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•Polystyrene microplastics (PS-MPs) cause pulmonary cytotoxicity by inducing ROS.•PS-MPs is associated with impaired pulmonary barrier by depleting ZO proteins.•PS-MPs inhalation ...increases the risk for chronic obstructive pulmonary disease.
Microplastics (MPs) have become a global environmental concern. Recent studies have shown that MPs, of which the predominant type is often polystyrene (PS; known as PS-MPs), can extend to and affect remote, sparsely inhabited areas via atmospheric transport. Although exposure to inhaled MPs may induce lung dysfunction, further experimental verification of the pulmonary toxic potential of MPs and the mechanism underlying the toxicity is needed. Here we used normal human lung epithelial BEAS-2B cells to clarify the association between pulmonary toxicity and PS-MPs. Results revealed that PS-MPs can cause cytotoxic and inflammatory effects in BEAS-2B cells by inducing reactive oxygen species formation. PS-MPs can decrease transepithelial electrical resistance by depleting zonula occludens proteins. Indeed, decreased α1-antitrypsin levels in BEAS-2B cells suggest that exposure to PS-MPs increases the risk for chronic obstructive pulmonary disease, and high concentrations of PS-MPs can induce these adverse responses. While low PS-MP levels can only disrupt the protective pulmonary barrier, they may also increase the risk for lung disease. Collectively, our findings indicate that PS-MP inhalation may influence human respiratory health.
Due to its low cost, environmentally friendly process, and lack of secondary contamination, the photodegradation of dyes is regarded as a promising technology for industrial wastewater treatment. ...This technology demonstrates the light-enhanced generation of charge carriers and reactive radicals that non-selectively degrade various organic dyes into water, CO2, and other organic compounds via direct photodegradation or a sensitization-mediated degradation process. The overall efficiency of the photocatalysis system is closely dependent upon operational parameters that govern the adsorption and photodegradation of dye molecules, including the initial dye concentration, pH of the solution, temperature of the reaction medium, and light intensity. Additionally, the charge-carrier properties of the photocatalyst strongly affect the generation of reactive species in the heterogeneous photodegradation and thereby dictate the photodegradation efficiency. Herein, this comprehensive review discusses the pseudo kinetics and mechanisms of the photodegradation reactions. The operational factors affecting the photodegradation of either cationic or anionic dye molecules, as well as the charge-carrier properties of the photocatalyst, are also fully explored. By further analyzing past works to clarify key active species for photodegradation reactions and optimal conditions, this review provides helpful guidelines that can be applied to foster the development of efficient photodegradation systems.
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that ...epithelial-mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs. We further identify a non-canonical mesenchymal-epithelial transition (MET) activity of etoposide, which suppresses the EMT/β-catenin/STT3/PD-L1 axis through TOP2B degradation-dependent nuclear β-catenin reduction, leading to PD-L1 downregulation of CSCs and non-CSCs and sensitization of cancer cells to anti-Tim-3 therapy. Together, our results link MET to PD-L1 stabilization through glycosylation regulation and reveal it as a potential strategy to enhance cancer immunotherapy efficacy.
We consider a general social choice environment that has multiple agents, a finite set of alternatives, independent types, and atomless type distribution. We show that for any Bayesian incentive ...compatible mechanism, there exists an equivalent deterministic mechanism that (1) is Bayesian incentive compatible; (2) delivers the same interim expected allocation probabilities and the same interim expected utilities for all agents; and (3) delivers the same ex ante expected social surplus. This result holds in settings with a rich class of utility functions, multidimensional types, interdependent valuations, and in settings without monetary transfers. To prove our result, we develop a novel methodology of mutual purification, and establish its link with the mechanism design literature.
The Clinical Dementia Rating (CDR) Scale comprising global score (CDR-GS) and sum of boxes scores (CDR-SB) is commonly used in staging cognitive impairment; however, its diagnostic accuracy is not ...well clarified. The meta-analysis aimed to investigate the diagnostic accuracy of the CDR for mild cognitive impairment (MCI) and dementia in older populations.
Studies examining the diagnostic accuracy of the CDR for MCI or dementia against reference standards were included from seven electronic databases. The bivariate analysis with a random-effects model was adopted to calculate the pooled sensitivity and specificity of the CDR for MCI and dementia.
Fifteen studies investigating the diagnostic accuracy of the CDR-GS (n = 13) or CDR-SB (n = 5) for MCI or dementia were included. The pooled sensitivity and specificity of the CDR-GS for MCI were 93% and 97%, respectively. With respect to dementia, the CDR-GS had superior pooled specificity compared to the CDR-SB (99% vs. 94%), while similar sensitivities were found between the CDR-GS and CDR-SB (both 87%). Significant moderators of an old age, a high educational level, a high prevalence of MCI or dementia, being in a developing country, and a lack of informants' observations may affect the estimation of the sensitivity or specificity of the CDR.
Evidence supports the CDR being useful for detecting MCI and dementia; applying the CDR for staging cognitive impairment in at risk populations should be considered. Furthermore, including objective observations from relevant informants or proxies to increase the accuracy of the CDR for dementia is suggested.
We examine how mandatory disclosure of corporate social responsibility (CSR) impacts firm performance and social externalities. Our analysis exploits China's 2008 mandate requiring firms to disclose ...CSR activities, using a difference-in-differences design. Although the mandate does not require firms to spend on CSR, we find that mandatory CSR reporting firms experience a decrease in profitability subsequent to the mandate. In addition, the cities most impacted by the disclosure mandate experience a decrease in their industrial wastewater and SO2 emission levels. These findings suggest that mandatory CSR disclosure alters firm behavior and generates positive externalities at the expense of shareholders.
Islet prohormone processing in health and disease Chen, Yi‐Chun; Taylor, Austin J.; Verchere, C. Bruce
Diabetes, obesity & metabolism,
September 2018, 2018-09-00, 20180901, Letnik:
20, Številka:
S2
Journal Article
Odprti dostop
Biosynthesis of peptide hormones by pancreatic islet endocrine cells is a tightly orchestrated process that is critical for metabolic homeostasis. Like neuroendocrine peptides, insulin and other ...islet hormones are first synthesized as larger precursor molecules that are processed to their mature secreted products through a series of proteolytic cleavages, mediated by the prohormone convertases Pc1/3 and Pc2, and carboxypeptidase E. Additional posttranslational modifications including C‐terminal amidation of the β‐cell peptide islet amyloid polypeptide (IAPP) by peptidyl‐glycine α‐amidating monooxygenase (Pam) may also occur. Genome‐wide association studies (GWAS) have showed genetic linkage of these processing enzymes to obesity, β‐cell dysfunction, and type 2 diabetes (T2D), pointing to their important roles in metabolism and blood glucose regulation. In both type 1 diabetes (T1D) and T2D, and in the face of metabolic or inflammatory stresses, islet prohormone processing may become impaired; indeed elevated proinsulin:insulin (PI:I) ratios are a hallmark of the β‐cell dysfunction in T2D. Recent studies suggest that genetic or acquired defects in proIAPP processing may lead to the production and secretion of incompletely processed forms of proIAPP that could contribute to T2D pathogenesis, and additionally that impaired processing of both PI and proIAPP may be characteristic of β‐cell dysfunction in T1D. In islet α‐cells, the prohormone proglucagon is normally processed to bioactive glucagon by Pc2 but may express Pc1/3 under certain conditions leading to production of GLP‐1(7‐36NH2). A better understanding of how β‐cell processing of PI and proIAPP, as well as α‐cell processing of proglucagon, are impacted by genetic susceptibility and in the face of diabetogenic stresses, may lead to new therapeutic approaches for improving islet function in diabetes.
Double-strand breaks activate the ataxia telangiectasia mutated (ATM) kinase, which promotes the accumulation of DNA damage factors in the chromatin surrounding the break. The functional significance ...of the resulting DNA damage foci is poorly understood. Here we show that 53BP1 (also known as TRP53BP1), a component of DNA damage foci, changes the dynamic behaviour of chromatin to promote DNA repair. We used conditional deletion of the shelterin component TRF2 (also known as TERF2) from mouse cells (TRF2fl/-) to deprotect telomeres, which, like double-strand breaks, activate the ATM kinase, accumulate 53BP1 and are processed by non-homologous end joining (NHEJ). Deletion of TRF2 from 53BP1-deficient cells established that NHEJ of dysfunctional telomeres is strongly dependent on the binding of 53BP1 to damaged chromosome ends. To address the mechanism by which 53BP1 promotes NHEJ, we used time-lapse microscopy to measure telomere dynamics before and after their deprotection. Imaging showed that deprotected telomeres are more mobile and sample larger territories within the nucleus. This change in chromatin dynamics was dependent on 53BP1 and ATM but did not require a functional NHEJ pathway. We propose that the binding of 53BP1 near DNA breaks changes the dynamic behaviour of the local chromatin, thereby facilitating NHEJ repair reactions that involve distant sites, including joining of dysfunctional telomeres and AID (also known as AICDA)-induced breaks in immunoglobulin class-switch recombination.
Direct implementation with evidence Banerjee, Soumen; Chen, Yi‐Chun; Sun, Yifei
Theoretical economics,
20/May , Letnik:
19, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We study full implementation with evidence in an environment with bounded utilities. We show that a social choice function is Nash implementable in a direct revelation mechanism if and only if it ...satisfies the measurability condition proposed by Ben‐Porath and Lipman (2012). Building on a novel classification of lies according to their refutability with evidence, the mechanism requires only two agents, accounts for mixed‐strategy equilibria, and accommodates evidentiary costs. While monetary transfers are used, they are off the equilibrium and can be balanced with three or more agents. In a richer model of evidence due to Kartik and Tercieux (2012a), we establish pure‐strategy implementation with two or more agents in a direct revelation mechanism. We also obtain a necessary and sufficient condition on the evidence structure for renegotiation‐proof bilateral contracts, based on the classification of lies.
Summary
Ethylene influences many aspects of plant growth and development. The biosynthesis of ethylene is highly regulated by a variety of internal and external cues. A key target of this regulation ...is 1‐aminocyclopropane‐1‐carboxylic acid (ACC) synthases (ACS), generally the rate‐limiting step in ethylene biosynthesis, which is regulated both transcriptionally and post‐transcriptionally. Prior studies have demonstrated that cytokinin and brassinosteroid (BR) act as regulatory inputs to elevate ethylene biosynthesis by increasing the stability of ACS proteins. Here, we demonstrate that several additional phytohormones also regulate ACS protein turnover. Abscisic acid, auxin, gibberellic acid, methyl jasmonic acid, and salicylic acid differentially regulate the stability of ACS proteins, with distinct effects on various isoforms. In addition, we demonstrate that heterodimerization influences the stability of ACS proteins. Heterodimerization between ACS isoforms from distinct subclades results in increased stability of the shorter‐lived partner. Together, our study provides a comprehensive understanding of the roles of various phytohormones on ACS protein stability, which brings new insights into crosstalk between ethylene and other phytohormones, and a novel regulatory mechanism that controls ACS protein stability through a heterodimerization of ACS isoforms.
Significance Statement
The regulation of the protein stability of ACC synthase (ACS) is critical to control ethylene biosynthesis, and prior studies have demonstrated that cytokinin and brassinosteroids act as regulatory inputs to elevate ethylene biosynthesis by increasing the stability of a subset of ACS proteins. Here, we showed additional phytohormones also regulate ACS protein turnover. In addition, we revealed that homo‐ and heterodimerization of ACS isoform is a novel mechanism to control ACS protein stability.
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