Unique residues involved in activation of the multitasking protease/chaperone HtrA from Chlamydia trachomatis

DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly.

School-community engagement : a critical approach to involving young people in an urban planning project

This study examines the participation of a group of high school students in designing a Heritage Journey as part of an urban redevelopment project in their community. School-community engagement offers young people an opportunity to engage in community life and influence decisions that affect them. Forging links between community and school is becoming more important for teachers as they attempt to create new authentic learning opportunities for young people within a changing world. Increasingly, researchers and urban planners are including children and young people as active decision makers and participants in community engagement projects. However, models of participation tend to be adult-focussed, conceive participation in terms of low to high graduated levels and lack a clearly articulated theoretical basis. The research problem in this study focuses on investigating whether the inclusion of young people in school-community engagement results in value adding to urban planning and is an example of genuine participation. The aim of the study is to provide a theoretically informed, empirically rich understanding of the inclusion of young people in a community engagement strategy for an urban planning project. Theories of space developed by Henri Lefebvre and Edward Soja are drawn upon for understanding how space is understood, used, and redeveloped by the students and other stakeholders. The study also draws on David Harvey’s notion of utopia and space to consider the imaginative possibilities of the students’ designs and ideas. The study uses a participatory research approach and documents the opportunities and challenges of this methodology. The thesis argues that school-community engagement within a "Thirdspace" offers many new opportunities for the emergence of authentic learning situations. Key findings from the study show young people’s participation in an urban planning project can achieve successful results when young people are given opportunities for full participation in decision-making processes; multiple pathways for active engagement are incorporated into the research design; opportunities for mentoring are provided; realistic timelines are communicated to all stakeholders and the needs and social practices of the local community are acknowledged. A new spatial model of community engagement is proposed as an outcome of the study. Unlike previous models of participation, this model demonstrates how exclusion and inclusion can be conceived visually, and may prove effective for conceptualising future community engagement projects that involve young people.

The increased popularity of mopeds and motor scooters : exploring usage patterns and safety outcomes

Increased use of powered two-wheelers (PTWs) often underlies increases in the number of reported crashes, promoting research into PTW safety. PTW riders are overrepresented in crash and injury statistics relative to exposure and, as such, are considered vulnerable road users. PTW use has increased substantially over the last decade in many developed countries. One such country is Australia, where moped and scooter use has increased at a faster rate than motorcycle use in recent years. Increased moped use is particularly evident in the State of Queensland which is one of four Australian jurisdictions where moped riding is permitted for car licence holders and a motorcycle licence is not required. A moped is commonly a small motor scooter and is limited to a maximum design speed of 50 km/h and a maximum engine cylinder capacity of 50 cubic centimetres. Scooters exceeding either of these specifications are classed as motorcycles in all Australian jurisdictions. While an extensive body of knowledge exists on motorcycle safety, some of which is relevant to moped and scooter safety, the latter PTW types have received comparatively little focused research attention. Much of the research on moped safety to date has been conducted in Europe where they have been popular since the mid 20th century, while some studies have also been conducted in the United States. This research is of limited relevance to Australia due to socio-cultural, economic, regulatory and environmental differences. Moreover, while some studies have compared motorcycles to mopeds in terms of safety, no research to date has specifically examined the differences and similarities between mopeds and larger scooters, or between larger scooters and motorcycles. To address the need for a better understanding of moped and scooter use and safety, the current program of research involved three complementary studies designed to achieve the following aims: (1) develop better knowledge and understanding of moped and scooter usage trends and patterns; and (2) determine the factors leading to differences in moped, scooter and motorcycle safety. Study 1 involved six-monthly observations of PTW types in inner city parking areas of Queensland’s capital city, Brisbane, to monitor and quantify the types of PTW in use over a two year period. Study 2 involved an analysis of Queensland PTW crash and registration data, primarily comparing the police-reported crash involvement of mopeds, scooters and motorcycles over a five year period (N = 7,347). Study 3 employed both qualitative and quantitative methods to examine moped and scooter usage in two components: (a) four focus group discussions with Brisbane-based Queensland moped and scooter riders (N = 23); and (b) a state-wide survey of Queensland moped and scooter riders (N = 192). Study 1 found that of the PTW types parked in inner city Brisbane over the study period (N = 2,642), more than one third (36.1%) were mopeds or larger scooters. The number of PTWs observed increased at each six-monthly phase, but there were no significant changes in the proportions of PTW types observed across study phases. There were no significant differences in the proportions or numbers of PTW type observed by season. Study 2 revealed some important differences between mopeds, scooters and motorcycles in terms of safety and usage through analysis of crash and registration data. All Queensland PTW registrations doubled between 2001 and 2009, but there was an almost fifteen-fold increase in moped registrations. Mopeds subsequently increased as a proportion of Queensland registered PTWs from 1.2 percent to 8.8 percent over this nine year period. Moped and scooter crashes increased at a faster rate than motorcycle crashes over the five year study period from July 2003 to June 2008, reflecting their relatively greater increased usage. Crash rates per 10,000 registrations for the study period were only slightly higher for mopeds (133.4) than for motorcycles and scooters combined (124.8), but estimated crash rates per million vehicle kilometres travelled were higher for mopeds (6.3) than motorcycles and scooters (1.7). While the number of crashes increased for each PTW type over the study period, the rate of crashes per 10,000 registrations declined by 40 percent for mopeds compared with 22 percent for motorcycles and scooters combined. Moped and scooter crashes were generally less severe than motorcycle crashes and this was related to the particular crash characteristics of the PTW types rather than to the PTW types themselves. Compared to motorcycle and moped crashes, scooter crashes were less likely to be single vehicle crashes, to involve a speeding or impaired rider, to involve poor road conditions, or to be attributed to rider error. Scooter and moped crashes were more likely than motorcycle crashes to occur on weekdays, in lower speed zones and at intersections. Scooter riders were older on average (39) than moped (32) and motorcycle (35) riders, while moped riders were more likely to be female (36%) than scooter (22%) or motorcycle riders (7%). The licence characteristics of scooter and motorcycle riders were similar, with moped riders more likely to be licensed outside of Queensland and less likely to hold a full or open licence. The PTW type could not be identified in 15 percent of all cases, indicating a need for more complete recording of vehicle details in the registration data. The focus groups in Study 3a and the survey in Study 3b suggested that moped and scooter riders are a heterogeneous population in terms of demographic characteristics, riding experience, and knowledge and attitudes regarding safety and risk. The self-reported crash involvement of Study 3b respondents suggests that most moped and scooter crashes result in no injury or minor injury and are not reported to police. Study 3 provided some explanation for differences observed in Study 2 between mopeds and scooters in terms of crash involvement. On the whole, scooter riders were older, more experienced, more likely to have undertaken rider training and to value rider training programs. Scooter riders were also more likely to use protective clothing and to seek out safety-related information. This research has some important practical implications regarding moped and scooter use and safety. While mopeds and scooters are generally similar in terms of usage, and their usage has increased, scooter riders appear to be safer than moped riders due to some combination of superior skills and safer riding behaviour. It is reasonable to expect that mopeds and scooters will remain popular in Queensland in future and that their usage may further increase, along with that of motorcycles. Future policy and planning should consider potential options for encouraging moped riders to acquire better riding skills and greater safety awareness. While rider training and licensing appears an obvious potential countermeasure, the effectiveness of rider training has not been established and other options should also be strongly considered. Such options might include rider education and safety promotion, while interventions could also target other road users and urban infrastructure. Future research is warranted in regard to moped and scooter safety, particularly where the use of those PTWs has increased substantially from low levels. Research could address areas such as rider training and licensing (including program evaluations), the need for more detailed and reliable data (particularly crash and exposure data), protective clothing use, risks associated with lane splitting and filtering, and tourist use of mopeds. Some of this research would likely be relevant to motorcycle use and safety, as well as that of mopeds and scooters.

An exploratory study of ethical dilemmas faced by academic leaders in three Australian universities

Being an academic in universities today is characterised by change and increasing complexity in response to a multitude of factors impacting on the university sector. Among the consequences of such changes are that many academics, and academic leaders in particular, are subjected to both increasing stress and scrutiny in many of the decisions they make. Some of these decisions require critical choices that involve contestation of values (including personal, professional, institutional, and community), resulting in ethical dilemmas for the decisionmakers. This article reports on an exploratory study into ethical dilemmas faced by middle-level academic leaders, drawing on the results of an on-line survey distributed to relevant academics in three universities in Australia. Here, middle-level academic leaders are defined as those holding course coordination roles, locating them between senior university staff and other academics on the one hand, and students on the other hand. As a consequence, these diverse groups of staff and students potentially have an array of conflicting interests in, and expectations on, middle-level academics’ decision-making processes. The findings of the study are clear: ethical dilemmas are evident, and commonly so, for many middle-level academic leaders. While exploratory in nature, the findings of this study suggest that much more attention to ethics and ethical dilemmas is needed in our universities.

Observations on catalysis by hammerhead ribozymes are consistent with a two-divalent-metal-ion mechanism

Significant cleavage by hammerhead ribozymes requires activation by divalent metal ions. Several models have been proposed to account for the influence of metal ions on hammerhead activity. A number of recent papers have presented data that have been interpreted as supporting a one-metal-hydroxide-ion mechanism. In addition, a solvent deuterium isotope effect has been taken as evidence against a proton transfer in the rate-limiting step of the cleavage reaction. We propose that these data are more easily explained by a two-metal-ion mechanism that does not involve a metal hydroxide, but does involve a proton transfer in the rate-limiting step.

Orthopedic bone plates : evolution in structure implementation technique and biomaterial

With many important developments over the last century, nowadays orthopedic bone plate now excels over other types of internal fixators in bone fracture fixation. The developments involve the design, material and implementation techniques of the plates. This paper aims to review the evolution in implementation technique and biomaterial of the orthopedic bone plates. Plates were initially used to fix the underlying bones firmly. Accordingly, Compression plate (CP), Dynamic compression plate (DCP), Limited contact dynamic compression plate (LC-DCP) and Point contact fixator (PC-Fix) were developed. Later, the implementation approach was changed to locking, and the Less Invasive Stabilization System (LISS) plate was introduced as a result. Finally, a combination of both of these approaches has been used by introducing the Locking Compression Plate (LCP). Currently, precontoured LCPs are mainly used for bone fracture fixation. In parallel with structure and implementation techniques, numerous advances have occurred in biomaterials of the plates. Titanium and stainless steel alloys are now the most common biomaterials in production of orthopedic bone plates. However, regarding the biocompatibility, bioactivity and biodegradability characteristics of Mg alloys, Ta alloys, SMAs, carbon fiber composites and bioceramics, these materials are considered as potentially suitable for plates. However, due to poor mechanical properties, they have very limited applications. Therefore, further studies are required in future to solve these problems and make them feasible for heavy-duty bone plates.

Hydrogen-bonding in cyclic imides and amide carboxylic acid derivatives from the facile reaction of cis-cyclohexane-1,2-carboxylic anhydride with o- and p-anisidine and m- and p-aminobenzoic acids

The structures of the open chain amide carboxylic acid rac-cis-[2-(2-methoxyphenyl)carbamoyl]cyclohexane-1-carboxylic acid, C15H19NO4, (I) and the cyclic imides rac-cis-2-(4-methoxyphenyl)-3a,4,5,6,7,7-hexahydroisoindole-1,3-dione,C15H17NO3, (II), chiral cis-2-(3-carboxyphenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione, C15H15NO4,(III) and rac-cis-2-(4-carboxyphenyl)- 3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione monohydrate, C15H15NO4. H2O) (IV), are reported. In the amide acid (I), the phenylcarbamoyl group is essentially planar [maximum deviation from the least-squares plane = 0.060(1)Ang. for the amide O atom], the molecules form discrete centrosymmetric dimers through intermolecular cyclic carboxy-carboxy O-H...O hydrogen-bonding interactions [graph set notation R2/2(8)]. The cyclic imides (II)--(IV) are conformationally similar, with comparable phenyl ring rotations about the imide N-C(aromatic) bond [dihedral angles between the benzene and isoindole rings = 51.55(7)deg. in (II), 59.22(12)deg. in (III) and 51.99(14)deg. in (IV). Unlike (II) in which only weak intermolecular C-H...O(imide) hydrogen bonding is present, the crystal packing of imides (III) and (IV) shows strong intermolecular carboxylic acid O-H...O hydrogen-bonding associations. With (III), these involve imide O-atom acceptors, giving one-dimensional zigzag chains [graph set C(9)], while with the monohydrate (IV), the hydrogen bond involves the partially disordered water molecule which also bridges molecules through both imide and carboxyl O-atom acceptors in a cyclic R4/4(12) association, giving a two-dimensional sheet structure. The structures reported here expand the structural data base for compounds of this series formed from the facile reaction of cis-cyclohexane-1,2-dicarboxylic anhydride with substituted anilines, in which there is a much larger incidence of cyclic imides compared to amide carboxylic acids.

Does charity begin and end at home for tax exemptions?

Charitable organisations have remained exempt from income tax in Australia since the first comprehensive state income tax legislation in 18841 through to the current Income Tax Assessment Act 1977. The charitable exemption was also part of the English income tax legislation from its inception in 1799. The Federal Treasurer has released exposure draft legislation which seeks to remove taxation exemptions from some tax exempt organisations that perform any of their activities outside Australia or make trust distributions overseas. The proposed legislation is in response to alleged tax avoidance arrangements which involve tax exempt organisations and charitable trusts. The paper begins by describing the current charity tax exemption provisions under the Income Tax Assessment Act (ITAA). It then turns to tracing the background policy history of the amendments which appear to be at odds with the form and intent of the proposed provisions. The proposed amendments and their practical consequences are then closely scrutinised and found wanting in a number of respects. Alternative strategies are suggested to arrive at an equitable solution to the avoidance mischief.

Family law issues and schools : guidance for Australian educators

A substantial number of Australian children are now living in separated families, with many moving between their parents’ homes. This has led to educators being confronted with an increasing number of family law issues. This article discusses the key aspects of family law that involve children. It highlights the need for schools to be aware of all family law orders that relate to children in their care, including family court, domestic violence and child protection orders. It also provides guidance in relation to how schools can adopt child focused approaches in some common scenarios, where parents are in dispute. In particular, we will recommend that educators take a child-focused approach, consistent with the principal provision of the Family Law Act 1975 (Cth) that ‘the best interests of the child’ be the paramount consideration. We will highlight how this contrasts starkly with what can be described as a ‘parental rights’ interpretation, which has unfortunately been taken by some since the 2006 amendments to the Family Law Act, and is, in our view, directly at odds with the intention of the legislation.

Does the protection of vulnerable children require a system of mandatory reporting of abuse and neglect? [An issues paper for the New Zealand Government Green Paper for vulnerable children]

In this Issues Paper, I raise some key points relevant for any government which is considering its child protection and family welfare policy. In particular, I will raise questions about whether a form of legislative reporting duty is required, and if so, what consequences this has for child protection. The context of child maltreatment - and each form of maltreatment: physical abuse, sexual abuse, psychological or emotional abuse, and neglect - is extremely complex, and the overarching question of how to deal with these phenomena involve challenging normative, economic and practical questions. There are no easy or perfect solutions. Nor, often, is there the amount and quality of evidence available on which public policy approaches should be devised. However, from the best evidence about the history of this context, from research conducted in this field, and from the best evidence available about the nature, incidence and effects of different subtypes of maltreatment, some observations can be made which may help to inform deliberations. I outline 10 key issues related to mandatory reporting legislation while being mindful of the New Zealand context. My view, based on both research evidence and a concern to protect and promote children’s interests, and society’s interests, is that reporting laws in some form are necessary and can contribute substantially to child protection and enhancing family and community health and wellbeing. However, they are only one necessary part of a sound child protection system, being a method of tertiary and secondary prevention, and primary prevention efforts must also be prioritised. Moreover, it is essential that if a legislative reporting duty is enacted, it must be designed carefully and implemented soundly, and it must be integrated within a properly resourced child protection and family welfare system.

Vertical Inhibition of the PI3K/Akt/mTOR Pathway for the Treatment of Osteoarthritis

Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome.

Neuromuscular imbalances in the track sprinter

Athletic coaching can involve observation of a motor control task and then proposing guidance to an athlete about how the task performance can be developed. Coaches can identify the technique elements that seem to hinder performance and then provide instruction. Recently, a variety of training methods were proposed to enhance sprint performance, however a number of authors have identified these methods as characterised by low scientific evaluation or support (Brown & Vescovi, 2012; Jones, Bezodis, & Thompson, 2009). This article will outline a scientifically robust neuromuscular theory underlying poor movement techniques that may be visible when coaches observe sprint performance. The goal of this article is to inform the sprint coach of a method to identify and correct suboptimal biomechanics to enhance athletic performance.

Dirichlet process mixture models for unsupervised clustering of symptoms in Parkinson's disease

In this paper, the goal of identifying disease subgroups based on differences in observed symptom profile is considered. Commonly referred to as phenotype identification, solutions to this task often involve the application of unsupervised clustering techniques. In this paper, we investigate the application of a Dirichlet Process mixture (DPM) model for this task. This model is defined by the placement of the Dirichlet Process (DP) on the unknown components of a mixture model, allowing for the expression of uncertainty about the partitioning of observed data into homogeneous subgroups. To exemplify this approach, an application to phenotype identification in Parkinson’s disease (PD) is considered, with symptom profiles collected using the Unified Parkinson’s Disease Rating Scale (UPDRS). Clustering, Dirichlet Process mixture, Parkinson’s disease, UPDRS.

Nonprofits and the GST : don't sign anything until you've read the fine print, (if you can find it to read!)

On 13 August, 1997 Prime Minister Mr Howard announced five principles as a foundation for a Tax Reform Package to revitalise the Australian economy. They were that: 1. there should be no overall increase in the overall tax burden; 2. any new taxation system should involve major reductions in personal income tax with special regard to the taxation treatment of families; 3. consideration should be given to a broad-based indirect tax to replace some or all of the existing indirect taxes; 4. there would be appropriate compensation for those deserving of special consideration; and 5. reform of Commonwealth-State financial relations must be addressed...

Respiratory health effects of diesel particulate matter

Particulate matter (PM) emissions involve a complex mixture of solid and liquid particles suspended in a gas, where it is noted that PM emissions from diesel engines are a major contributor to the ambient air pollution problem. Whilst epidemiological studies have shown a link between increased ambient PM emissions and respiratory morbidity and mortality, studies of this design are not able to identify the PM constituents responsible for driving adverse respiratory health effects. This review explores in detail the physico-chemical properties of diesel particulate matter (DPM), and identifies the constituents of this pollution source that are responsible for the development of respiratory disease. In particular, this review shows that the DPM surface area and adsorbed organic compounds play a significant role in manifesting chemical and cellular processes that if sustained can lead to the development of adverse respiratory health effects. The mechanisms of injury involved included: inflammation, innate and acquired immunity, and oxidative stress. Understanding the mechanisms of lung injury from DPM will enhance efforts to protect at-risk individuals from the harmful respiratory effects of air pollutants.