Mechanisms of mono- and poly-ubiquitination : ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine

Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3 s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a catalytic level, ubiquitination of lysine residues within the substrate or ubiquitin occurs by nucleophilic attack of the lysine residue on the thioester bond linking the E2 catalytic cysteine to ubiquitin. One of the best studied RING E3/ E2 complexes is the Skp1/Cul1/F box protein complex, SCFCdc4, and its cognate E2, Cdc34, which target the CDK inhibitor Sic1 for K48-linked polyubiquitination, leading to its proteasomal degradation. Our recent studies of this model system demonstrated that residues surrounding Sic1 lysines or lysine 48 in ubiquitin are critical for ubiquitination. This sequence-dependence is linked to evolutionarily conserved key residues in the catalytic region of Cdc34 and can determine if Sic1 is mono- or poly-ubiquitinated. Our studies indicate that amino acid determinants in the Cdc34 catalytic region and their compatibility to those surrounding acceptor lysine residues play important roles in lysine selection. This may represent a general mechanism in directing the mode of ubiquitination in E2 s.

The work of Media Arts in the age of digital production

This chapter uses as a beginning point Walter Benjamin’s famous essay ‘The work of art in the age of technological reproducibility’(1935/2008) to discuss Media Arts education. It locates ‘Media Arts’ at the intersection of three key ideas: 1) media arts products as objects for popular and everyday consumption and intervention by individuals and broader audiences; 2) materiality and how individuals use their bodies and technologies to produce, combine and share digital materials and; 3) the construction of aesthetic knowledge and how this relates to critical and conceptual thinking. These ideas are discussed in the context of the development of curriculum for students at all ages of schooling, with specific attention given to the knowledge and skills students might develop within Media Arts education in primary schools. Examples from a Media Arts project in a primary school in Australia – where a new Media Arts national curriculum has been developed –are provided to illustrate the key ideas discussed in the chapter.

Connecting two wind turbine generators to the grid using only one three level NPC inverter

This paper explores the possibility of connecting two Wind Turbine Generators (WTG) to the grid using a single three level inverter. In the proposed system the rectified output of one WTG is connected across the upper dc-link capacitor of a standard diode clamped three level inverter. Similarly the rectified output of the other WTG is connected across the lower capacitor. This particular combination has several advantages such as, direct connection to the grid, reduced parts count, improved reliability and high power capacity. However, the major problem in the proposed system is the imminent imbalance of dc-link voltages. Under such conditions conventional modulation methods fail to produce desired voltage and current waveforms. A detailed analysis on this issue and a novel space vector modulation method, as the solution, are proposed in this paper. To track the Maximum power point of each WTG a power sharing algorithm is proposed. Simulation results are presented to attest the efficacy of the proposed system.

Author response to : Brough et al. in response to the recently published article : Lottering,N., MacGregor,D.M.,Barry,M.D.,Reynolds,M.S., Gregory,L.S., 2014. Introducing standardized protocols for anthropological measurement of virtual sub-adult crania using computed tomography 2(1),34–38

Firstly, we would like to thank Ms. Alison Brough and her colleagues for their positive commentary on our published work [1] and their appraisal of our utility of the “off-set plane” protocol for anthropometric analysis. The standardized protocols described in our manuscript have wide applications, ranging from forensic anthropology and paleodemographic research to clinical settings such as paediatric practice and orthopaedic surgical design. We affirm that the use of geometrically based reference tools commonly found in computer aided design (CAD) programs such as Geomagic Design X® are imperative for more automated and precise measurement protocols for quantitative skeletal analysis. Therefore we stand by our recommendation of the use of software such as Amira and Geomagic Design X® in the contexts described in our manuscript...

Regulating Work

This chapter examines the regulation of ‘work’: principally the circumstances in which labour is engaged and the conditions attaching to the work relationships which are consequently formed and carried on. Fundamentally, this is the subject area labelled ‘labour law’in modern-day legal, academic, and professional discourse. This chapter also explores how some issues in the regulatory literature impact upon this field. One of the central arguments in this chapter is that instrumental regulation in the field of labour law is not a relatively modern phenomenon. Rather, the reading of the historical literature pertaining to labour under earlier economic and social conditions shows that the instrumental regulation of the labour market by the state and its courts has been the dominant form of law in this field for centuries. Readership: academics working on any area of law or in socio-legal research

Australian health and safety inspectors’ perceptions and actions in relation to changed work arrangements

Extensive international research points to an association between changed work arrangements, especially those commonly labelled as contingent work, with adverse occupational health and safety (OHS) outcomes. Research also indicates these work arrangements have weakened or bypassed existing OHS and workers’ compensation regulatory regimes. However, there has been little if any research into how OHS inspectors perceive these issues and how they address them during workplace visits or investigations. Between 2003 and 2007 research was undertaken that entailed detailed documentary and statistical analysis, extended interviews with 170 regulatory managers and inspectors, and observational data collected while accompanying inspectors on 118 ‘typical’ workplace visits. Key findings are that inspectors responsible for a range of industries see altered work arrangements as a serious challenge, especially labour hire (agency work) and subcontracting. Though the law imposes clear obligations, inspectors identified misunderstanding/blameshifting and poor compliance amongst parties to these arrangements. The complexity of these work arrangements also posed logistical challenges to inspectorates.

Engaging expert contractors: The work health and safety obligations of the business or undertaking

This article examines the legal principles governing the statutory work health and safety general duties of principals who engage expert contractors to carry out work beyond the expertise of the principal. The article examines recent case law in which superior courts accepted the principal’s argument that the engagement of the expert contractor was sufficient to discharge the principal’s statutory work health and safety general duty. It then reframes the debate within the principles of systematic work health and safety management, and key provisions in the harmonised Work Health and Safety Acts—the primary duty of care; the key underpinning principles; the positive and proactive officer’s duty; and the horizontal duty of consultation, cooperation and coordination. It argues that it is likely that courts examining the issue of the principal’s work health and safety obligations under the harmonised Work Health and Safety Acts will require principals to do more to actively manage the work of expert contractors to ensure the health and safety of all workers and others potentially affected by the work.

The contribution of major depression to the global burden of ischemic heart disease : a comparative risk assessment

Background Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology. Methods A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010. Results The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest. Conclusions The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event.

The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study

Aim Estimate the prevalence of cannabis dependence and its contribution to the global burden of disease. Methods Systematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated. Results There were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally. Conclusion Cannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.

Environmental contributions to the leading causes of disease burden among Australian children

Although the effect of adverse environments on the well-being of children is an important global health issue, it remains underrecognized in health care and underconsidered in terms of both research and public policy. Children have developmentally distinct patterns of environmental exposure and susceptibilities that increase their risk of disease. Young children, especially those who are impoverished, have disproportionately heavier exposures to environmental threats in a given environment. They also have decreased metabolic capacity to detoxify and eliminate contaminants. Furthermore, rapid growth and development before and after birth and the continuing growth and postnatal maturation of the respiratory, immune, and neurological systems, in particular, make them increasingly vulnerable to environmental threats...

Veracity of the archive : a research approach to the collection and verification of urban morphological records using qualitative data analysis software

Critical to the research of urban morphologists is the availability of historical records that document the urban transformation of the study area. However, thus far little work has been done towards an empirical approach to the validation of archival data in this field. Outlined in this paper, therefore, is a new methodology for validating the accuracy of archival records and mapping data, accrued through the process of urban morphological research, so as to establish a reliable platform from which analysis can proceed. The paper particularly addresses the problems of inaccuracies in existing curated historical information, as well as errors in archival research by student assistants, which together give rise to unacceptable levels of uncertainty in the documentation. The paper discusses the problems relating to the reliability of historical information, demonstrates the importance of data verification in urban morphological research, and proposes a rigorous method for objective testing of collected archival data through the use of qualitative data analysis software.

Temporal characteristics of melanopsin inputs to the human pupil light reflex

Rods, cones and melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons cm(-2) s(-1)). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

The contribution of ISO 14067 to the evolution of global greenhouse gas standards—A review

Due to the increasing recognition of global climate change, the building and construction industry is under pressure to reduce carbon emissions. A central issue in striving towards reduced carbon emissions is the need for a practicable and meaningful yardstick for assessing and communicating greenhouse gas (GHG) results. ISO 14067 was published by the International Organization for Standardization in May 2013. By providing specific requirements in the life cycle assessment (LCA) approach, the standard clarifies the GHG assessment in the aspects of choosing system boundaries and simulating use and end-of-life phases when quantifying carbon footprint of products (CFPs). More importantly, the standard, for the first time, provides step-to-step guidance and standardized template for communicating CFPs in the form of CFP external communication report, CFP performance tracking report, CFP declaration and CFP label. ISO 14067 therefore makes a valuable contribution to GHG quantification and transparent communication and comparison of CFPs. In addition, as cradle-to-grave should be used as the system boundary if use and end-of-life phases can be simulated, ISO 14067 will hopefully promote the development and implementation of simulation technologies, with Building Information Modelling (BIM) in particular, in the building and construction industry.

But how do we know they watched it? Adapting to the flipped classroom conundrum

Those who teach film and media need to use screen content to illustrate their subjects. For example, students want illustrations to accompany lectures on film or television genres. Our experience has been that student access to the film and television screen content underpinning a study of genres is not only desirable but is, in fact, crucial for effective teaching and learning outcomes. Not so long ago, a screening during or at the completion of a lecture was the expected method by which educators delivered screen content to illustrate their teaching. Even if student attendance fluctuated from week to week a quick head count confirmed that a certain number of students were physically present. It was assumed that this physical attendance encouraged students to reflect upon and contextualize the material post lecture. While simply attending a lecture will not translate into actual student learning, it does demonstrate a willingness by students to engage with the course content by making a commitment to attend a scheduled and recurring lecture and screening program. However, as flipped classroom models gain acceptance in educational institutions, this traditional lecture-screening model is giving way to online, off-site, and student-controlled mechanisms for screen content delivery and viewing. Nevertheless, care should be taken when assessing how online delivery translates into student engagement and learning. As Junco (2012) points out, “it’s not the technology that generates learning, but the ways in which the technology are used.” Discussed, debated, and embraced to varying degrees by educators, there remains no definitive model for the flipped classroom – although many models involve ‘flipping’ content and knowledge acquisition (including viewing films and television shows) from scheduled on-campus classes to online material viewed by students in advance of an on-campus lecture or class. The classroom or tutorial room then becomes a space to problem-solve, engage in collaborate learning, and advance and explain concepts. From an institutional perspective, the flipped classroom model could deliver an additional benefit beyond immediate pedagogical concerns. Tucker (2012) suggests through the flipped classroom model “all aspects of instruction can be rethought to best maximize the scarcest learning resource — time.” The narrative most often associated with this shift is that the move to online content delivery of lecture and cinematic / televisual material may also provide educators with more time to do other work such as engage in research, plan strategies to empower students. Experimentation with the flipped classroom model is playing out in various educational institutions. Yet several core concerns remain — one of these concerns is the crucial question of whether an online/digital flipped approach is more effective for student engagement and learning than the traditional lecture-screening mode for screen content delivery. Some urge caution in this regard, arguing that “new technology isn’t always supported by change management and professional development to ensure that digital isn’t just a goal within itself, but actually helps to transform education” (Fleming cited in Blain 2014). The most fundamental concern remains how do lecturers, instructors, and tutors know students have watched the films and television shows associated with a subject? The remainder of this discussion deals with these concerns, and possible solutions offered, through an analysis of the Film, Television and Screen Genres subject at the Queensland University of Technology (QUT) in Brisbane, Queensland.

Evaluation of ANPR trials for traffic policing in Queensland. Report to the Queensland Police Service, State Traffic Support Branch

In response to the Travelsafe Committee Report No. 51 – report on the inquiry into Automatic Plate Recognition Technology – it was recommended that the Queensland Police Service continue to trial the deployment of ANPR technology for traffic enforcement work and to evaluate the road safety impacts and operational effectiveness of the technology. As such, the purpose of this report is to provide an independent evaluation of a trial of ANPR that was conducted by a project team within the State Traffic Support Branch of the Queensland Police Service (QPS) and provide recommendations as to the applicability and usability of the technology for use throughout Queensland...