs and the micro stacking faults is found to keep almost intact during the whole vibration process. Moreover, it is observed that the closer of the grain boundary getting to the regions with the highest strain state, the more energy dissipation will be resulted from the plastic deformation. In addition, either the increase of the number of grain boundaries or the decrease of the distance between the grain boundary and the highest strain state region is observed to induce a lower first resonance frequency. This work sheds lights on the better understanding of the mechanical properties of polycrystalline NWs, which benefits the increasing utilities of NWs in diverse nano-electronic devices.