681 research outputs found

    Global analysis reveals the complexity of the human glomerular extracellular matrix.

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    The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456

    Insights into the complexity of presentation and management of patients: The sport and exercise physician’s perspective

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    Objectives: Sport and Exercise Physicians represent a relatively new specialty focusing on exercise in complex diseases including musculoskeletal diseases. Our objective was to describe the characteristics, type and complexity of patient presentations, their management strategies and referral information in Australian practice. Methods: A cross-sectional study including a cohort of 11 senior Sport and Exercise Physicians in Australia studied all new patient consultations within an 8-week period. Data were analysed relating to presentation, referral source, follow-up referrals, and patient management strategies. Results: Data from 419 patients were recorded. The majority, 97% (n=406), had musculoskeletal conditions, 53% (n=222) had one or more associated comorbidities and 47% (n=195) had ongoing symptoms for \u3e 12 months. Most patients, 82% (n=355), were referred by general practitioners. Prior consultations included physiotherapy 72% (n=301) and orthopaedic 20% (n=85). A multidisciplinary network of referrals from Sport and Exercise Physicians was observed, including 210 referrals to 9 allied health specialities and 61 referrals to 17 medical specialities. Over 74% (n=311) of patients received exercise-based intervention as part of the treatment plan, including 57% (n=240) physician managed exercise interventions. Conclusion: Our work shines a light on the nature and complexity of the role of Sport and Exercise Physicians in an Australian practice context. Findings will assist in implementing measures to promote patient care at the community level in managing musculoskeletal conditions. Sport and exercise medicine stakeholders and government policy makers can use this information in developing appropriate programmes to support patients and create integrated sport and exercise medicine services for the community

    Kinship, dear enemies, and costly combat:The effects of relatedness on territorial overlap and aggression in a cooperative breeder

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    Many species maintain territories, but the degree of overlap between territories and the level of aggression displayed in territorial conflicts can vary widely, even within species. Greater territorial overlap may occur when neighboring territory holders are close relatives. Animals may also differentiate neighbors from strangers, with more familiar neighbors eliciting less‐aggressive responses during territorial conflicts (the “dear enemy” effect). However, research is lacking in how both kinship and overlap affect territorial conflicts, especially in group‐living species. Here, we investigate kinship, territorial overlap, and territorial conflict in a habituated wild population of group‐living cooperatively breeding birds, the southern pied babbler Turdoides bicolor. We find that close kin neighbors are beneficial. Territories overlap more when neighboring groups are close kin, and these larger overlaps with kin confer larger territories (an effect not seen for overlaps with unrelated groups). Overall, territorial conflict is costly, causing significant decreases in body mass, but conflicts with kin are shorter than those conducted with nonkin. Conflicts with more familiar unrelated neighbors are also shorter, indicating these neighbors are “dear enemies.” However, kinship modulates the “dear enemy” effect; even when kin are encountered less frequently, kin elicit less‐aggressive responses, similar to the “dear enemy” effect. Kin selection appears to be a main influence on territorial behavior in this species. Groups derive kin‐selected benefits from decreased conflicts and maintain larger territories when overlapping with kin, though not when overlapping with nonkin. More generally, it is possible that kinship extends the “dear enemy” effect in animal societies

    Dysregulation of alternative poly-adenylation as a potential player in Autism Spectrum Disorder

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    We present here the hypothesis that alternative poly-adenylation (APA) is dysregulated in the brains of individuals affected by Autism Spectrum Disorder (ASD), due to disruptions in the calcium signaling networks. APA, the process of selecting different poly-adenylation sites on the same gene, yielding transcripts with different-length 3â€Č untranslated regions (UTRs), has been documented in different tissues, stages of development and pathologic conditions. Differential use of poly-adenylation sites has been shown to regulate the function, stability, localization and translation efficiency of target RNAs. However, the role of APA remains rather unexplored in neurodevelopmental conditions. In the human brain, where transcripts have the longest 3â€Č UTRs and are thus likely to be under more complex post-transcriptional regulation, erratic APA could be particularly detrimental. In the context of ASD, a condition that affects individuals in markedly different ways and whose symptoms exhibit a spectrum of severity, APA dysregulation could be amplified or dampened depending on the individual and the extent of the effect on specific genes would likely vary with genetic and environmental factors. If this hypothesis is correct, dysregulated APA events might be responsible for certain aspects of the phenotypes associated with ASD. Evidence supporting our hypothesis is derived from standard RNA-seq transcriptomic data but we suggest that future experiments should focus on techniques that probe the actual poly-adenylation site (3â€Č sequencing). To address issues arising from the use of post-mortem tissue and low numbers of heterogeneous samples affected by confounding factors (such as the age, gender and health of the individuals), carefully controlled in vitro systems will be required to model the effect of calcium signaling dysregulation in the ASD brain
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