19683 research outputs found
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Global analysis of endogenous protein disorder in cells
Disorder and flexibility in protein structures are essential for biological function but can also contribute to diseases, such as neurodegenerative disorders. However, characterizing protein folding on a proteome-wide scale within biological matrices remains challenging. Here we present a method using a bifunctional chemical probe, named TME, to capture in situ, enrich and quantify endogenous protein disorder in cells. TME exhibits a fluorescence turn-on effect upon selective conjugation with proteins with free cysteines in surface-exposed and flexible environments—a distinctive signature of protein disorder. Using an affinity-based proteomic approach, we identify both basal disordered proteins and those whose folding status changes under stress, with coverage to proteins even of low abundance. In lymphoblastoid cells from individuals with Parkinson’s disease and healthy controls, our TME-based strategy distinguishes the two groups more effectively than lysate profiling methods. High-throughput TME fluorescence and proteomics further reveal a universal cellular quality-control mechanism in which cells adapt to proteostatic stress by adopting aggregation-prone distributions and sequestering disordered proteins, as illustrated in Huntington’s disease cell models.</p
LGBTQA+ Mental Health and Suicidality: Australian Capital Territory Briefing Paper
Suicidality and mental ill-health are serious concerns that impact all parts of the population in Australia, although some are disproportionately affected. LGBTQA+ people are recognised in numerous Commonwealth, State and Territory mental health and suicide prevention strategies or action plans.However, LGBTQA+ people continue to face barriers to accessing affirming healthcare and, to-date, limited comprehensive data exists on the mental health and healthcare experiences of LGBTQA+ people. This briefing paper outlines findings from three major surveys of LGBTQA+ people and aims to:Highlight the extent and nature of mental ill-health and suicidality among LGBTQA+ young people and adults in Australian Capital Territory (ACT).Explore the factors that can put people at greater risk of suicide or mental ill-health, as well as those that reduce their risk of suicide.Examine mental health service engagement and preferences among LGBTQA+ people in ACT.Draw comparisons between experience of LGBTQA+ people in ACT compared to other jurisdictions in Australia, and where possible, comparisons between LGBTQA+ people in ACT to the general population using the latest data from the Australian Bureau of Statistics (ABS; 2022-2022).</p
‘Hot mic’ moment aside, the Albanese government’s Pacific policing deal is a masterstroke of diplomacy
“The geopolitical rivalry between China and Australia, the United States and their allies has been encroaching on all aspects of regional diplomacy, and Pacific leaders came into this meeting wanting to refocus the agenda.”</p
How does climate change impact people who use alcohol and other drugs? A scoping review of peer reviewed literature
Background: The world has experienced devastating extreme weather events, alongside slow-onset processes including increasing temperature means, that scientists agree are manifestations of human-induced climate change. Even with radical action to reduce greenhouse gas emissions, effects of climate change will become increasingly severe. Objectives: The aim of this review was to classify impacts of climate change for people who use alcohol and other drugs (AoD), as reflected in peer reviewed literature. Method: A scoping review was conducted to achieve this. Included studies involved a human population, a climate change related exposure, and an AoD outcome. Studies were published in English between 1998 and November 2023. Exposure events of interest included extreme heat, fires, storms, floods, droughts, and longer-term environmental changes. 8,204 studies were screened, with 82 included for data extraction and narrative analysis. Results: Most papers describe increased AoD use, with smaller numbers showing decreased or unchanged substance use. Some studies identify unplanned withdrawal, changed drug markets, disrupted service access, specific physiological vulnerabilities of AoD users to extreme heat, and compounding effects on mental health. We note the relative absence of peer reviewed studies investigating impacts of climate change on AoD use in low-and middle-income countries. Further, few studies consider impacts that occur because of long-term or gradual climatic shifts such as environmental changes that are detrimental to livelihoods. Conclusion: It is crucial to document effects of a changing climate on people who use AoD so that policy and services can meet future needs. We call for research to remedy gaps identified in this review.</p
Evaluation of effectiveness of bacteriophage purification methods
The use of bacteriophages for therapy has increased over the last decade. While there is need for clear regulatory pathways for bacteriophage approval for mainstream use in clinical practice, practitioners and patients have been able to access bacteriophage therapy under compassionate grounds and through magistral preparations. However, there is currently no standard for purifying these bacteriophages to ensure safety, and good manufacturing practice certification may not be achieved in these emergency uses. In this study, we employed an Interleukin Receptor Associated Kinase (IRAK) 3 knockout monocyte-based assay to evaluate the endotoxin removal efficacy of three common bacteriophage purification methods: Triton X-100 exposure, CsCl density gradient ultracentrifugation, and Pierce™ High-Capacity Endotoxin Removal Resin spin columns. In our experiments we tested these purification methods on three different bacteriophage morphotypes: siphovirus, podovirus and myovirus. We showed that the lowest endotoxin levels and immune responses were achieved when purifying bacteriophages with Triton-X treatment. The results from purifying with CsCl density gradient ultracentrifugation were comparable, and these were both significantly better than purification with Pierce™ High-Capacity Endotoxin Removal Resin spin columns. We also showed that Triton X-100 purification resulted in the lowest loss of bacteriophage titres. Finally, of the bacteriophages tested here, it did not appear that virus morphology affected efficacy of endotoxin removal.</p
From Emotional Labour to Affectual Bodies: Moving Towards an ‘Affective Ethnography’ of the Criminal Court Space
Participation in, and attendance at, court often positions people amid a charged emotional environment, where the evidence frequently involves distressing accounts and the stakes of decision-making are high. Research has explored the impact of this environment on various court protagonists. What this research has failed to consider in detail, however, are the ways in which such vectors of emotional reaction, containment and contagion interact and flow across the criminal court space: yielding affective environments in which emotion is not a commodity held (or denied) by one person, but a force that permeates and seeps into the spaces of justice. In this article, we set out the case for why such an understanding is necessary and instructive.</p
Accuracy of GNSS-Derived Acceleration Data for Dynamic Team Sport Movements: A Comparative Study of Smoothing Techniques
This study examined the impact of various smoothing techniques on acceleration data obtained from a Global Navigation Satellite System (GNSS) device during accelerating and decelerating movements, resembling those commonly observed in team sports. Eight participants performed six different accelerating and decelerating movements at different intensities and starting speeds for a total of 46 trials each. The movements were collected concurrently at 10 Hz using a GNSS device (Vector S7, Catapult Sports) at 100 Hz using a motion analysis system (Vicon). Acceleration data were smoothed using (I) a fourth-order Butterworth filter (cut-off frequencies ranging from raw to 4.9 Hz), (II) exponential smoothing (smoothing constant ranging from 0.1 to 0.9), and (III) moving average (sliding window ranging from 0.2 s to 2.0 s). To determine the ability of a GNSS to quantify acceleration, a variety of measurement indices of validity were obtained for each movement and each smoothing technique. The fourth-order Butterworth filter with a cut-off frequency of 2 Hz (mean bias 0.00 m·s−2, 95% LoA ± 1.55 m·s−2, RMSE 0.79 m·s−2) showed the strongest relationship with the Vicon data. These results indicate that this smoothing technique is more accurate than those currently used and accepted on GNSS devices in the sports science community.</p
Continuous improvement strategies towards energy transition: The importance of individual employees' entrepreneurial orientation and learning processes
No description supplied</p
Australia's Crimean War Imperial Russian Trophy Guns: How they have been both important military history objects and contested objects
No description supplied</p
Justice for institutional child abuse survivors: Comparing views from survivor and non-survivor led advocacy groups
Abstract:Background: How victims and survivors of non-recent institutional child abuse – and the advocacy groups that support them – conceptualise justice has become a central concern for policy makers designing redress schemes.Objectives: This study aimed to explore articulations of justice by two types of advocacy organisations in Australia – survivor and non-survivor led groups – by examining transcripts from public hearings of the Australian Royal Commission into Institutional Responses to Child Sexual Abuse.Participants and setting: Hearings held in 2015 for Case Study 25: Redress and Civil Litigation were analysed. The analysis focused on five survivor led groups and 13 non-survivor led groups.Methods: Using a framework adapted from Daly (2014, 2017), qualitative content and thematic analysis was used to analyse transcript data to identify "justice interests" and “survival needs”.Results: For survivor led groups, validation was the most frequently coded justice interest, while for the non-survivor led groups, the category of survival needs was the most frequently recorded element.Conclusions: Advocacy groups contribute highly valuable insights and perspectives to redress consultation and design processes. A key justice interest emphasised by survivor led groups was the need for public acknowledgement of how offending institutions wield power, both in the abuse of children and in the subsequent strategies employed to ensure survival of the institution and avoid justice processes. For non-survivor led groups, communicating their professional expertise about what victims and survivors need from a redress scheme was paramount.</p