The extraordinary radio galaxy MRC B1221-423: probing deeper at radio and optical wavelengths

We present optical spectra and high-resolution multi-wavelength radio observations of the compact steep-spectrum radio source MRC B1221-423 (z=0.1706). MRC B1221-423 is a very young (~10^5 yr), powerful radio source which is undergoing a tidal interaction with a companion galaxy. We find strong evidence of interaction between the AGN and its environment. The radio morphology is highly distorted, showing a dramatic interaction between the radio jet and the host galaxy, with the jet being turned almost back on itself. H I observations show strong absorption against the nucleus at an infall velocity of ~250 km/s compared to the stellar velocity, as well as a second, broader component which may represent gas falling into the nucleus. Optical spectra show that star formation is taking place across the whole system. Broad optical emission lines in the nucleus show evidence of outflow. Our observations confirm that MRC B1221-423 is a young radio source in a gas-rich nuclear environment, and that there was a time delay of a few x 100 Myr between the onset of star formation and the triggering of the AGN.Comment: 15 pages, 13 figures, to appear in MNRA

Home-based exercise for people living with frailty and chronic kidney disease: A mixed-methods pilot randomised controlled trial

Background: Frailty is associated with adverse health outcomes in people with chronic kidney disease (CKD). Evidence supporting targeted interventions is needed. This pilot randomised controlled trial (RCT) aimed to inform the design of a definitive RCT evaluating the effectiveness of a home-based exercise intervention for pre-frail and frail older adults with CKD. Methods: Participants were recruited from nephrology outpatient clinics to this two-arm parallel group mixed-methods pilot RCT. Inclusion criteria were: ≥65 years old; CKD G3b-5; and Clinical Frailty Scale score ≥4. Participants categorised as pre-frail or frail using the Frailty Phenotype were randomised to a 12-week progressive multi-component home-based exercise programme or usual care. Primary outcome measures included eligibility, recruitment, adherence, outcome measure completion and participant attrition rate. Semi-structured interviews were conducted with participants to explore trial and intervention acceptability. Results: Six hundred and sixty-five patients had an eligibility assessment with 217 (33%; 95% CI 29, 36) eligible. Thirty-five (16%; 95% CI 12, 22) participants were recruited. Six were categorised as robust and withdrawn prior to randomisation. Fifteen participants were randomised to exercise and 14 to usual care. Eleven (73%; 95% CI 45, 91) participants completed ≥2 exercise sessions/week. Retained participants completed all outcome measures (n = 21; 100%; 95% CI 81, 100). Eight (28%; 95% CI 13, 47) participants were withdrawn. Fifteen participated in interviews. Decision to participate/withdraw was influenced by perceived risk of exercise worsening symptoms. Participant perceived benefits included improved fitness, balance, strength, well-being, energy levels and confidence. Conclusions: This pilot RCT demonstrates that progression to definitive RCT is possible provided recruitment and retention challenges are addressed. It has also provided preliminary evidence that home-based exercise may be beneficial for people living with frailty and CKD. Trial registration: ISRCTN87708989; https://clinicaltrials.gov/

G-protein-coupled inwardly rectifying potassium (GIRK) channel activation by the p75 neurotrophin receptor is required for amyloid beta toxicity

Alzheimer's disease is characterized by cognitive decline, neuronal degeneration, and the accumulation of amyloid-beta (Aβ). Although, the neurotoxic Aβ peptide is widely believed to trigger neuronal dysfunction and degeneration in Alzheimer's disease, the mechanism by which this occurs is poorly defined. Here we describe a novel, Aβ-triggered apoptotic pathway in which Aβ treatment leads to the upregulation of G-protein activated inwardly rectifying potassium (GIRK/Kir3) channels, causing potassium efflux from neurons and Aβ-mediated apoptosis. Although, GIRK channel activity is required for Aβ-induced neuronal degeneration, we show that it is not sufficient, with coincident signaling by the p75 neurotrophin receptor (p75) also required for potassium efflux and cell death. Our results identify a novel role for GIRK channels in mediating apoptosis, and provide a previously missing mechanistic link between the excitotoxicity of Aβ and its ability to trigger cell death pathways, such as that mediated by p75. We propose that this death-signaling pathway contributes to the dysfunction of neurons in Alzheimer's disease and is responsible for their eventual degeneration

Stability, reliability and performance of organic light-emitting diodes and photodetectors in optogenetic studies

Mapping neurons in the brain is important to understand the neuronal circuits involved in cognitive functions such as learning and memory formation. More importantly, understanding their dysfunction in neurological disorders and diseases could benefit patients that rely on better therapy interventions and techniques. To this aim, optogenetic tools, where light is used to control neuronal activity, and ultimately behavior, have revolutionized the field of neuroscience over the last 20 years. Current optogenetic approaches to investigate brain function involve the use of commercially available lasers and LEDs coupled to large implants, optical fibers or camera systems. Their use is usually associated with high cost, invasiveness and low spatial resolution. To address these limitations, organic electronic devices have been emerging as an alternative candidate for biocompatible, small-footprint, and high-resolution neural probes. In our own contribution to the field, we have demonstrated the successful detection of neuronal activity using organic photodetectors (OPDs) based on rubrene/C60, as well as direct optogenetic stimulation of neuronal activity using OLEDs based on Super Yellow. In this paper, we extend our previous work by demonstrating the stability and reliability of OPDs and OLEDs in optogenetics, and the effect of oxygen and encapsulation on the OPD/OLED performance. We also discuss the requirements for successful long-term neural recordings and determine the detection threshold for OPDs, (i.e. the required sensitivity to detect activity in a single neuron), as well as the minimum performance requirements in OLEDs to evoke neuronal activity.</p

Conceptualising, evaluating and reporting social resilience in vulnerable regional and remote communities facing climate change in tropical Queensland : marine and tropical sciences research facility transition project final report

Regional and remote communities in tropical Queensland are among Australia’s most vulnerable in the face of climate change. At the same time, these socially and economically vulnerable regions house some of Australia’s most significant biodiversity values. Past approaches to terrestrial biodiversity management have focused on tackling biophysical interventions through the use of biophysical knowledge. An equally important focus should be placed on building regional-scale community resilience if some of the worst biodiversity impacts of climate change are to be avoided or mitigated. Despite its critical need, more systemic or holistic approaches to natural resource management have been rarely trialed and tested in a structured way. Currently, most strategic interventions in improving regional community resilience are ad hoc, not theory-based and short term. Past planning approaches have not been durable, nor have they been well informed by clear indicators. Research into indicators for community resilience has been poorly integrated within adaptive planning and management cycles. This project has aimed to resolve this problem by: * Reviewing the community and social resilience and adaptive planning literature to reconceptualise an improved framework for applying community resilience concepts; * Harvesting and extending work undertaken in MTSRF Phase 1 to identifying the learnings emerging from past MTSRF research; * Distilling these findings to identify new theoretical and practical approaches to the application of community resilience in natural resource use and management; * Reconsidering the potential interplay between a region’s biophysical and social planning processes, with a focus on exploring spatial tools to communicate climate change risk and its consequent environmental, economic and social impacts, and; * Trialling new approaches to indicator development and adaptive planning to improve community resilience, using a sub-regional pilot in the Wet Tropics. In doing so, we also looked at ways to improve the use and application of relevant spatial information. Our theoretical review drew upon the community development, psychology and emergency management literature to better frame the concept of community resilience relative to aligned concepts of social resilience, vulnerability and adaptive capacity. Firstly, we consider community resilience as a concept that can be considered at a range of scales (e.g. regional, locality, communities of interest, etc.). We also consider that overall resilience at higher scales will be influenced by resilience levels at lesser scales (inclusive of the resilience of constituent institutions, families and individuals). We illustrate that, at any scale, resilience and vulnerability are not necessarily polar opposites, and that some understanding of vulnerability is important in determining resilience. We position social resilience (a concept focused on the social characteristics of communities and individuals) as an important attribute of community resilience, but one that needs to be considered alongside economic, natural resource, capacity-based and governance attributes. The findings from the review of theory and MTSRF Phase 1 projects were synthesized and refined by the wider project team. Five predominant themes were distilled from this literature, research review and an expert analysis. They include the findings that: 1. Indicators have most value within an integrated and adaptive planning context, requiring an active co-research relationship between community resilience planners, managers and researchers if real change is to be secured; 2. Indicators of community resilience form the basis for planning for social assets and the resilience of social assets is directly related the longer term resilience of natural assets. This encourages and indeed requires the explicit development and integration of social planning within a broader natural resource planning and management framework; 3. Past indicator research and application has not provided a broad picture of the key attributes of community resilience and there have been many attempts to elicit lists of “perfect” indicators that may never be useful within the time and resource limitations of real world regional planning and management. We consider that modeling resilience for proactive planning and prediction purposes requires the consideration of simple but integrated clusters of attributes; 4. Depending on time and resources available for planning and management, the combined use of well suited indicators and/or other lesser “lines of evidence” is more flexible than the pursuit of perfect indicators, and that; 5. Index-based, collaborative and participatory approaches need to be applied to the development, refinement and reporting of indicators over longer time frames. We trialed the practical application of these concepts via the establishment of a collaborative regional alliance of planners and managers involved in the development of climate change adaptation strategies across tropical Queensland (the Gulf, Wet Tropics, Cape York and Torres Strait sub-regions). A focus on the Wet Tropics as a pilot sub-region enabled other Far North Queensland sub-region’s to participate and explore the potential extension of this approach. The pilot activities included: * Further exploring ways to innovatively communicate the region’s likely climate change scenarios and possible environmental, economic and social impacts. We particularly looked at using spatial tools to overlay climate change risks to geographic communities and social vulnerabilities within those communities; * Developing a cohesive first pass of a State of the Region-style approach to reporting community resilience, inclusive of regional economic viability, community vitality, capacitybased and governance attributes. This framework integrated a literature review, expert (academic and community) and alliance-based contributions; and * Early consideration of critical strategies that need to be included in unfolding regional planning activities with Far North Queensland. The pilot assessment finds that rural, indigenous and some urban populations in the Wet Tropics are highly vulnerable and sensitive to climate change and may require substantial support to adapt and become more resilient. This assessment finds that under current conditions (i.e. if significant adaptation actions are not taken) the Wet Tropics as a whole may be seriously impacted by the most significant features of climate change and extreme climatic events. Without early and substantive action, this could result in declining social and economic wellbeing and natural resource health. Of the four attributes we consider important to understanding community resilience, the Wet Tropics region is particularly vulnerable in two areas; specifically its economic vitality and knowledge, aspirations and capacity. The third and fourth attributes, community vitality and institutional governance are relatively resilient but are vulnerable in some key respects. In regard to all four of these attributes, however, there is some emerging capacity to manage the possible shocks that may be associated with the impacts of climate change and extreme climatic events. This capacity needs to be carefully fostered and further developed to achieve broader community resilience outcomes. There is an immediate need to build individual, household, community and sectoral resilience across all four attribute groups to enable populations and communities in the Wet Tropics region to adapt in the face of climate change. Preliminary strategies of importance to improve regional community resilience have been identified. These emerging strategies also have been integrated into the emerging Regional Development Australia Roadmap, and this will ensure that effective implementation will be progressed and coordinated. They will also inform emerging strategy development to secure implementation of the FNQ 2031 Regional Plan. Of most significance in our view, this project has taken a co-research approach from the outset with explicit and direct importance and influence within the region’s formal planning and management arrangements. As such, the research: * Now forms the foundations of the first attempt at “Social Asset” planning within the Wet Tropics Regional NRM Plan review; * Is assisting Local government at regional scale to consider aspects of climate change adaptation in emerging planning scheme/community planning processes; * Has partnered the State government (via the Department of Infrastructure and Planning and Regional Managers Coordination Network Chair) in progressing the Climate Change adaptation agenda set down within the FNQ 2031 Regional Plan; * Is informing new approaches to report on community resilience within the GBRMPA Outlook reporting framework; and * Now forms the foundation for the region’s wider climate change adaptation priorities in the Regional Roadmap developed by Regional Development Australia. Through the auspices of Regional Development Australia, the outcomes of the research will now inform emerging negotiations concerning a wider package of climate change adaptation priorities with State and Federal governments. Next stage research priorities are also being developed to enable an ongoing alliance between researchers and the region’s climate change response

G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channel Activation by the p75 Neurotrophin Receptor Is Required for Amyloid β Toxicity

Alzheimer's disease is characterized by cognitive decline, neuronal degeneration, and the accumulation of amyloid-beta (Aβ). Although, the neurotoxic Aβ peptide is widely believed to trigger neuronal dysfunction and degeneration in Alzheimer's disease, the mechanism by which this occurs is poorly defined. Here we describe a novel, Aβ-triggered apoptotic pathway in which Aβ treatment leads to the upregulation of G-protein activated inwardly rectifying potassium (GIRK/Kir3) channels, causing potassium efflux from neurons and Aβ-mediated apoptosis. Although, GIRK channel activity is required for Aβ-induced neuronal degeneration, we show that it is not sufficient, with coincident signaling by the p75 neurotrophin receptor (p75NTR) also required for potassium efflux and cell death. Our results identify a novel role for GIRK channels in mediating apoptosis, and provide a previously missing mechanistic link between the excitotoxicity of Aβ and its ability to trigger cell death pathways, such as that mediated by p75NTR. We propose that this death-signaling pathway contributes to the dysfunction of neurons in Alzheimer's disease and is responsible for their eventual degeneration

1,25-Dihydroxyvitamin D modulates L-type voltage-gated calcium channels in a subset of neurons in the developing mouse prefrontal cortex

Schizophrenia has been associated with a range of genetic and environmental risk factors. Here we explored a link between two risk factors that converge on a shared neurobiological pathway. Recent genome-wide association studies (GWAS) have identified risk variants in genes that code for L-type voltage-gated calcium channels (L-VGCCs), while epidemiological studies have found an increased risk of schizophrenia in those with neonatal vitamin D deficiency. The active form of vitamin D (1,25(OH)D) is a secosteroid that rapidly modulates L-VGCCs via non-genomic mechanisms in a range of peripheral tissues, though its non-genomic effects within the brain remain largely unexplored. Here we used calcium imaging, electrophysiology and molecular biology to determine whether 1,25(OH)D non-genomically modulated L-VGCCs in the developing prefrontal cortex, a region widely implicated in schizophrenia pathophysiology. Wide-field Ca imaging revealed that physiological concentrations of 1,25(OH)D rapidly enhanced activity-dependent somatic Ca levels in a small subset of neurons in the developing PFC, termed vitamin D-responsive neurons (VDRNs). Somatic nucleated patch recordings revealed a rapid, 1,25(OH)D-evoked increase in high-voltage-activated (HVA) Ca currents. Enhanced activity-dependent Ca levels were mediated by L-VGCC but not associated with any changes to Cacna1c (L-VGCC pore-forming subunit) mRNA expression. Since L-VGCC activity is critical to healthy neurodevelopment, these data suggest that suboptimal concentrations of 1,25(OH)D could alter brain maturation through modulation of L-VGCC signalling and as such may provide a parsimonious link between epidemiologic and genetic risk factors for schizophrenia

High-dose Mycobacterium tuberculosis aerosol challenge cannot overcome BCG-induced protection in Chinese origin cynomolgus macaques; implications of natural resistance for vaccine evaluation

Abstract This study describes the use of cynomolgus macaques of Chinese origin (CCM) to evaluate the efficacy and immunogenicity of the BCG vaccine against high dose aerosol Mycobacterium tuberculosis challenge. Progressive disease developed in three of the unvaccinated animals within 10 weeks of challenge, whereas all six vaccinated animals controlled disease for 26 weeks. Three unvaccinated animals limited disease progression, highlighting the intrinsic ability of this macaque species to control disease in comparison to macaques of other species and genotypes. Low levels of IFNγ were induced by BCG vaccination in CCM suggesting that IFNγ alone does not provide a sufficiently sensitive biomarker of vaccination in this model. An early response after challenge, together with the natural bias towards terminal effector memory T-cell populations and the contribution of monocytes appears to enhance the ability of CCM to naturally control infection. The high dose aerosol challenge model of CCM has value for examination of the host immune system to characterise control of infection which would influence future vaccine design. Although it may not be the preferred platform for the assessment of prophylactic vaccine candidates, the model could be well suited for testing post-exposure vaccination strategies and drug evaluation studies