Gemcitabine reactivates epigenetically silenced genes and functions as a DNA methyltransferase inhibitor

Gemcitabine is indicated in combination with cisplatin as first-line therapy for solid tumours including non-small cell lung cancer (NSCLC), bladder cancer and mesothelioma. Gemcitabine is an analogue of pyrimidine cytosine and functions as an anti-metabolite. Structurally, however, gemcitabine has similarities to 5-aza-2-deoxycytidine (decitabine/Dacogen®), a DNA methyltransferase inhibitor (DNMTi). NSCLC, mesothelioma and prostate cancer cell lines were treated with decitabine and gemcitabine. Reactivation of epigenetically silenced genes was examined by RT-PCR/qPCR. DNA methyltransferase activity in nuclear extracts and recombinant proteins was measured using a DNA methyltransferase assay, and alterations in DNA methylation status were examined using methylation-specific PCR (MS-PCR) and pyrosequencing. We observe a reactivation of several epigenetically silenced genes including GSTP1, IGFBP3 and RASSF1A. Gemcitabine functionally inhibited DNA methyltransferase activity in both nuclear extracts and recombinant proteins. Gemcitabine dramatically destabilised DNMT1 protein. However, DNA CpG methylation was for the most part unaffected by gemcitabine. In conclusion, gemcitabine both inhibits and destabilises DNA methyltransferases and reactivates epigenetically silenced genes having activity equivalent to decitabine at concentrations significantly lower than those achieved in the treatment of patients with solid tumours. This property may contribute to the anticancer activity of gemcitabine.

Trends in juvenile detention in Australia

This paper provides an overview of key trends in juvenile detention in Australia, based on data contained in the Australian Institute of Criminology’s (AIC’s) Juveniles in Detention in Australia Monitoring Program database and then provides a discussion of two key trends in juvenile detention—the national increase in the proportion of juvenile detainees that is remanded (rather than sentenced) and the increase in the over-representation of Indigenous juveniles in detention.

Comparing outcomes of a school based injury prevention intervention for low-medium risk adolescents with high-risk adoelscents

High-risk adolescents are shown to jeopardise their future social and health functioning as well as placing themselves and others at immediate risk of harm. The challenge of “reaching” high-risk adolescents, who are often marginalised, is considerable. There is a positive relationship between age and risk taking behaviors during adolescence. This study examines outcomes (alcohol use, transport risk behaviors, violence) of a school based intervention (SPIY) by comparing low-medium risk adolescents with high-risk adolescents over a six month period.

Thorough assessment of DNA preservation from fossil bone and sediments excavated from a late Pleistocene–Holocene cave deposit on Kangaroo Island, South Australia

Fossils and sediments preserved in caves are an excellent source of information for investigating impacts of past environmental changes on biodiversity. Until recently studies have relied on morphology-based palaeontological approaches, but recent advances in molecular analytical methods offer excellent potential for extracting a greater array of biological information from these sites. This study presents a thorough assessment of DNA preservation from late Pleistocene–Holocene vertebrate fossils and sediments from Kelly Hill Cave Kangaroo Island, South Australia. Using a combination of extraction techniques and sequencing technologies, ancient DNA was characterised from over 70 bones and 20 sediment samples from 15 stratigraphic layers ranging in age from >20 ka to ∼6.8 ka. A combination of primers targeting marsupial and placental mammals, reptiles and two universal plant primers were used to reveal genetic biodiversity for comparison with the mainland and with the morphological fossil record for Kelly Hill Cave. We demonstrate that Kelly Hill Cave has excellent long-term DNA preservation, back to at least 20 ka. This contrasts with the majority of Australian cave sites thus far explored for ancient DNA preservation, and highlights the great promise Kangaroo Island caves hold for yielding the hitherto-elusive DNA of extinct Australian Pleistocene species.

Would you like data with that? Library provision of financial datasets

Within the QUT Business School (QUTBS)– researchers across economics, finance and accounting depend on data driven research. They analyze historic and global financial data across a range of instruments to understand the relationships and effects between them as they respond to news and events in their region. Scholars and Higher Degree Research Students in turn seek out universities which offer these particular datasets to further their research. This involves downloading and manipulating large datasets, often with a focus on depth of detail, frequency and long tail historical data. This is stock exchange data and has potential commercial value therefore the license for access tends to be very expensive. This poster reports the following findings: •The library has a part to play in freeing up researchers from the burden of negotiating subscriptions, fundraising and managing the legal requirements around license and access. •The role of the library is to communicate the nature and potential of these complex resources across the university to disciplines as diverse as Mathematics, Health, Information Systems and Creative Industries. •Has demonstrated clear concrete support for research by QUT Library and built relationships into faculty. It has made data available to all researchers and attracted new HDRs. The aim is to reach the output threshold of research outputs to submit into FOR Code 1502 (Banking, Finance and Investment) for ERA 2015. •It is difficult to identify what subset of dataset will be obtained given somewhat vague price tiers. •The integrity of data is variable as it is limited by the way it is collected, this occasionally raises issues for researchers(Cook, Campbell, & Kelly, 2012) •Improved library understanding of the content of our products and the nature of financial based research is a necessary part of the service.

Talking the talk : therapeutic jurisprudence and oral competence

In Australian criminal justice systems, a wide range of pathways to sentencing and punishment exist alongside traditional court processes. In particular, therapeutic jurisprudence ('TJ') processes have emerged during the last quarter of a century and now occupy a key position in the criminal justice landscape. This article provides an introduction to TJ, highlighting in particular the emphasis it places on the active participation of offenders, before critically discussing offenders' capacity to engage with TJ processes. The article then summarises the research on the oral competence of offenders, and argues that offenders who lack oral competence may be disadvantaged in TJ processes. Finally, we provide an overview of the limited guidance that has been provided to TJ practitioners on how to maximise the participation of offenders with limited oral competence.

Bail and remand for young people in Australia : a national research project

Funded and endorsed by the Australasian Juvenile Justice Administrators, this is one of the first national scale research reports into the bail and remand practices for young Australians. A young person can be placed in custody on remand (ie refused bail) after being arrested by police in relation to a suspected criminal offence, before entering a plea, while awaiting trial, during trial or awaiting sentence. Although custodial remand plays an important role in Western criminal justice systems, minimising the unnecessary use of remand is important given the obligations Australia has under several UN instruments to use, as a last resort, youth detention of any kind. This research identifies trends in the use of custodial remand and explores the factors that influence its use for young people nationally and in each of Australia’s jurisdictions.

Misperceptions about child sex offenders

Sexual offending against children is a highly emotive issue. It is nonetheless important that public policy initiatives to prevent and/or respond to child sexual abuse are based on the available evidence about child sex offenders. This paper addresses five common misperceptions about the perpetrators of sexual offences against children. Specifically, the issues addressed include whether all child sex offenders are ‘paedophiles’, who sexually abuse children, whether most child sex offenders were victims of sexual abuse themselves, rates of recidivism among child sex offenders and the number of children sex offenders typically abuse before they are detected by police. The evidence outlined in this paper highlights that there are few black and white answers to these questions. Perpetrators of sexual crimes against children are not, contrary to widespread opinion, a homogenous group. Rather, there are a number of varied offending profiles that characterise child sex offenders. Gaining an understanding of the nuances of this offender population is critical if children are to be protected from sexual abuse.

Computer security incidents against Australian businesses : predictors of victimisation

Drawing on data from the Australian Business Assessment of Computer User Security (ABACUS) survey, this paper examines a range of factors that may influence businesses’ likelihood of being victimised by a computer security incident. It has been suggested that factors including business size, industry sector, level of outsourcing, expenditure on computer security functions and types of computer security tools and/or policies used may influence the probability of particular businesses experiencing such incidents. This paper uses probability modelling to test whether this is the case for the 4,000 businesses that responded to the ABACUS survey. It was found that the industry sector that a business belonged to, and business expenditure on computer security, were not related to businesses’ likelihood of detecting computer security incidents. Instead, the number of employees that a business has and whether computer security functions were outsourced were found to be key indicators of businesses’ likelihood of detecting incidents. Some of the implications of these findings are considered in this paper.

Child complainants and the court process in Australia

In recent years, it has been recognised that child complainants in the criminal justice system can experience difficulties over and above those of other complainants and that children can experience the court process as extremely traumatising. This can be exacerbated if children are complainants in child sexual offence matters and if they have to give evidence against a family member. This paper has three primary aims. First, it outlines the major factors that contribute to making court processes harrowing for child complainants. Second, it outlines some of the main initiatives that have been introduced to address these factors. Finally, it weighs up the evidence about initiatives designed to assist child complainants and concludes that such initiatives have had only limited practical impact for child complainants in the criminal justice system. The limited impact is attributed to the need to balance the rights of the accused with consideration for the complainant, a failure to translate legislative changes into practice, the impact of judicial discretion and/or a focus on protecting child complainants at the expense of increasing convictions.

Crime, justice and social democracy : proceedings of the second international conference, 2013, volume 1

The refereed papers contained in this set of conference proceedings were presented at the 2nd International Conference on Crime, Justice and Social Democracy, hosted by the Crime and Justice Research Centre, Faculty of Law, QUT. The conference attracted an impressive list of internationally distinguished keynote and panel speakers from the United Kingdom, United States, Australia, New Zealand, Canada and this time Latin America, as well as high quality paper submissions.

Re-imagining youth justice

Persistent high levels of recidivism among young offenders (Luke and Lind 2002; Weatherburn et al. 2012) and the over‐representation of Indigenous young people (Cunneen and White 2011; Snowball 2008; Tauri 2012) have long been features of youth justice in Australia. Other problems – such as the increased rates of young people committing sex offences (Dwyer 2011; O’Brien 2010), increasing numbers of young people criminalised for new offences such as ‘sexting’ (Lee and McGovern 2013), and increasing numbers of young female offenders being drawn into youth justice systems (Carrington 2006; Carrington and Pereira 2009) – have emerged more recently. In this paper, we draw on the concept of ‘imaginary penalities’ (Carlen 2010) to argue these chronic problems are partly informed by ‘imaginary’ understandings of how and why young people (re)offend; reflect ‘imaginary’ understandings of what works to address young people’s (re)offending; and reflect ‘imaginary’ ideals about the primary purposes of the youth justice system. We acknowledge up front that answers to these questions require a great deal of new empirical research. This paper is only a beginning that sets out exactly what such an ambitious project might look like.