8 research outputs found
Cross-seeding by prion protein inactivates TDP-43
No full textAbstract A common pathological denominator of various neurodegenerative diseases is the accumulation of protein aggregates. Neurotoxic effects are caused by a loss of the physiological activity of the aggregating protein and/or a gain of toxic function of the misfolded protein conformers. In transmissible spongiform encephalopathies or prion diseases, neurodegeneration is caused by aberrantly folded isoforms of the prion protein (PrP). However, it is poorly understood how pathogenic PrP conformers interfere with neuronal viability. Employing in vitro approaches, cell culture, animal models, and patients’ brain samples, we show that misfolded PrP can induce aggregation and inactivation of TDP-43. Purified PrP aggregates interact with TDP-43 in vitro and in cells and induce the conversion of soluble TDP-43 into non-dynamic protein assemblies. Similarly, mislocalized PrP conformers in the cytosol bind to and sequester TDP-43 in cytosolic aggregates. As a consequence, TDP-43-dependent splicing activity in the nucleus is significantly decreased, leading to altered protein expression in cells with cytosolic PrP aggregates. Finally, we present evidence for cytosolic TDP-43 aggregates in neurons of transgenic flies expressing mammalian PrP and Creutzfeldt–Jakob disease patients. Our study identified a novel mechanism of how aberrant PrP conformers impair physiological pathways by cross-seeding
Bulk and surface modification of elastomers by electron beam irradation: Structure-property relationship
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Behavioural activation therapy for depression in adults with non-communicable diseases
No full textBACKGROUND: Depression is common in people with non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. The co-existence of depression and NCDs may affect health behaviours, compliance with treatment, physiological factors, and quality of life. This in turn is associated with worse outcomes for both conditions. Behavioural activation is not currently indicated for the treatment of depression in this population in the UK, but is increasingly being used to treat depression in adults. OBJECTIVES: To examine the effects of behavioural activation compared with any control group for the treatment of depression in adults with NCDs. To examine the effects of behavioural activation compared with each control group separately (no treatment, waiting list, other psychological therapy, pharmacological treatment, or any other type of treatment as usual) for the treatment of depression in adults with NCDs. SEARCH METHODS: We searched CCMD-CTR, CENTRAL, Ovid MEDLINE, Embase, four other databases, and two trial registers on 4 October 2019 to identify randomised controlled trials (RCTs) of behavioural activation for depression in participants with NCDs, together with grey literature and reference checking. We applied no restrictions on date, language, or publication status to the searches. SELECTION CRITERIA: We included RCTs of behavioural activation for the treatment of depression in adults with one of four NCDs: cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. Only participants with a formal diagnosis of both depression and an NCD were eligible. Studies were included if behavioural activation was the main component of the intervention. We included studies with any comparator that was not behavioural activation, and regardless of reported outcomes. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane, including independent screening of titles/abstracts and full-text manuscripts, data extraction, and risk of bias assessments in duplicate. Where necessary, we contacted study authors for more information. MAIN RESULTS: We included two studies, contributing data from 181 participants to the analyses. Both studies recruited participants from US hospital clinics; one included people who were recovering from a stroke and the other women with breast cancer. For both studies, the intervention consisted of eight weeks of face-to-face behavioural therapy, with one study comparing to poststroke treatment as usual and the other comparing to problem-solving therapy. Both studies were at risk of performance bias and potential conflict of interest arising from author involvement in the development of the intervention. For one study, risks of selection bias and reporting bias were unclear and the study was judged at high risk of attrition bias. Treatment efficacy (remission) was greater for behavioural activation than for comparators in the short term (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.98 to 2.38; low-certainty evidence) and medium term (RR 1.76, 95% CI 1.01 to 3.08; moderate-certainty evidence), but these estimates lacked precision and effects were reduced in the long term (RR 1.42, 95% CI 0.91 to 2.23; moderate-certainty evidence). We found no evidence of a difference in treatment acceptability in the short term (RR 1.81, 95% CI 0.68 to 4.82) and medium term (RR 0.88, 95% CI 0.25 to 3.10) (low-certainty evidence). There was no evidence of a difference in depression symptoms between behavioural activation and comparators (short term: MD -1.15, 95% CI -2.71 to 0.41; low-certainty evidence). One study found no difference for quality of life (short term: MD 0.40, 95% CI -0.16 to 0.96; low-certainty evidence), functioning (short term: MD 2.70, 95% CI -6.99 to 12.39; low-certainty evidence), and anxiety symptoms (short term: MD -1.70, 95% CI -4.50 to 1.10; low-certainty evidence). Neither study reported data on adverse effects. AUTHORS' CONCLUSIONS: Evidence from this review was not sufficient to draw conclusions on the efficacy and acceptability of behavioural activation for the treatment of depression in adults with NCDs. A future review may wish to include, or focus on, studies of people with subthreshold depression or depression symptoms without a formal diagnosis, as this may inform whether behavioural activation could be used to treat mild or undiagnosed (or both) depressive symptoms in people with NCDs. Evidence from low-resource settings including low- and middle-income countries, for which behavioural activation may offer a feasible alternative to other treatments for depression, would be of interest
Land Suitability Investigation for Solar Power Plant Using GIS, AHP and Multi-Criteria Decision Approach: A Case of Megacity Kolkata, West Bengal, India
No full textRenewable energy sources are the most necessitated natural energy to reduce fossil fuels globally. Fossil fuel is the most valuable and limited resource on the planet, but on the other hand, renewable energy creates less pollution. Solar energy is the most effective renewable resource for daily use. Solar power plants are necessary for domestic and daily use. Remote sensing and geographic information technology (GIS) were used for this study to delineate the possible site selection of solar power plants in Kolkata and the surrounding area in West Bengal, India. The analytical hierarchy process (AHP) and the multi-criteria decision-making process (MCDA) were used for each weight calculation and ArcGIS v10.8 was applied for weighted overlay analysis (WOA) for delineation of the result. The site suitability map was developed using a pairwise comparison matrix and the weights were calculated for each criterion. The suitability map was divided into five categories, from not suitable to very highly suitable. A total of 474.21 km2 (10.69%) of the area was classified as very highly suitable whereas 249.54 km2 (5.62%) area was classified as not suitable because of the water area and east Kolkata wetland. A total of 1438.15 km2 (32.43%) of the area was classified as highly suitable for a solar power plant. The Kolkata megacity and water body locations were identified as moderate to not suitable sites. Very high and high-potential sites were identified 2 to 5 km from the central business district (CBD) location, which is Dharmotala. Renewable energy source is needed in the megacity of Kolkata. If solar power plants are contracted then the demand for fossil fuel will be reduced one day, and that will help the environment as well as the society in terms of sustainable development. This study result is helpful for administrators, urban planners, developers, and other stakeholders for the implementation and development of a new solar power plant in the study area
Large-Scale Flood Hazard Monitoring and Impact Assessment on Landscape: Representative Case Study in India
No full textCurrently, natural hazards are a significant concern as they contribute to increased vulnerability, environmental degradation, and loss of life, among other consequences. Climate change and human activities are key factors that contribute to various natural hazards such as floods, landslides, droughts, and deforestation. Assam state in India experiences annual floods that significantly impact the local environment. In 2022, the flooding affected approximately 1.9 million people and 2930 villages, resulting in the loss of 54 lives. This study utilized the Google Earth Engine (GEE) cloud-computing platform to investigate the extent of flood inundation and deforestation, analyzing pre-flood and post-flood C band Sentinel-1 GRD datasets. Identifying pre- and post-flood areas was conducted using Landsat 8–9 OLI/TIRS datasets and the modified and normalized difference water index (MNDWI). The districts of Cachar, Kokrajhar, Jorhat, Kamrup, and Dhubri were the most affected by floods and deforestation. The 2022 Assam flood encompassed approximately 24,507.27 km2 of vegetation loss and 33,902.49 km2 of flood inundation out of a total area of 78,438 km2. The most affected areas were the riverine regions, the capital city Dispur, Guwahati, southern parts of Assam, and certain eastern regions. Flood hazards exacerbate environmental degradation and deforestation, making satellite-based information crucial for hazard and disaster management solutions. The findings of this research can contribute to raising awareness, planning, and implementing future disaster management strategies to protect both the environment and human life
VCP/p97 mediates nuclear targeting of non-ER-imported prion protein to maintain proteostasis
No full textMistargeting of secretory proteins in the cytosol can trigger their aggregation and subsequent proteostasis decline. We have identified a VCP/p97-dependent pathway that directs non-ER-imported prion protein (PrP) into the nucleus to prevent the formation of toxic aggregates in the cytosol. Upon impaired translocation into the ER, PrP interacts with VCP/p97, which facilitates nuclear import mediated by importin-. Notably, the cytosolic interaction of PrP with VCP/p97 and its nuclear import are independent of ubiquitination. In vitro experiments revealed that VCP/p97 binds non-ubiquitinated PrP and prevents its aggregation. Inhibiting binding of PrP to VCP/p97, or transient proteotoxic stress, promotes the formation of self-perpetuating and partially proteinase resistant PrP aggregates in the cytosol, which compromised cellular proteostasis and disrupted further nuclear targeting of PrP. In the nucleus, RNAs keep PrP in a soluble and non-toxic conformation. Our study revealed a novel ubiquitin-independent role of VCP/p97 in the nuclear targeting of non-imported secretory proteins and highlights the impact of the chemical milieu in triggering protein misfolding
