Prostate cancer biomarkers and the emerging proteomic techniques used in biomarker research

Prostate cancer (CaP) is the second leading cause of cancer-related deaths in North American males and the most common newly diagnosed cancer in men world wide. Biomarkers are widely used for both early detection and prognostic tests for cancer. The current, commonly used biomarker for CaP is serum prostate specific antigen (PSA). However, the specificity of this biomarker is low as its serum level is not only increased in CaP but also in various other diseases, with age and even body mass index. Human body fluids provide an excellent resource for the discovery of biomarkers, with the advantage over tissue/biopsy samples of their ease of access, due to the less invasive nature of collection. However, their analysis presents challenges in terms of variability and validation. Blood and urine are two human body fluids commonly used for CaP research, but their proteomic analyses are limited both by the large dynamic range of protein abundance making detection of low abundance proteins difficult and in the case of urine, by the high salt concentration. To overcome these challenges, different techniques for removal of high abundance proteins and enrichment of low abundance proteins are used. Their applications and limitations are discussed in this review. A number of innovative proteomic techniques have improved detection of biomarkers. They include two dimensional differential gel electrophoresis (2D-DIGE), quantitative mass spectrometry (MS) and functional proteomic studies, i.e., investigating the association of post translational modifications (PTMs) such as phosphorylation, glycosylation and protein degradation. The recent development of quantitative MS techniques such as stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantitation (iTRAQ) and multiple reaction monitoring (MRM) have allowed proteomic researchers to quantitatively compare data from different samples. 2D-DIGE has greatly improved the statistical power of classical 2D gel analysis by introducing an internal control. This chapter aims to review novel CaP biomarkers as well as to discuss current trends in biomarker research from two angles: the source of biomarkers (particularly human body fluids such as blood and urine), and emerging proteomic approaches for biomarker research.

Plant-made therapeutics: An emerging platform in South Africa

The field of plant-made therapeutics in South Africa is well established in the form of exploitation of the country's considerable natural plant diversity, both in the use of native plants in traditional herbal medicines over many centuries, and in the more modern extraction of pharmacologically-active compounds from plants, including those known to traditional healers. In recent years, this has been added to by the use of plants for the stable or transient expression of pharmaceutically-important compounds, largely protein-based biologics and vaccines. South Africa has a well-developed plant biotechnology community, as well as a comprehensive legislative framework for the regulation of the exploitation of local botanic resources, and of genetically-modified organisms. The review explores the investigation of both conventional and recombinant plants for pharmaceutical use in South Africa, as well as describing the relevant legislative and regulatory frameworks. Potential opportunities for national projects, as well as factors limiting biopharming in South Africa are discussed. © 2011.

Viable chimaeric viruses confirm the biological importance of sequence specific maize streak virus movement protein and coat protein interactions

Background. A variety of interactions between up to three different movement proteins (MPs), the coat protein (CP) and genomic DNA mediate the inter- and intra-cellular movement of geminiviruses in the genus Begomovirus. Although movement of viruses in the genus Mastrevirus is less well characterized, direct interactions between a single MP and the CP of these viruses is also clearly involved in both intra- and intercellular trafficking of virus genomic DNA. However, it is currently unknown how specific these MP-CP interactions are, nor how disruption of these interactions might impact on virus viability. Results. Using chimaeric genomes of two strains of Maize streak virus (MSV) we adopted a genetic approach to investigate the gross biological effects of interfering with interactions between virus MP and CP homologues derived from genetically distinct MSV isolates. MP and CP genes were reciprocally exchanged, individually and in pairs, between maize (MSV-Kom)- and Setaria sp. (MSV-Set)-adapted isolates sharing 78% genome-wide sequence identity. All chimaeras were infectious in Zea mays c.v. Jubilee and were characterized in terms of symptomatology and infection efficiency. Compared with their parental viruses, all the chimaeras were attenuated in symptom severity, infection efficiency, and the rate at which symptoms appeared. The exchange of individual MP and CP genes resulted in lower infection efficiency and reduced symptom severity in comparison with exchanges of matched MP-CP pairs. Conclusion. Specific interactions between the mastrevirus MP and CP genes themselves and/or their expression products are important determinants of infection efficiency, rate of symptom development and symptom severity. © 2008 van der Walt et al; licensee BioMed Central Ltd.

Maize streak virus: An old and complex 'emerging' pathogen

Maize streak virus (MSV; Genus Mastrevirus, Family Geminiviridae) occurs throughout Africa, where it causes what is probably the most serious viral crop disease on the continent. It is obligately transmitted by as many as six leafhopper species in the Genus Cicadulina, but mainly by C. mbila Naudé and C. storeyi. In addition to maize, it can infect over 80 other species in the Family Poaceae. Whereas 11 strains of MSV are currently known, only the MSV-A strain is known to cause economically significant streak disease in maize. Severe maize streak disease (MSD) manifests as pronounced, continuous parallel chlorotic streaks on leaves, with severe stunting of the affected plant and, usuallly, a failure to produce complete cobs or seed. Natural resistance to MSV in maize, and/or maize infections caused by non-maize-adapted MSV strains, can result in narrow, interrupted streaks and no obvious yield losses. MSV epidemiology is primarily governed by environmental influences on its vector species, resulting in erratic epidemics every 3-10 years. Even in epidemic years, disease incidences can vary from a few infected plants per field, with little associated yield loss, to 100% infection rates and complete yield loss. Taxonomy: The only virus species known to cause MSD is MSV, the type member of the Genus Mastrevirus in the Family Geminiviridae. In addition to the MSV-A strain, which causes the most severe form of streak disease in maize, 10 other MSV strains (MSV-B to MSV-K) are known to infect barley, wheat, oats, rye, sugarcane, millet and many wild, mostly annual, grass species. Seven other mastrevirus species, many with host and geographical ranges partially overlapping those of MSV, appear to infect primarily perennial grasses. Physical properties: MSV and all related grass mastreviruses have single-component, circular, single-stranded DNA genomes of approximately 2700 bases, encapsidated in 22 × 38-nm geminate particles comprising two incomplete T = 1 icosahedra, with 22 pentameric capsomers composed of a single 32-kDa capsid protein. Particles are generally stable in buffers of pH 4-8. Disease symptoms: In infected maize plants, streak disease initially manifests as minute, pale, circular spots on the lowest exposed portion of the youngest leaves. The only leaves that develop symptoms are those formed after infection, with older leaves remaining healthy. As the disease progresses, newer leaves emerge containing streaks up to several millimetres in length along the leaf veins, with primary veins being less affected than secondary or tertiary veins. The streaks are often fused laterally, appearing as narrow, broken, chlorotic stripes, which may extend over the entire length of severely affected leaves. Lesion colour generally varies from white to yellow, with some virus strains causing red pigmentation on maize leaves and abnormal shoot and flower bunching in grasses. Reduced photosynthesis and increased respiration usually lead to a reduction in leaf length and plant height; thus, maize plants infected at an early stage become severely stunted, producing undersized, misshapen cobs or giving no yield at all. Yield loss in susceptible maize is directly related to the time of infection: Infected seedlings produce no yield or are killed, whereas plants infected at later times are proportionately less affected. Disease control: Disease avoidance can be practised by only planting maize during the early season when viral inoculum loads are lowest. Leafhopper vectors can also be controlled with insecticides such as carbofuran. However, the development and use of streak-resistant cultivars is probably the most effective and economically viable means of preventing streak epidemics. Naturally occurring tolerance to MSV (meaning that, although plants become systemically infected, they do not suffer serious yield losses) has been found, which has primarily been attributed to a single gene, msv-1. However, other MSV resistance genes also exist and improved resistance has been achieved by concentrating these within individual maiz genotypes. Whereas true MSV immunity (meaning that plants cannot be symptomatically infected by the virus) has been achieved in lines that include multiple small-effect resistance genes together with msv-1, it has proven difficult to transfer this immunity into commercial maize genotypes. An alternative resistance strategy using genetic engineering is currently being investigated in South Africa. Useful websites: 〈http://www.mcb.uct.ac.za/MSV/mastrevirus.htm〉; 〈http://www. danforthcenter.org/iltab/geminiviridae/geminiaccess/mastrevirus/Mastrevirus. htm〉. © 2009 Blackwell Publishing Ltd.

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.

Emerging work practice with a telehealth stethoscope

We investigated the collaboration of ten doctor-nurse pairs with a prototype digital telehealth stethoscope. Doctors could see and hear the patient but could not touch them or the stethoscope. The nurse in each pair controlled the stethoscope. For ethical reasons, an experimenter stood in for a patient. Each of the ten interactions was video recorded and analysed to understand the interaction and collaboration between the doctor and nurse. The video recordings were coded and transformed into maps of interaction that were analysed for patterns of activity. The analysis showed that as doctors and nurses became more experienced at using the telehealth stethoscope their collaboration was more effective. The main measure of effectiveness was the number of corrections in stethoscope placement required by the doctor. In early collaborations, the doctors gave many corrections. After several trials, each doctor and nurse had reduced corrections and all pairs reduced their corrections. The significance of this research is the identification of the qualities of effective collaboration in the use of the telehealth stethoscope and telehealth systems more generally.

Creating fashion professionals for the 21st century : a tale of pedagogical tensions and emerging challenges

The ‘Fashion Tales’ Conference identifies three fashion discourses: that of making, that of media, and that of scholarship. We propose a fourth, which provides a foundational base for the others: the discourse of fashion pedagogy. We begin with the argument that to thrive in any of these discourses, all fashion graduates require the ability to navigate the complexities of the 21st century fashion industry. Fashion graduates emerge into a professional world which demands a range of high level capabilities above and beyond those traditionally acknowledged by the discipline. Professional education in fashion must transform itself to accommodate these imperatives. In this paper, we document a tale of fashion learning, teaching and scholarship – the tale of a highly successful future-orientated boutique university-based undergraduate fashion course in Queensland, Australia. The Discipline consistently maintains the highest student satisfaction and lowest attrition of any course in the university, achieves extremely competitive student satisfaction scores when compared with other courses nationally and internationally, and reports outstanding graduate employment outcomes. The core of the article addresses how the course effectively balances five key pedagogical tensions identified from the findings of in-depth focus groups with graduating students, and interviews with teaching staff. The pedagogical tensions are: high concept/ authenticity; high disciplinarity/ interdisciplinarity; high rigour/ play; high autonomy/ scaffolding; and high individuality/ community, where community can be further divided into high challenge and high support. We discuss each of these tensions and how they are characterised within the course, using rich descriptions given by the students. We also draw upon the wider andragogical and learning futures literatures to link the tensions with what is already known about excellence in 21st century higher and further education curriculum and pedagogic practice. We ask: as the fashion industry becomes truly globalised, virtualised, and diversified, and as initial professional training for the industry becomes increasingly massified and performatised, what are the best teaching approaches to produce autonomous, professionally capable, enterprising and responsible graduates into the future? Can the pedagogical balances described in this case study be maintained in the light of these powerful external forces, and if so, how?

The emerging framework of cross-border insolvency in and around Australia : Saad Investments, Japan Airlines and Lehman Brothers – part one

Recent decades have witnessed a global acceleration of legislative and private sector initiatives to deal with Cross-Border insolvency. Legislative institutions include the various national implementations of the Model Law on Cross-Border Insolvency (Model Law) published by the United Nations Commission on International Trade (UNCITRAL).3 Private mechanisms include Cross-Border protocols developed and utilised by insolvency professionals and their advisers (often with the imprimatur of the judiciary), on both general and ad hoc bases. The Asia Pacific region has not escaped the effect of those developments, and the economic turmoil of the past few years has provided an early test for some of the emerging initiatives in that region. This two-part article explores the operation of those institutions through the medium of three recent cases.

The emerging framework of cross-border insolvency in and around Australia : Saad Investments, Japan Airlines and Lehman Brothers – Part Two

Recent decades have witnessed a global acceleration of legislative and private sector initiatives to deal with Cross-Border insolvency. Legislative institutions include the various national implementations of the Model Law on Cross-Border Insolvency (Model Law) published by the United Nations Commission on International Trade (UNCITRAL).3 Private mechanisms include Cross-Border protocols developed and utilised by insolvency professionals and their advisers (often with the imprimatur of the judiciary), on both general and ad hoc bases. The Asia Pacific region has not escaped the effect of those developments, and the economic turmoil of the past few years has provided an early test for some of the emerging initiatives in that region. This two-part article explores the operation of those institutions through the medium of three recent cases.

Emerging from student to practitioner : a cumulative development tool for students

PURPOSE: This pilot project’s aim was to trial a tool and process for developing students’ ability to engage in self-assessment using reflection on their clinical experiences, including feedback from workplace learning, in order to aid them in linking theory to practice and develop strategies to improve performance. BACKGROUND: In nursing education, students can experience a mismatch in performance compared to theoretical learning, this is referred to as the ‘theory practice gap’ (Scully 2011, Chan Chan & Liu 2011). One specific contributing factor seems to be students’ inability to engage in meaningful reflection and self-correcting behaviours. A self-assessment strategy was implemented within a third year clinical unit to ameliorate this mismatch with encouraging results, as students developed self-direction in addressing learning needs. In this pilot project the above strategy was adapted for implementation between different clinical units, to create a whole of course approach to integrating workplace learning. METHOD: The methodology underpinning this project is a scaffolded, supported reflective practice process. Improved self-assessment skills is achieved by students reflecting on and engaging with feedback, then mapping this to learning outcomes to identify where performance can be improved. Evaluation of this project includes: collation of student feedback identifying successful strategies along with barriers encountered in implementation; feedback from students and teachers via above processes and tools; and comparison of the number of learning contracts issued in clinical nursing units with similar cohorts. RESULTS: Results will be complete by May 2012 and include analysis of the data collected via the above evaluation methods. Other outcomes will include the refined process and tool, plus resources that should improve cost effectiveness without reducing student support. CONCLUSION: Implementing these tools and processes over the entire student’s learning package, will assist them to demonstrate progressive development through the course. Students will have learnt to understand feedback and integrate these skills for life-long learning.

Modeling destination brand equity in an emerging long haul market

The destination branding literature emerged as recently as 1998, and there remains a dearth of empirical data that tests the effectiveness of brand campaigns over time. This paper reports the results of an investigation into consumer-based brand equity for Australia as a long haul destination in an emerging South American market. In spite of the high level of academic interest in the measurement of perceptions of destinations since the 1970s, few previous studies have examined perceptions held by South American consumers. Findings suggest that destination brand awareness, brand image, and brand value are positively related to brand loyalty for a long-haul destination. The results also indicate that Australia is a more compelling destination brand for previous visitors compared to non-visitors.

Ingenious : Emerging Youth Cultures in Urban Australia

The book documents new findings on the contribution of migrant young people to Australia’s urban life. The essays collected traces teenagers within a world of city suburbs and P plates, shopping malls and chat rooms and text messages. Proud of their migrant backgrounds, they are moving away from explicit ethnically defined cultural groups to focus on their place in contemporary Australian society. These young people through their every day activities are redefining what it means to be an Australian The book is edited by widely published cultural researchers Melissa Butcher from the University of Sydney and Mandy Thomas from the Australian National University who together worked on the GENERATE project. It is far too common for our youth to be portrayed as not belonging to our dominant or mainstream culture. In Ingenious, the editors study the kaleidoscope of influences and environments our youth move within - online networks, dance parties and more - to paint a flexible, innovative generation.

The emerging role of the Board of Directors in enterprise business technology governance

In an increasingly business technology (BT) dependent world, the impact of the extraordinary changes brought about by the nexus of mobile and cloud technologies, social media and big data is increasingly being felt in the board room. As leaders of enterprises of every type and size, board directors can no longer afford to ignore, delegate or avoid BT-related decisions. Competitive, financial and reputational risk is increased if boards fail to recognize their role in governing technology as an asset and in removing barriers to improving enterprise business technology governance (EBTG). Directors’ awareness of the need for EBTG is increasing. However, industry research shows that board level willingness to rectify the gap between awareness and action is very low or non-existent. This literature review-based research identifies barriers to EBTG effectiveness. It provides a practical starting point for board analysis. We offer four outcomes that boards might focus on to ensure the organizations they govern are not left behind by those led by the upcoming new breed of technology-savvy leaders. Most extant research looks backward for examples, examining data pre-2010, the time when a tipping point in the personal and business use of multimedia and mobile-internet devices significantly deepened the impacts of the identified nexus technology forces, and began rapidly changing the way many businesses engage with their customers, employees and stakeholders. We situate our work amidst these nexus forces, discuss the board’s role in EBTG in this context, and modernize current definitions of enterprise technology governance. The primary limitation faced is the lack of scholarly research relating to EBTG in the rapidly changing digital economy. Although we have used recent (2011 - 2013) industry surveys, the volume of these surveys and congruence across them is significant in terms of levels of increased awareness and calls for increased board attention and competency in EBTG and strategic information use. Where possible we have used scholarly research to illustrate or discuss industry findings.