19683 research outputs found
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Dystrophin S3059 phosphorylation partially attenuates denervation atrophy in mouse tibialis anterior muscles
No full textThe dystrophin protein has well-characterized roles in force transmission and maintaining membrane integrity during muscle contraction. Studies have reported decreased expression of dystrophin in atrophying muscles during wasting conditions, and that restoration of dystrophin can attenuate atrophy, suggesting a role in maintaining muscle mass. Phosphorylation of S3059 within the cysteine-rich region of dystrophin enhances binding between dystrophin and β-dystroglycan, and mimicking phosphorylation at this site by site-directed mutagenesis attenuates myotube atrophy in vitro. To determine whether dystrophin phosphorylation can attenuate muscle wasting in vivo, CRISPR-Cas9 was used to generate mice with whole body mutations of S3059 to either alanine (DmdS3059A) or glutamate (DmdS3059E), to mimic a loss of, or constitutive phosphorylation of S3059, on all endogenous dystrophin isoforms, respectively. Sciatic nerve transection was performed on these mice to determine whether phosphorylation of dystrophin S3059 could attenuate denervation atrophy. At 14 days post denervation, atrophy of tibialis anterior (TA) but not gastrocnemius or soleus muscles, was partially attenuated in DmdS3059E mice relative to WT mice. Attenuation of atrophy was associated with increased expression of β-dystroglycan in TA muscles of DmdS3059E mice. Dystrophin S3059 phosphorylation can partially attenuate denervation-induced atrophy, but may have more significant impact in less severe modes of muscle wasting
The use of digital technologies in the sport and physical education lesson: Fostering need-supportive behaviours in physical education teachers
No full textIn primary and high school settings, the benefits of incorporating technology into curricula have been addressed by several studies; however, wearable technology integration as experienced by physical education teachers is less prevalent. Physical education teachers’ lack of confidence teaching P.E. using wearables, along with a lack of appropriate preparation and unclear curricula frameworks that define how wearables could be used, are additional factors which require further exploration. As such, due consideration of the opportunities and barriers that physical education teachers encounter with wearable usage is presented. This article contributes to pedagogical practices in physical education using wearable technology. This is achieved by highlighting the opportunities that wearable technology presents as a student learning support tool as wearable allow cross curriculum learning opportunities with science, technology, engineering and mathematics. In this paper, the practicality and curriculum relevance of wearable usage in physical education is highlighted. Our paper discusses implications for research and practice and provides a knowledge base for the establishment of professional development courses based on teacher needs.</p
HB-EGF-loaded nanovesicles enhance trophectodermal spheroid attachment and invasion.
No full textThe ability of trophectodermal cells (outer layer of the embryo) to attach to the endometrial cells and subsequently invade the underlying matrix are critical stages of embryo implantation during successful pregnancy establishment. Extracellular vesicles (EVs) have been implicated in embryo-maternal crosstalk, capable of reprogramming endometrial cells towards a pro-implantation signature and phenotype. However, challenges associated with EV yield and direct loading of biomolecules limit their therapeutic potential. We have previously established generation of cell-derived nanovesicles (NVs) from human trophectodermal cells (hTSCs) and their capacity to reprogram endometrial cells to enhance adhesion and blastocyst outgrowth. Here, we employed a rapid NV loading strategy to encapsulate potent implantation molecules such as HB-EGF (NVHBEGF). We show these loaded NVs elicit EGFR-mediated effects in recipient endometrial cells, activating kinase phosphorylation sites that modulate their activity (AKT S124/129, MAPK1 T185/Y187), and downstream signalling pathways and processes (AKT signal transduction, GTPase activity). Importantly, they enhanced target cell attachment and invasion. The phosphoproteomics and proteomics approach highlight NVHBEGF-mediated short-term signalling patterns and long-term reprogramming capabilities on endometrial cells which functionally enhance trophectodermal-endometrial interactions. This proof-of-concept study demonstrates feasibility in enhancing the functional potency of NVs in the context of embryo implantation
The Rinehart sanction: How crude philanthropy and clumsy gratitude can undermine our democratic ideals
No full textNo description supplied.</p
Whose voice is it anyway? Adults with intellectual disabilities and future planning: A scoping review of qualitative studies
No full textBackground: Future planning is a way of supporting people with intellectual disabilities and their families to think about their support needs as both groups age. Adults with intellectual disabilities, family members, and service providers are often involved in planning processes. However, it is unclear whose perspectives dominate in the literature and how these might vary. Method: A scoping review of qualitative studies (2012–2022) was undertaken to identify which perspectives are present in research on adults with intellectual disabilities and future planning, and to examine key aspects of their future planning experience. Results: The perspectives of parents and siblings predominate in the research. Those of adults with intellectual disabilities and service providers are underrepresented. Conclusions: The views of adults with intellectual disabilities need to be elevated in future planning and they need to be meaningfully involved in planning processes. Focus on the experiences of service providers is likewise needed
Prevalence of toddlers meeting 24-hour movement guidelines and associations with parental perceptions and practices
No full textObjectives: Whether toddlers (1-2 years) meet 24-hour Movement Guidelines and how parental practices and perceptions are related to compliance are uncertain. This study: a) estimated the proportion of toddlers meeting individual and combined movement guidelines; and b) examined associations between parental perceptions/practices and toddlers’ compliance with movement guidelines. Design: Cross-sectional study. Methods: Australian parents self-reported their parenting practices/perceptions (routines, co-participation, restrictions, concerns, knowledge) and toddlers’ movement behaviours in the baseline assessment of Let's Grow (n=1145), a randomised controlled trial. The World Health Organization's Guidelines on Physical Activity, Sedentary Behaviour, and Sleep for children under 5 years were used to estimate the prevalence of compliance with individual and combined movement guidelines. Logistic models assessed cross-sectional associations. Results: The prevalence of meeting guidelines was 30.9% for screen time, 82.3% for sleep, 81.6% for physical activity, 20.1% for combined, and 2.1% meeting none. Parents’ knowledge of the guidelines, fewer concerns and more favourable restrictions concerning movement behaviours were associated with greater compliance with individual and combined movement guidelines. Routines for screen time and for combined behaviours were associated with adherence to their respective guidelines. Less co-participation in screen time and more co-participation in physical activity were associated with greater compliance with the relevant guidelines. Conclusions: Given only 20% of toddlers met all guidelines, strategies early in life to establish healthy movement behaviours, especially screen time, are needed. Future studies could target the parental practices/perceptions identified in this study to support toddlers with optimal sleep and physical activity and reduced screen time.</p
Achieving Carbon-Neutrality in MENA Countries: Does Financial Inclusion Matter?
No full textThis study examines the relationship between financial inclusion, renewable energy, and CO2 emissions using data from 11 Middle East and North Africa (MENA) countries from 2004 to 2019. Evidence from fixed effects-ordinary least squares (FE-OLS), dynamic ordinary least squares (DOLS), fully modified ordinary least squares (FMOLS), and canonical correlation regression (CRR) showed that financial inclusion contributes significantly to decarbonization. Country-specific analysis indicated that financial inclusion is associated with mitigating CO2 emissions in Egypt, Israel, Qatar, and Tunisia while significantly spurring CO2 emissions in Algeria, Lebanon, and Saudi Arabia. In addition, renewable energy contributes significantly to decarbonization in MENA, especially in Algeria, Lebanon, Tunisia, and Turkey. We recommend that policies promoting financial inclusion and renewable energy usage would contribute to the attainment of the carbon-neutrality goal by MENA countries
Data and associated outputs for alpine streams script
No full textThese files are associated with the script "alpine warming impacts aquatic ectotherms" (https://doi.org/10.26181/24303055.v1) and the manuscript "Out of the frying pan into the fire: predicted warming in alpine streams suggests hidden consequences for aquatic ectotherms", by Shackleton et al (2024) published in Global Change Biology. They contain raw data used in the script as well as model objects and model outputs created with the script.</p
DeepKEGG: a multi-omics data integration framework with biological insights for cancer recurrence prediction and biomarker discovery
No full textAbstract: Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG.</p
Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers
No full textSummary: TP53-mutant blood cancers remain a clinical challenge. BH3-mimetic drugs inhibit BCL-2 pro-survival proteins, inducing cancer cell apoptosis. Despite acting downstream of p53, functional p53 is required for maximal cancer cell killing by BH3-mimetics through an unknown mechanism. Here, we report p53 is activated following BH3-mimetic induced mitochondrial outer membrane permeabilization, leading to BH3-only protein induction and thereby potentiating the pro-apoptotic signal. TP53-deficient lymphomas lack this feedforward loop, providing opportunities for survival and disease relapse after BH3-mimetic treatment. The therapeutic barrier imposed by defects in TP53 can be overcome by direct activation of the cGAS/STING pathway, which promotes apoptosis of blood cancer cells through p53-independent BH3-only protein upregulation. Combining clinically relevant STING agonists with BH3-mimetic drugs efficiently kills TRP53/TP53-mutant mouse B lymphoma, human NK/T lymphoma, and acute myeloid leukemia cells. This represents a promising therapy regime that can be fast-tracked to tackle TP53-mutant blood cancers in the clinic.</p