doi: bioRxiv preprint their components rapidly with the surrounding medium (Hyman et al., 2014;. Most of the liquid condensates possess common characteristics, which include their formation mechanism as well as their physical properties. For instance, multivalent proteins or nucleic acids associate through weak intermolecular interactions and reach a solubility limit to form liquid condensates (Banani et al., 2017;. These condensates are highly mobile, spherical, but get deformed on physical contact, fuse and eventually relax back to their spherical shape (Brangwynne et al., 2009;Brangwynne et al., 2011;Molliex et al., 2015;Nott et al., 2015). Several proteins undergoing LLPS, however, contain intrinsically disordered regions (IDRs) that are closely associated with prion-like domains (PLDs) and low complexity domains (LCDs) (
The transcriptional regulator p53 has an essential role in tumor suppression. Almost 50% of human cancers are associated with the loss of p53 functions, where p53 often accumulates in the nucleus as well as in cytoplasm. Although it has been previously suggested that amyloid formation could be a cause of p53 loss-of-function in subset of tumors, the characterization of these amyloids and its structure-function relationship is not yet established. In the current study, we provide several evidences for the presence of p53 amyloid formation (in human and animal cancer tissues); along with its isolation from human cancer tissues and the biophysical characterization of these tissue-derived fibrils. Using amyloid seed of p53 fragment (P8, p53(250-257)), we show that p53 amyloid formation in cells not only leads to its functional inactivation but also transforms it into an oncoprotein. The in vitro studies further show that cancer-associated mutation destabilizes the fold of p53 core domain and also accelerates the aggregation and amyloid formation by this protein. Furthermore, we also show evidence of prion-like cell-to-cell transmission of different p53 amyloid species including full-length p53, which is induced by internalized P8 fibrils. The present study suggests that p53 amyloid formation could be one of the possible cause of p53 loss of function and therefore, inhibiting p53 amyloidogenesis could restore p53 tumor suppressor functions.
India faces major environmental challenges associated with waste generation and inadequate waste collection, transport, treatment and disposal. Current systems in India cannot cope with the volumes of waste generated by an increasing urban population, and this impacts on the environment and public health. The challenges and barriers are significant, but so are the opportunities. This paper reports on an international seminar on ‘Sustainable solid waste management for cities: opportunities in South Asian Association for Regional Cooperation (SAARC) countries’ organized by the Council of Scientific and Industrial Research-National Environmental Engineering Research Institute and the Royal Society. A priority is to move from reliance on waste dumps that offer no environmental protection, to waste management systems that retain useful resources within the economy. Waste segregation at source and use of specialized waste processing facilities to separate recyclable materials has a key role. Disposal of residual waste after extraction of material resources needs engineered landfill sites and/or investment in waste-to-energy facilities. The potential for energy generation from landfill via methane extraction or thermal treatment is a major opportunity, but a key barrier is the shortage of qualified engineers and environmental professionals with the experience to deliver improved waste management systems in India.
Air pollution (AP) is one of the major causes of health risks as it leads to widespread morbidity and mortality each year. Its environmental impacts include acid rains, reduced visibility, but more importantly and significantly, it affects human health. The price tag of not managing AP is seen in the rise of chronic obstructive pulmonary disease (COPD), cardiovascular disease, and respiratory ailments like asthma and chronic bronchitis. But as the world battles the corona pandemic, COVID-19 lockdown has abruptly halted human activity, leading to a significant reduction in AP levels. The effect of this reduction is captured by reduced cases of morbidity and mortality associated with air pollution. The current study aims to monetarily quantify the decline in health impacts due to reduced AP levels under lockdown scenario, as against business as usual, for four cities-Delhi, London, Paris, and Wuhan. The exposure assessment with respect to pollutants like particulate matter (PM 2.5 and PM 10 ), NO 2 , and SO 2 are evaluated. Value of statistical life (VSL), cost of illness (CoI), and per capita income (PCI) for disability-adjusted life years (DALY) are used to monetize the health impacts for the year 2019 and 2020, considering the respective period of COVID-19 lockdown of four cities. The preventive benefits related to reduced AP due to lockdown is evaluated in comparison to economic damage sustained by these four cities. This helps in understanding the magnitude of actual damage and brings out a more holistic picture of the damages related to lockdown.
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