19683 research outputs found
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Reduced PI3K(p110α) induces atrial myopathy, and PI3K-related lipids are dysregulated in athletes with atrial fibrillation
No full textBackground: Elucidating mechanisms underlying atrial myopathy, which predisposes individuals to atrial fibrillation (AF), will be critical for preventing/treating AF. In a serendipitous discovery, we identified atrial enlargement, fibrosis, and thrombi in mice with reduced phosphoinositide 3-kinase (PI3K) in cardiomyocytes. PI3K(p110α) is elevated in the heart with exercise and is critical for exercise-induced ventricular enlargement and protection, but the role in the atria was unknown. Physical inactivity and extreme endurance exercise can increase AF risk. Therefore, our objective was to investigate whether too little and/or too much PI3K alone induces cardiac pathology. Methods: New cardiomyocyte-specific transgenic mice with increased or decreased PI3K(p110α) activity were generated. Multi-omics was conducted in mouse atrial tissue, and lipidomics in human plasma. Results: Elevated PI3K led to an increase in heart size with preserved/enhanced function. Reduced PI3K led to atrial dysfunction, fibrosis, arrhythmia, increased susceptibility to atrial enlargement and thrombi, and dysregulation of monosialodihexosylganglioside (GM3), a lipid that regulates insulin-like growth factor-1 (IGF1)–PI3K signaling. Proteomic profiling identified distinct signatures and signaling networks across atria with varying degrees of dysfunction, enlargement, and thrombi, including commonalities with the human AF proteome. PI3K-related lipids were dysregulated in plasma from athletes with AF. Conclusion: PI3K(p110α) is a critical regulator of atrial biology and function in mice. This work provides a proteomic resource of candidates for further validation as potential new drug targets and biomarkers for atrial myopathy. Further investigation of PI3K-related lipids as markers for identifying individuals at risk of AF is warranted. Dysregulation of PI3K may contribute to the association between increased cardiac risk with physical inactivity and extreme endurance exercise.</p
Deep_Time_Detectives_3D_models_stratigraphic_unit_2
No full textThese files are the 3D models and printing instructions for you to use for stratigraphic unit 2 of the simulated excavation. Details of these models can be found in the Teacher Resource Booklet.All models are publicly available under a CC BY 4.0 licence. Details of the provenance for each model is provided in the excel spreadsheet included in this folder.</p
Deep_Time_Detectives_3D_models_stratigraphic_unit_4
No full textThese files are the 3D models and printing instructions for you to use for stratigraphic unit 4 of the simulated excavation. Details of these models can be found in the Teacher Resource Booklet.All models are publicly available under a CC BY 4.0 licence. Details of the provenance for each model is provided in the excel spreadsheet included in this folder.</p
A First Nations Perspective Stories of Nanda Resilience as Told by Elders
No full textThis book is an extrapolation of the research I conducted for my doctoral thesis about my people’s struggle to come to terms with native title claim processes, in which we are required to prove our connection to land, culture and kin.https://www.routledge.com/A-First-Nations-Perspective-Stories-of-Nanda-Resilience-as-Told-by-Elders/Kelly/p/book/ 9781032882451?srsltid=AfmBOooApMxjELrB2E0Es2S3cvgRvaD2pQU5eorv1zceCm9lWGEWo1Rn</p
Optimizing genetic diversity in Australian Holsteins and Jerseys: A comparative analysis of whole-genome and regional inbreeding depression effects
No full textHomozygosity, which can arise from several genetic mechanisms including inbreeding, is frequently observed in the offspring of related parents. This inbreeding can lead to a reduced performance, owing to a phenomenon known as inbreeding depression. This study assessed inbreeding depression using whole-genome and regional approaches in first-lactation Australian Holsteins and Jerseys, involving ∼33,000 Holstein and 7,000 Jersey cows born between 2000 and 2017. These cows had phenotypic records (milk production, fertility, and survival), pedigree records, and genomic data available. We analyzed genome-wide inbreeding depression through a mixed animal model examining 4 measures of inbreeding: pedigree data, runs of homozygosity (ROH) of at least 1 Mb, ROH greater than 8 Mb, and ROH exceeding 16 Mb, which indicates more recent inbreeding. Additionally, unique ROH haplotypes, identified using a sliding-window approach, were incorporated as fixed effects in the model to estimate their effect on the traits of interest. Results indicated that a 1% increase in pedigree inbreeding led to reduced performance across all traits, with estimates of inbreeding depression ranging from 0.11% to 0.45% of the phenotypic mean. In Holsteins, genome-wide estimates (FROH) were significant and reasonably aligned with pedigree estimates, whereas more recent inbreeding (FROH >16 Mb) had between 2.6 and 3.3 times greater effect on inbreeding depression across all traits compared with smaller FROH (≥1 Mb). In Jerseys, more recent inbreeding had a 2.2 to 2.3 times greater reduction in the performance of milk and protein yields for a 1% increase in genomic inbreeding. For both fitness traits in Jerseys, the effects of inbreeding on fertility and survival were not significant. The most negative effects of ROH were also noted in specific traits: Jersey and Holstein cows with unfavorable ROH took significantly longer to recalve and showed marked reductions in production traits. Moreover, increased homozygosity in certain genomic regions, such as BTA25 in Jerseys, markedly reduced performance, highlighting the importance of genomic location in assessing the effects of homozygosity. These data inform next-generation mating programs, emphasizing avoiding inbreeding in genomic regions most susceptible to inbreeding depression, to enhance animal performance.</p
Forest transformation increases soil N<sub>2</sub>O fluxes in an unmanaged Moso bamboo forest
No full textNo description supplied.</p
An analysis of framing mechanisms used in alcohol industry submissions to an Australian national parliamentary inquiry
No full textThe aim of this study is to analyse alcohol industry submissions to an Australian national parliamentary inquiry to understand the industry arguments and their implications for alcohol policy-making, and to test, for the first time, the applicability of Campbell and colleagues' typology of framing mechanisms to alcohol industry submissions. We undertook a directed content analysis to code policy positions and arguments made by industry actors in the ten industry submissions, followed by thematic analysis to examine coded data for patterned responses according to the framing mechanisms. We identified four framing mechanisms: 'equating', 'contesting', 'dichotomizing', and 'cropping', which alcohol industry submitters used to highlight their corporate social responsibility efforts, industry leadership, self-regulation and community partnerships, while undermining effective evidence-based public health policy action. Industry submitters consistently used the inquiry as an opportunity to make arguments that supported maintenance of the regulatory 'status quo' and the continued inclusion of commercial actors as partners in policy decision-making. We identified heightened and direct attacks on public health evidence not previously seen within the Australian context. While examinations of frames remain important, stepping back and examining the framing mechanisms and actions employed can also offer insights about how to critique the discursive strategies-not just the specific arguments-being utilized by industry. From this critique, it is possible to (i) understand how some frames and arguments have gained acceptance, and others have not, and (ii) to respond to dominant frames and arguments by exposing the flaws in the discursive techniques that underpin them.</p
Extracellular vesicle profiling reveals novel autism signatures in patient-derived forebrain organoids
No full textAutism Spectrum Disorder (ASD) affects 1 percent of the world’s population with an increased prevalence of 178 percent since 2000. Although altered synaptic function putatively accounts for many of the abnormalities seen in ASD, the specific molecular mechanisms underlying this disorder remain poorly defined. A growing body of evidence suggests that extracellular vesicles (EVs), specifically exosomes, play a critical role in cellular communication within the brain. While they have been implicated in various types of diseases from cancer to neurodegeneration, their involvement in ASD remains largely unexplored. In this study, we utilized patient-derived cortical organoid models to characterize EVs secreted by human three-dimensional (3D) tissue and defined their cargo. Our study reports, for the first time, alterations in ASD organoid-derived EVs in comparison to healthy control cortical EVs. By utilizing small RNA sequencing, proteomics, nanoparticle tracking and microscopy, we provide a comprehensive characterization of the cargo carried by EVs secreted from human 3D forebrain models. Our findings reveal substantial differences both in the RNA and protein content of ASD-derived EVs, providing insight into disease mechanisms as well as highlighting the potential of exosome-based diagnostics and therapies for ASD.</p
Factors Associated With Digital Confidence and Use of Technology Among Older Queenslanders
No full textObjective: Digital technology increasingly plays an important role in supporting older adults to live longer and healthier lives. However, research consistently identifies barriers to technology usage for some older adults, particularly as they age. This study draws on data from a survey of older adults (aged 65 years and older) to improve our understanding of the role that confidence with technology plays in older adults' technology acceptance. Methods: We analysed technology usage and acceptance data from 547 Queensland older adults (53% male, 47% female) gathered as part of a larger survey examining how technology may assist the development of an in-home heat early warning system for older Queenslanders. Respondents fell within five age range groups, 65–69 years (24%), 70–74 years (29%), 75–79 years (28%), 80–84 years (12%) and 85+ (7%). Results: Respondents from the highest age range groups were more apprehensive about, and were slower to adopt, new technologies. Moreover, overall use of technology also declined with age, implying the need to consider ageing cohorts when considering technology acceptance. When looking at digital confidence, our results highlight that age was the only independent variable that predicted (inversely) digital confidence, and somewhat counterintuitively, frustration with technology. This may suggest that older cohorts avoid using new technology to avoid the risk of frustration. Conclusions: Results from the survey data add to our knowledge of the patterns of technology usage and acceptance by older adults. Our analysis underscores the need to consider variables such as confidence or frustration with technology when considering whether cutting-edge technologies will benefit older users.</p
The Most Significant Change: An Evaluation of Predictive Performance Measures in Nursing Homes
No full textRationale: Due to their frailty, older people living in nursing homes are at risk of harm if the care provided is not evidence-based and high quality. The performance measures routinely collected to measure quality care in public sector nursing homes in Victoria, Australia, are currently acute care focused and collected ‘after the fact’, so there is a need for predictive performance measures that identify circumstances that reflect poor-quality care that will cause harm to residents. Aims and Objectives: To evaluate the readiness of public sector nursing homes in Victoria, Australia to introduce predictive performance measures in aged care. Methods: A qualitative descriptive design was used to evaluate the introduction of eight predictive performance measures in six geographically diverse public sector nursing homes in Victoria, Australia. After implementing the performance measures interviews with staff were undertaken which were used to create 18 most significant change stories. The stories were workshopped by key stakeholders, to detect subtle changes in nursing home staff behaviours and clinical practice. Results: In the workshop, using the most significant change methodology six themes from the stories, each with sub-themes were identified which reflect the preparedness of nursing homes for the introduction of predictive performance measures, revealing ‘gaps’ in aged care practice, and the need for improvements. These included staff-identified strategies, changes in practice, gaps in aged care practice, areas for improvement, and the need for improvement plans, which prompted changes in staff behaviours and better care for residents. Conclusions: The study highlights the value and adaptability of using the most significant change methodology to evaluate complex interventions. This method enriches analysis by emphasising individual experiences, and the dynamics of organisational change. It highlighted subtle changes in aged care practice that would have been difficult to measure including staff behaviour, organisational culture, and the role of leadership in improving care quality for residents.</p