Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

Risk-based approach to the management of on-site wastewater treatment facilities

Background On-site wastewater treatment system (OWTS) siting, design and management has traditionally been based on site specific conditions with little regard to the surrounding environment or the cumulative effect of other systems in the environment. The general approach has been to apply the same framework of standards and regulations to all sites equally, regardless of the sensitivity, or lack thereof, to the receiving environment. Consequently, this has led to the continuing poor performance and failure of on-site systems, resulting in environmental and public health consequences. As a result, there is increasing realisation that more scientifically robust evaluations in regard to site assessment and the underlying ground conditions are needed. Risk-based approaches to on-site system siting, design and management are considered the most appropriate means of improvement to the current standards and codes for on-site wastewater treatment systems. The Project Research in relation to this project was undertaken within the Gold Coast City Council region, the major focus being the semi-urban, rural residential and hinterland areas of the city that are not serviced by centralised treatment systems. The Gold Coast has over 15,000 on-site systems in use, with approximately 66% being common septic tank-subsurface dispersal systems. A recent study evaluating the performance of these systems within the Gold Coast area showed approximately 90% were not meeting the specified guidelines for effluent treatment and dispersal. The main focus of this research was to incorporate strong scientific knowledge into an integrated risk assessment process to allow suitable management practices to be set in place to mitigate the inherent risks. To achieve this, research was undertaken focusing on three main aspects involved with the performance and management of OWTS. Firstly, an investigation into the suitability of soil for providing appropriate effluent renovation was conducted. This involved detailed soil investigations, laboratory analysis and the use of multivariate statistical methods for analysing soil information. The outcomes of these investigations were developed into a framework for assessing soil suitability for effluent renovation. This formed the basis for the assessment of OWTS siting and design risks employed in the developed risk framework. Secondly, an assessment of the environmental and public health risks was performed specifically related the release of contaminants from OWTS. This involved detailed groundwater and surface water sampling and analysis to assess the current and potential risks of contamination throughout the Gold Coast region. Additionally, the assessment of public health risk incorporated the use of bacterial source tracking methods to identify the different sources of fecal contamination within monitored regions. Antibiotic resistance pattern analysis was utilised to determine the extent of human faecal contamination, with the outcomes utilised for providing a more indicative public health assessment. Finally, the outcomes of both the soil suitability assessment and ground and surface water monitoring was utilised for the development of the integrated risk framework. The research outcomes achieved through this project enabled the primary research aims and objects to be accomplished. This in turn would enable Gold Coast City Council to provide more appropriate assessment and management guidelines based on robust scientific knowledge which will ultimately ensure that the potential environmental and public health impacts resulting from on-site wastewater treatment is minimised. As part of the implementation of suitable management strategies, a critical point monitoring program (CPM) was formulated. This entailed the identification of the key critical parameters that contribute to the characterised risks at monitored locations within the study area. The CPM will allow more direct procedures to be implemented, targeting the specific hazards at sensitive areas throughout Gold Coast region.

A model for curricula integration using the Australian curriculum

Targeting students’ learning is at the centre of education. In addition, education is promoted as a solution on various issues; consequently educators seek ways for teachers to address societal needs, students’ learning needs, and the overcrowded curriculum. There are definition debates and issues around integrating curricula. However, the rationale for primary students undertaking curricula integrated learning can provide motivation for primary teachers to devise and implement curricula integrated lessons in the classroom. More exploration is required to present models for the practical implementation of curricula integration. This paper provides practical ideas for curricula integration that focus on combining achievement standards from the Australian Curriculum: Science and other key learning areas.

Do people gamble with their lives : The relationship between risky driving behaviour and other risky behaviours

General risky behaviour is explored for correlation with risky driving behaviour in light of two theories, self-control and cross-situational consistency. Identification of general risky behaviours associated with risky driving behaviour, and the theory that best predicts the behaviours, will enable better targeting of intervention and education strategies to reduce driving related fatalities and injuries. A correlational study using participants (N=152) drawn from first year university undergraduates and the public surveyed their lifestyle and behaviours. Relationships were found between risky driving behaviours and other risky behaviours such as alcohol consumption, cannabis use and performing unlawful activities. No significant differences were found between genders, with the exception that males were more likely to believe that they were at risk of injury from their employment, χ2 (1, N = 152) = 4.49, p = .03, were more likely to have performed an unlawful offence, χ2 (1, N = 152) = 11.77, p = .001 and were more likely to drink drive, t (55.41) = -3.87, p < .001, mean difference = -0.63, CI 95% (-0.9, -0.37). People engaged in risky driving behaviours were more likely to engage in other risky behaviours. The theories that were explored were unable to accurately predict an association between general risky behaviour and driving without a license or when disqualified. Cross-situational consistency explained 20% (R2adj = .16) of the variance in which people engaged in risky driving with low self-control theory explaining an additional 0.3% variance (R2change = .003), F (8,143) = 6.92, p < .001. Driving while under the influence of alcohol could be predicted by risky behaviours in lifestyle, health, smoking, cannabis use and alcohol consumption, F (8,143) = 6.92, p < .001. The addition of self-control was not significant.

Mission drift or strategic shift? Group formation strategies within MEPs

Microenterprise development programs (MEPs) have been recognised as a valuable way to help the poor engage in micro-businesses (Green et al., 2006; Vargas, 2000), presenting a way out of poverty (Choudhury et al., 2008; Strier, 2010). Concerns have been raised however, that the benefits of MEPs often don’t reach the extremely poor (Jones et al., 2004; Midgley, 2008; Mosley and Hulme, 1998; Nawaz, 2010; Pritchett, 2006). Balancing reach of these programs with depth is a challenging task. Targeting as many poor people as possible often results in MEPs focusing on the upper or middle poor, overlooking the most challenging group. As such, MEPs have been criticised for mission drift – losing sight of the organisation’s core purpose; assisting those more likely to succeed.

An introduction to biologics

An introduction to biologics 23.1 Introduction: Principles of biologics and their use as medicines 23.2 Protein biologics used as drugs 23.2.1 Proteins that function through enzymatic or regulatory activity. 23.2.1.1 Biologics as replacement of a deficient or abnormal protein. 23.2.1.2 Proteins that augment an existing biological process. 23.2.1.3 Proteins that provide a novel function or activity. 23.2.2. Proteins that function through specific targeting activity. 23.2.2.1. Monoclonal antibody nomenclature. 23.2.2.2. Naked monoclonal antibodies. 23.2.2.3. Conjugated monoclonal antibodies. 23.2.3. Recombinant protein vaccines.

Optimization of human papillomavirus type 16 (HPV-16) L1 expression in plants: Comparison of the suitability of different HPV-16 L1 gene variants and different cell-compartment localization

Virus-like particle-based vaccines for high-risk human papillomaviruses (HPVs) appear to have great promise; however, cell culture-derived vaccines will probably be very expensive. The optimization of expression of different codon-optimized versions of the HPV-16 L1 capsid protein gene in plants has been explored by means of transient expression from a novel suite of Agrobacterium tumefaciens binary expression vectors, which allow targeting of recombinant protein to the cytoplasm, endoplasmic reticulum (ER) or chloroplasts. A gene resynthesized to reflect human codon usage expresses better than the native gene, which expresses better than a plant-optimized gene. Moreover, chloroplast localization allows significantly higher levels of accumulation of L1 protein than does cytoplasmic localization, whilst ER retention was least successful. High levels of L1 (>17% total soluble protein) could be produced via transient expression: the protein assembled into higher-order structures visible by electron microscopy, and a concentrated extract was highly immunogenic in mice after subcutaneous injection and elicited high-titre neutralizing antibodies. Transgenic tobacco plants expressing a human codon-optimized gene linked to a chloroplast-targeting signal expressed L1 at levels up to 11% of the total soluble protein. These are the highest levels of HPV L1 expression reported for plants: these results, and the excellent immunogenicity of the product, significantly improve the prospects of making a conventional HPV vaccine by this means. © 2007 SGM.

The capsid protein of beak and feather disease virus binds to the viral DNA and is responsible for transporting the replication-associated protein into the nucleus

Circoviruses lack an autonomous DNA polymerase and are dependent on the replication machinery of the host cell for de novo DNA synthesis. Accordingly, the viral DNA needs to cross both the plasma membrane and the nuclear envelope before replication can occur. Here we report on the subcellular distribution of the beak and feather disease virus (BFDV) capsid protein (CP) and replication-associated protein (Rep) expressed via recombinant baculoviruses in an insect cell system and test the hypothesis that the CP is responsible for transporting the viral genome, as well as Rep, across the nuclear envelope. The intracellular localization of the BFDV CP was found to be directed by three partially overlapping bipartite nuclear localization signals (NLSs) situated between residues 16 and 56 at the N terminus of the protein. Moreover, a DNA binding region was also mapped to the N terminus of the protein and falls within the region containing the three putative NLSs. The ability of CP to bind DNA, coupled with the karyophilic nature of this protein, strongly suggests that it may be responsible for nuclear targeting of the viral genome. Interestingly, whereas Rep expressed on its own in insect cells is restricted to the cytoplasm, coexpression with CP alters the subcellular localization of Rep to the nucleus, strongly suggesting that an interaction with CP facilitates movement of Rep into the nucleus. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A rep-based hairpin inhibits replication of diverse maize streak virus isolates in a transient assay

Centre for High-Performance Computing, Rosebank, Cape Town, South Africa Maize streak disease, caused by the A strain of the African endemic geminivirus, maize streak mastrevirus (MSV-A), threatens the food security and livelihoods of subsistence farmers throughout sub-Saharan Africa. Using a well-established transient expression assay, this study investigated the potential of a spliceable-intron hairpin RNA (hpRNA) approach to interfere with MSV replication. Two strategies were explored: (i) an inverted repeat of a 662 bp region of the MSV replication-associated protein gene (rep), which is essential for virus replication and is therefore a good target for post-transcriptional gene silencing; and (ii) an inverted repeat of the viral long intergenic region (LIR), considered for its potential to trigger transcriptional silencing of the viral promoter region. After co-bombardment of cultured maize cells with each construct and an infectious partial dimer of the cognate virus genome (MSV-Kom), followed by viral replicativeform-specific PCR, it was clear that, whilst the hairpin rep construct (pHPrepDI662) completely inhibited MSV replication, the LIR hairpin construct was ineffective in this regard. In addition, pHPrepDI662 inhibited or reduced replication of six MSV-A genotypes representing the entire breadth of known MSV-A diversity. Further investigation by real-time PCR revealed that the pHPrepDI662 inverted repeat was 22-fold more effective at reducing virus replication than a construct containing the sense copy, whilst the antisense copy had no effect on replication when compared with the wild type. This is the first indication that an hpRNA strategy targeting MSV rep has the potential to protect transgenic. © 2011 SGM.

Increasing physical activity among women with young children: Results from the Proactive Mums Project

Context Evidence from the Australian Longitudinal Study of Women's Health suggests that mothers of young children have lower levels of physical activity (PA) than women of similar age without children. Objectives The aim of the ProActive Mums project was to determine the relative efficacy of two strategies designed to increase the proportion of mothers of young children who are meeting current PA guidelines, utilising child care centres (CCCs) as the setting for recruitment. Study Design The project used a randomised (after stratification to ensure even representation of CCCs from differing socio-economic areas) design incorporating repeated data collection from women in three groups, each consisting of 7 childcare centres (CCCs). Baseline surveys were completed by 554 mothers, with follow-up data collection immediately post-Intervention (8 weeks after baseline) and again 5 months later. Women from CCCs in Group 1 (control) received only the surveys throughout the duration of the project. Women from CCCs in Group 2 (information only) were given a print intervention, and women from CCCs in Group 3 were (in addition to being given the same print intervention as women from CCCs in Group 2) invited to to contribute to the development of, and participate in, strategies for the promotion of PA among mothers of young children. The two intervention strategies were extensively evaluated through a series of surveys and interviews. The Intervention The print intervention prescribed for women from CCCs in Group 2 and Group 3 consisted of an 8-page booklet containing motivational messages and information about physical activity. Women from CCCs in Group 3 were also invited to attend meetings at their CCC to identify strategies for increasing their PA. Contacts were made with key stakeholders in the community, including managers of sporting and recreation facilities, childcare service providers, and local councils. A wide range of strategies was developed during the intervention phase of the project, which specifically focused on the need to increase partner support and self-efficacy (or the confidence to be physically active). Results The mean age of participants was 33 (+ 4.8) years, and the mean number of children per family unit was 2.2 (± 0.9). At baseline, fewer than half the women were meeting current guidelines for adequate PA for health benefit, and there were no significant differences between groups in the proportion of women who were adequately active for health benefit. Women in Group 3 were significantly more likely to meet the guidelines at post-intervention follow-up than controls [OR = 1.71 (1.05-2.77)] after controlling for age and PA at baseline. There was no significant effect of the print intervention alone on meeting guidelines at post-intervention follow-up compared with controls, after controlling for age and PA at baseline [OR = 1.15 (0.70-1.89)]. Changes in Partner Support (PS) and Self Efficacy (SE) significantly predicted meeting current PA guidelines at post-intervention follow-up after controlling for baseline PA [∆ PS: OR = 2.29 (1.46-3.58); ∆ SE: OR = 1.86 (1.17- 2.94)]. The intervention effect in Group 3 was not maintained at long-term follow-up. Conclusions The findings indicate that a community participation approach that facilitates increased partner support and self-efficacy can be effective in increasing PA among mothers of young children. Changes in physical activity were found to be mediated by changes in partner support and self-efficacy for physical activity, suggesting that the intervention successfully targeted the individual characteristics it intended to, and that these variables do play an important role in increasing physical activity among women with young children. It is clear that further work needs to be done to explore methods of translating the short-term intervention effect shown in this study into long-term changes in PA behaviour. This study also provided insight into measurement issues in PA research and raised questions about self-report measures of PA and perceived constraints to being physically active. The results from post-study qualitative interviews suggest that many women at this life-stage experience time constraints which, when accompanied by a lack of partner support and financial constraints, make leisure-time PA virtually impossible for many women. Future strategies might focus on targeting this population immediately prior to this life-stage in an attempt to encourage habitual physical activity before women have children. Increasing PA in this population should also address the entire family unit, and consider the way leisure-time is negotiated among the adults within a household. Social change and increased awareness of the range of benefits of PA for women with children are additional strategies to be considered.

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.

Bioreactor for blood product production

The feasibility of ex vivo blood production is limited by both biological and engineering challenges. From an engineering perspective, these challenges include the significant volumes required to generate even a single unit of a blood product, as well as the correspondingly high protein consumption required for such large volume cultures. Membrane bioreactors, such as hollow fiber bioreactors (HFBRs), enable cell densities approximately 100-fold greater than traditional culture systems and therefore may enable a significant reduction in culture working volumes. As cultured cells, and larger molecules, are retained within a fraction of the system volume, via a semipermeable membrane it may be possible to reduce protein consumption by limiting supplementation to only this fraction. Typically, HFBRs are complex perfusion systems having total volumes incompatible with bench scale screening and optimization of stem cell-based cultures. In this article we describe the use of a simplified HFBR system to assess the feasibility of this technology to produce blood products from umbilical cord blood-derived CD34+ hematopoietic stem progenitor cells (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where cells are cultured in the extracapillary space, we have cultured cells in the intracapillary space, which is likely more compatible with the large-scale production of blood cell suspension cultures. Using this platform we direct HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell density and the use of protein-free bulk medium. Our results demonstrate the potential of this system to deliver high cell densities, even in the absence of protein supplementation of the bulk medium.

Managing older workers during a period of tight labour supply

This article reports on a recent survey of employer attitudes and policies towards older workers in Australia at a time of sustained economic growth and ongoing concerns about labour shortages. Findings from a survey of 590 employers with more than 50 employees in the State of Queensland point to an unusually strong orientation towards the recruitment of older workers among respondents, although the retraining of older workers is not prioritised by the majority. The issue of workforce ageing is viewed as being of medium-term importance by the majority of respondents, although for a substantial number the issue is of immediate concern. Both sector and organisation size are predictive of the application of a broad range of policies targeting older workers, with public-sector and larger organisations more likely to be active. Concerns about workforce ageing and labour supply are predictive of employer behaviours regarding older workers, suggesting that sustained policy making may be emerging in response to population ageing over and above more immediate concerns about labour shortages and that this broad thrust of organisational policy making may be immune to the point in the economic cycle. This study found no evidence that the flexible firm will not countenance an ageing workforce.

Catapulting into STEM education : female students’ interactions within a middle school engineering project

Despite efforts to motivate students to engage in Science, technology, engineering and mathematics (STEM) education, women are still underrepresented in these areas in the workforce and higher education. Targeting females at high school or earlier may be a key towards engaging them in STEM. In this paper we report on the research question: How do middle school females interact for learning about engineering education? This ethnographic study, part of a three-year longitudinal research project, investigated Year 8 female students’ learning about engineering concepts associated with designing, constructing, testing, and evaluating a catapult. Through a series of lead-up lessons and the four lesson catapult challenge (total of 18 x 45-minute lessons over 9 weeks), data from two girls within a focus group showed that the students needed to: (1) receive clarification on engineering terms to facilitate more fluent discourse, (2) question and debate conceptual understandings without peers being judgemental, and (3) have multiple opportunities for engaging with materials towards designing, constructing and explaining key concepts learnt. Implications for teachers undertaking STEM education are evident, including outlining expectations for clarifying STEM terms, outlining to students about interacting non-judgementally, and providing multiple opportunities for interacting within engineering education.

Who succeeds at university? factors predicting academic performance in first year Australian university students

With the increasing diversity of students attending university, there is a growing interest in the factors predicting academic performance. This study is a prospective investigation of the academic, psychosocial, cognitive, and demographic predictors of academic performance of first year Australian university students. Questionnaires were distributed to 197 first year students 4 to 8 weeks prior to the end of semester exams and overall grade point averages were collected at semester completion. Previous academic performance was identified as the most significant predictor of university performance. Integration into university, self efficacy, and employment responsibilities were also predictive of university grades. Identifying the factors that influence academic performance can improve the targeting of interventions and support services for students at risk of academic problems.