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Brain protein aggregates are a hallmark of neurodegenerative disease. Previous work indicates that specific protein components of these aggregates are toxic, including tau (encoded by MAPT) in Alzheimer's disease and related tauopathies. Increasing evidence also indicates that these toxic proteins traffic between cells in a prion-like fashion, thereby spreading pathology from one brain region to another. However, the mechanisms involved in trafficking are poorly understood. We therefore developed a transgenic Drosophila model to facilitate rapid evaluation of candidate tau trafficking modifiers. Our model uses the bipartite Q system to drive co-expression of tau and GFP in the fly eye. We found age-dependent spread of tau into the brain, represented by detection of tau, but not of GFP. We also found that tau trafficking was attenuated upon inhibition of the endocytic factor dynamin (encoded by shi) or knockdown of glycogen synthase kinase-3ß (GSK-3ß, encoded by sgg). Further work revealed that dynamin promoted tau uptake in recipient tissues, whereas GSK-3ß appeared to promote tau spread via direct phosphorylation of tau. Our robust and flexible system will promote the identification of tau-trafficking components involved in the pathogenesis of neurodegenerative diseases.
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Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Proteínas de Drosophila , Drosophila melanogaster , Glucógeno Sintasa Quinasa 3 beta , Proteínas tau , Animales , Proteínas tau/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Fosforilación , Encéfalo/metabolismo , Encéfalo/patología , Dinaminas/metabolismo , Transporte de Proteínas , Glucógeno Sintasa Quinasa 3/metabolismo , Humanos , Proteínas Fluorescentes Verdes/metabolismoRESUMEN
RSC Advances now offers the option of co-review for our reviewers. Editors-in-Chief Russell J. Cox and Karen Faulds, and Executive Editor Laura Fisher, offer more detail on how this will work.
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We are delighted to announce the winners of the RSC Advances Outstanding Student Paper Awards 2023. These awards recognise outstanding work published in the journal, in which a substantial component of the research was conducted by a student.
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Brain protein aggregates are a hallmark of neurodegenerative disease. Previous work indicates that specific protein components of these aggregates are toxic, including tau in Alzheimer's disease and related tauopathies. Increasing evidence also indicates that these toxic proteins traffic between cells in a prion-like fashion, thereby spreading pathology from one brain region to another. However, the mechanisms involved in trafficking are poorly understood. We therefore developed a transgenic Drosophila model to facilitate rapid evaluation of candidate tau trafficking modifiers. Our model uses the bipartite Q system to drive co-expression of tau and GFP in the fly eye. We find age-dependent tau spread into the brain, represented by detection of tau, but not GFP in the brain. We also found that tau trafficking was attenuated upon inhibition of the endocytic factor dynamin or the kinase glycogen synthase kinase-3ß ( GSK-3ß ). Further work revealed that dynamin promotes tau uptake in recipient tissues, whereas GSK-3ß appears to promote tau spread via direct phosphorylation of tau. Our robust and flexible system will promote the identification of tau trafficking components involved in the pathogenesis of neurodegenerative diseases. SUMMARY STATEMENT: The trafficking of toxic proteins in neurodegenerative disease is well-known but poorly understood. Our model will allow rapid and new insight into molecular mechanisms underlying this process.
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Sodium is an essential dietary component, but excess sodium intake can lead to high blood pressure and an increased risk of cardiovascular disease. Many national and international bodies, including the World Health Organization, have advocated for population-wide sodium reduction interventions. Most have been unsuccessful due to inadequate sodium reduction by food industry and difficulties in persuading consumers to add less salt to food. Recent research highlights potassium-enriched salt as a new, feasible, acceptable, and scalable approach to reducing the harms caused by excess sodium and inadequate potassium consumption. Modeling shows that a global switch from regular salt to potassium-enriched salt has the potential to avert millions of strokes, heart attacks, and premature deaths worldwide each year. There will be many challenges in switching the world's salt supply to potassium-enriched salt, but the success of universal salt iodization shows that making a global change to the manufacture and use of salt is a tractable proposition. This in-depth review of universal salt iodization identified the importance of a multisectoral effort with strong global leadership, the support of multilateral organizations, engagement with the salt industry, empowered incountry teams, strong participation of national governments, understanding the salt supply chain, and a strategic advocacy and communication plan. Key challenges to the implementation of the iodization program were costs to government, industry, and consumers, industry concerns about consumer acceptability, variance in the size and capabilities of salt producers, inconsistent quality control, ineffective regulation, and trade-related regulatory issues. Many of the opportunities and challenges to universal salt iodization will likely also be applicable to switching the global salt supply to iodized and potassium-enriched salt.
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Yodo , Potasio , Humanos , Cloruro de Sodio Dietético , Alimentos , SodioRESUMEN
We are delighted to announce the winners for the RSC Advances Outstanding Student Paper Awards 2022. These awards recognise outstanding work published in the journal, for which a substantial component of the research was conducted by a student.
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RSC Advances is introducing the option of transparent peer review for authors. Editors-in-Chief Russell J. Cox and Karen Faulds, and Executive Editor Laura C. Fisher offer more detail on how this will work.
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Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based treatments for cLBP. Thus, we will conduct a randomized controlled Sequential, Multiple Assessment, Randomized Trial (SMART) design study in cLBP with the following three aims. Aim 1: Perform an interventional response phenotyping study in a cohort of cLBP patients (n = 400), who will receive a sequence of interventions known to be effective in cLBP. For 4 weeks, all cLBP participants will receive a web-based pain self-management program as part of a run-in period, then individuals who report no or minimal improvement will be randomized to: a) mindfulness-based stress reduction, b) physical therapy and exercise, c) acupressure self-management, and d) duloxetine. After 8 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 8 weeks. Using those data, we will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically derived measures, can predict differential responsiveness to the treatments. In Aim 3, a subset of participants will receive deeper phenotyping (n = 160), to identify new experimental measures that predict differential responsiveness to the treatments, as well as to infer mechanisms of action. Deep phenotyping will include functional neuroimaging, quantitative sensory testing, measures of inflammation, and measures of autonomic tone.
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Dolor Crónico , Dolor de la Región Lumbar , Humanos , Dolor Crónico/terapia , Dolor de la Región Lumbar/terapia , Modalidades de Fisioterapia , Proyectos de Investigación , Clorhidrato de Duloxetina , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Expression of concern for 'Ultrafine carbamazepine nanoparticles with enhanced water solubility and rate of dissolution' by Raj Kumar et al., RSC Adv., 2014, 4, 48101-48108, https://doi.org/10.1039/C4RA08495K.
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[This retracts the article DOI: 10.1039/D0RA06093C.].
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[This retracts the article DOI: 10.1039/C9RA00089E.].
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[This retracts the article DOI: 10.1039/C9RA06408G.].
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[This retracts the article DOI: 10.1039/C9RA06284J.].
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[This retracts the article DOI: 10.1039/C9RA01623F.].
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[This retracts the article DOI: 10.1039/C9RA00090A.].
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[This retracts the article DOI: 10.1039/C9RA03965A.].
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[This retracts the article DOI: 10.1039/C8RA09018A.].
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[This retracts the article DOI: 10.1039/C9RA01609K.].
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Expression of concern for 'Bone marrow mesenchymal stem cells inhibited bleomycin-induced lung fibrosis' by Jiang Nan et al., RSC Adv., 2017, 7, 49498-49504. DOI: 10.1039/C7RA03971A.