Regulation of proteasome structure and function

Proteasomes are cylindrical particles made up of a stack of four heptameric rings. In animal cells the outer rings are made up of 7 different types of alpha subunits and the inner rings are composed of 7 out of 10 possible different beta subunits. Regulatory complexes can bind to the ends of the cylinder.We have investigated aspects of the assembly, activity and subunit composition of core proteasome particles and 26S proteasomes, the localization of proteasome subpopulations, and the possible role of phosphorylation in determining proteasome localization, activities and association with regulatory components.

Catalytic components of proteasomes and the regulation of proteinase activity

The proteasome (multicatalytic proteinase complex) is a large multimeric complex which is found in the nucleus and cytoplasm of eukaryotic cells. It plays a major role in both ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways of protein degradation. Proteasome subunits are encoded by members of the same gene family and can be divided into two groups based on their similarity to the c~ and /3 subunits of the simpler proteasome isolated from Thermoplasma acidophilum. Proteasomes have a cylindrical structure composed of four rings of seven subunits. The 26S form of the proteasome, which is responsible for ubiquitin-dependent proteolysis, contains additional regulatory complexes. Eukaryotic proteasomes have multiple catalytic activities which are catalysed at distinct sites. Since proteasomes are unrelated to other known proteases, there are no clues as to which are the catalytic components from sequence alignments. It has been assumed from studies with yeast mutants that /3-type subunits play a catalytic role. Using a radiolabelled peptidyl chloromethane inhibitor of rat liver proteasomes we have directly identified RC7 as a catalytic component. Interestingly, mutants in Prel, the yeast homologue of RC7, have already been reported to have defective chymotrypsin-like activity. These results taken together confirm a direct catalytic role for these/3-type subunits. Proteasome activities are sensitive to conformational changes and there are several ways in which proteasome function may be modulated in vivo. Our recent studies have shown that in animal cells at least two proteasome subunits can undergo phosphorylation, the level of which is likely to be important for determining proteasome localization, activity or ability to form larger complexes. In addition, we have isolated two isoforms of the 26S proteinase.

Environmental reporting in the Australian mining industry : complying with regulation or meeting international best practice?

It is nearly 10 years since the introduction of s 299(1)(f) Corporations Act , which requires the disclosure of information regarding a company's environmental performance within its annual report. This provision has generated considerable debate in the years since its introduction, fundamentally between proponents of either a voluntary or mandatory environmental reporting framework. This study examines the adequacy of the current regulatory framework. The environmental reporting practices of 24 listed companies in the resources industries are assessed relative to a standard set by the Global Reporting Initiative (GRI) Sustainability Reporting Guidelines. These Guidelines are argued to represent "international best practice" in environmental reporting and a "scorecard" approach is used to score the quality of disclosure according to this voluntary benchmark. Larger companies in the sample tend to report environmental information over and above the level required by legislation. Some, but not all companies present a stand-alone environmental/sustainability report. However, smaller companies provide minimal information in compliance with s 299(1)(f) . The findings indicate that "international best practice" environmental reporting is unlikely to be achieved by Australian companies under the current regulatory framework. In the current regulatory environment that scrutinises s 299(1)(f) , this article provides some preliminary evidence of the quality of disclosures generated in the Australian market.

Speed enforcement in Australia : a changing policy landscape shaped by public opinion

- Speeding and crash involvement in Australia - Speed management in Australia - Jurisdictional differences - National Road Safety Strategy (2011-2020) - Auditor-General reviews of speed camera programs - The role of public opinion/feedback - Implications for speed management

The Waitangi Tribunal and the regulation of Maori protest

Much of the current academic and political discourse related the development and operations of the Waitangi Tribunal over its first twenty years portray it as a forum that provided Māori with a meaningful avenue for settling Treaty grievances compared to the formal legal systems performance in the preceding 100 years. In contrast, we argue that from its inception and throughout much of the 1980s, the Waitangi Tribunal functioned primarily as an informal justice forum that assisted the New Zealand state’s regulation of Māori Treaty activism during the transition from a Fordist to a Post-Fordist mode of capital accumulation.

Too sleepy to drive : self-perception and regulation of driving when sleepy

Background: Sleepiness is a direct contributor to a substantial proportion of fatal and severe road cashes. A number of technological solutions designed to detect sleepiness have been developed, but self-awareness of increasing sleepiness remains a critical component in on-road strategies for mitigating this risk. In order to take appropriate action when sleepy, drivers’ perceptions of their level of sleepiness must be accurate. Aims: This study aimed to assess capacity to accurately identify sleepiness and self-regulate driving cessation during a validated driving simulator task. Participants: Participants comprised 26 young adult drivers (20-28 years). The drivers had open licenses but no other exclusion criteria where used. Methods: Participants woke at 5am, and took part in a laboratory-based hazard perception driving simulation, either at mid-morning or mid-afternoon. Established physiological measures (including EEG) and subjective measures (sleepiness ratings) previously found sensitive to changes in sleepiness levels were utilised. Participants were instructed to ‘drive’ until they believed that sleepiness had impaired their ability to drive safely. They were then offered a nap opportunity. Results: The mean duration of the drive before cessation was 39 minutes (±18 minutes). Almost all (23/26) of the participants then achieved sleep during the nap opportunity. These data suggest that the participants’ perceptions of sleepiness were specific. However, EEG data from a number of participants suggested very high levels of sleepiness prior to driving cessation, suggesting poor sensitivity. Conclusions: Participants reported high levels of sleepiness while driving after very moderate sleep restriction. They were able to identify increasing sleepiness during the test period, could decide to cease driving and in most cases were sufficiently sleepy to achieve sleep during the daytime session. However, the levels of sleepiness achieved prior to driving cessation suggest poor accuracy in self-perception and regulation. This presents practical issues for the implementation of fatigue and sleep-related strategies to improve driver safety.

Loss to assets : production of power from speed breaker

In this work, prospect and feasibility of power generation by using speed breakers has been investigated. In this project a mechanism to generate power by converting the potential energy generated by a vehicle going up on a speed breaker into kinetic energy. This arrangement is made one rotation as soon as the vehicle moves over the speed breaker and has been increased using gears. After the production electricity, a storing unit has been used to hoard the generated electricity during the day and will be used during the night. Two prototypes have made using rack and pinion gear, spur gear, springs and generator .From which a considerable amount of energy is obtained. Nonetheless the cost of the prototype was inexpensive which proves the feasibility of this project and the idea can be applied on heavy traffic roads. Further investigation is being carried on to introduce the technology for practical approach.

Developing guidelines for intervention to reduce risk of low-speed vehicle run-overs of young children

In Australia, research suggests that up to one quarter of child pedestrian hospitalisations result from driveway run-over incidents (Pinkney et al., 2006). In Queensland, these numbers equate to an average of four child fatalities and 81 children presenting at hospital emergency departments every year (The Commission for Children, Young People and Child Guardian). National comparison shows that these numbers represent a slightly higher per capita rate (23.5% of all deaths). To address this issue, the current research was undertaken with the aim to develop an educative intervention based on data collected from parents and caregivers of young children. Thus, the current project did not seek to use available intervention or educational material, but to develop a new evidence-based intervention specifically targeting driveway run-overs involving young children. To this end, general behavioural and environmental changes that caregivers had undertaken in order to reduce the risk of injury to any child in their care were investigated. Broadly, the first part of this report sought to: • develop a conceptual model of established domestic safety behaviours, and to investigate whether this model could be successfully applied to the driveway setting; • explore and compare sources of knowledge regarding domestic and driveway child safety; and • examine the theoretical implications of current domestic and driveway related behaviour and knowledge among caregivers. The aim of the second part of this research was to develop and test the efficacy of an intervention based on the findings in the first part of the research project. Specifically, it sought to: • develop an educational driveway intervention that is based on current safety behaviours in the domestic setting and informed by existing knowledge of driveway safety and behaviour change theory; and • evaluate its efficacy in a sample of parents and caregivers.