Multiferroic films are increasingly being studied for applications in solar energy conversion because of their efficient ferroelectric polarization-driven carrier separation and above-bandgap ...generated photovoltages, which in principle can lead to energy conversion efficiencies beyond the maximum value (34%) reported in traditional silicon-based bipolar heterojunction solar cells. However, the efficiency reported so far is still too low (<2%) to be considered for commercialization. Here, we demonstrate a new approach to effectively tune the bandgap of double perovskite multiferroic oxides by engineering the cationic ordering for the case of Bi sub(2)FeCrO sub(6). Using this approach, we report a power conversion efficiency of 8.1% under AM 1.5G irradiation (100mWcm super(-2)) for Bi sub(2)FeCrO sub(6) thin-film solar cells in a multilayer configuration.
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin ...cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1. The HDAC9-MALAT1-BRG1 complex binds chromatin and represses contractile protein gene expression in association with gain of histone H3-lysine 27 trimethylation modifications. Disruption of Malat1 or Hdac9 restores contractile protein expression, improves aortic mural architecture, and inhibits experimental aneurysm growth. Thus, we highlight a shared epigenetic pathway responsible for VSMC dysfunction in both forms of TAA, with potential therapeutic implication for other known HDAC9-associated vascular diseases.
Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions ...between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta.
MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis.
Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury.
Summary
The marked trend and consumers growing interest in natural and healthy products have forced researches and industry to develop novel products with functional ingredients. Microalgae have been ...recognized as source of functional ingredients with positive health effects since these microorganisms produce polyunsaturated fatty acids, polysaccharides, natural pigments, essential minerals, vitamins, enzymes and bioactive peptides. For this reason, the manuscript reviews two of the main high‐value metabolites which can be obtained from microalgae: pigments and essential lipids. Therefore, the extraction and purification methods for polyunsaturated fatty acids, astaxanthin, phycoerythrin and phycocyanin are described. Also, the effect that environmental growth conditions have in the production of these metabolites is described. This review summarizes the existing methods to extract and purify such metabolites in order to develop a feasible and sustainable algae industry.
This article based on literature framework describes lipids and pigments as two representative classes of high value compounds synthesized by algae.In the case of lipids, metabolic production, extraction and quantification methods are discussed. For pigments, the extraction and purification methods for astaxanthin, phycocyanin and phycoerytrin are described.
There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 ...drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.
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•3,000 compounds screened in two cell types against SARS-CoV-2•Entry pathways are distinct in hepatocyte Huh7.5 and respiratory Calu-3 cells•Only nine compounds that are active in Huh7.5 cells are active in Calu-3 cells•Cyclosporin and cyclophilin inhibitors block SARS-CoV-2 infection in diverse cells
There is an urgent need for antivirals to treat the newly emerged SARS-CoV-2. Dittmar et al. find nine host-directed drugs are antiviral in respiratory cells, seven of which have been given to humans, and three are FDA approved. We show host targets that have the potential for rapid clinical implementation.
Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro and for therapeutic cell transplantation. Despite their potential, current ...protocols to grow these organoids almost exclusively depend on culture within 3D Matrigel, which limits defined culture conditions, introduces animal components, and results in heterogenous organoids (i.e., shape, size, composition). Here, a method is described that relies on hyaluronic acid hydrogels for the generation and expansion of lung alveolar organoids (alveolospheres). Using synthetic hydrogels with defined chemical and physical properties, human‐induced pluripotent stem cell (iPSC)‐derived alveolar type 2 cells (iAT2s) self‐assemble into alveolospheres and propagate in Matrigel‐free conditions. By engineering predefined microcavities within these hydrogels, the heterogeneity of alveolosphere size and structure is reduced when compared to 3D culture, while maintaining the alveolar type 2 cell fate of human iAT2‐derived progenitor cells. This hydrogel system is a facile and accessible system for the culture of iPSC‐derived lung progenitors and the method can be expanded to the culture of primary mouse tissue derived AT2 and other epithelial progenitor and stem cell aggregates.
Epithelial cell organoids provide a system to probe tissue development and disease in vitro and for cell transplantation. Within the lung field, alveolar organoids almost exclusively depend on Matrigel, which limits defined culture conditions. In this work, the design of an accessible hydrogel system with predefined microcavities to generate alveolar organoids through self‐assembly and maintenance of progenitor cell fate and function is described.
The regulation of gene expression in cells, including by microRNAs (miRNAs), is a dynamic process. Current methods for identifying miRNA targets by combining sequence and miRNA and mRNA expression ...data do not adequately use the temporal information and thus miss important miRNAs and their targets. We developed the MIRna Dynamic Regulatory Events Miner (mirDREM), a probabilistic modeling method that uses input–output hidden Markov models to reconstruct dynamic regulatory networks that explain how temporal gene expression is jointly regulated by miRNAs and transcription factors. We measured miRNA and mRNA expression for postnatal lung development in mice and used mirDREM to study the regulation of this process. The reconstructed dynamic network correctly identified known miRNAs and transcription factors. The method has also provided predictions about additional miRNAs regulating this process and the specific developmental phases they regulate, several of which were experimentally validated. Our analysis uncovered links between miRNAs involved in lung development and differentially expressed miRNAs in idiopathic pulmonary fibrosis patients, some of which we have experimentally validated using proliferation assays. These results indicate that some disease progression pathways in idiopathic pulmonary fibrosis may represent partial reversal of lung differentiation.
Urine patches and dung pats from grazing livestock create hotspots for production and emission of the greenhouse gas, nitrous oxide (N2O), and represent a large proportion of total N2O emissions in ...many national agricultural greenhouse gas inventories. As such, there is much interest in developing country specific N2O emission factors (EFs) for excretal nitrogen (EF3, pasture, range and paddock) deposited during gazing. The aims of this study were to generate separate N2O emissions data for cattle derived urine and dung, to provide an evidence base for the generation of a country specific EF for the UK from this nitrogen source. The experiments were also designed to determine the effects of site and timing of application on emissions, and the efficacy of the nitrification inhibitor, dicyandiamide (DCD) on N2O losses. This co-ordinated set of 15 plot-scale, year-long field experiments using static chambers was conducted at five grassland sites, typical of the soil and climatic zones of grazed grassland in the UK. We show that the average urine and dung N2O EFs were 0.69% and 0.19%, respectively, resulting in a combined excretal N2O EF (EF3), of 0.49%, which is <25% of the IPCC default EF3 for excretal returns from grazing cattle. Regression analysis suggests that urine N2O EFs were controlled more by composition than was the case for dung, whilst dung N2O EFs were more related to soil and environmental factors. The urine N2O EF was significantly greater from the site in SW England, and significantly greater from the early grazing season urine application than later applications. Dycandiamide reduced the N2O EF from urine patches by an average of 46%. The significantly lower excretal EF3 than the IPCC default has implications for the UK's national inventory and for subsequent carbon footprinting of UK ruminant livestock products.
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•First co-ordinated experiments in UK to generate data for country specific grazing excretal N2O EF•Urine had a significantly greater average N2O EF (0.69%) than dung (0.19%).•The combined excretal N2O EF was 0.49%, <25% of the IPCC default value for cattle.•DCD reduced the N2O EF from urine patches by an average of 46%.•Urine N2O was controlled by its composition, dung N2O was related to soil and environmental factors.
•N2O EFs from urine deposition to grassland are larger if applied in spring.•Meta-analysis showed a significant effect of season and not of treatment on the N2O EFs.•Methane emissions were larger ...from the dung application compared to urine.•CH4 totals were significantly different across seasons (lowest in spring).•CH4 totals were not significantly different between treatments.
Emissions of nitrous oxide (N2O) from soils from grazed grasslands have large uncertainty due to the great spatial variability of excreta deposition, resulting in heterogeneous distribution of nutrients. The contribution of urine to the labile N pool, much larger than that from dung, is likely to be a major source of emissions so efforts to determine N2O emission factors (EFs) from urine and dung deposition are required to improve the inventory of greenhouse gases from agriculture. We investigated the effect of the application of cattle urine and dung at different times of the grazing season on N2O emissions from a grassland clay loam soil. Methane emissions were also quantified. We assessed the effect of a nitrification inhibitor, dicyandiamide (DCD), on N2O emissions from urine application and also included an artificial urine treatment. There were significant differences in N2O EFs between treatments in the spring (largest from urine and lowest from dung) but not in the summer and autumn applications. We also found that there was a significant effect of season (largest in spring) but not of treatment on the N2O EFs. The resulting EF values were 2.96, 0.56 and 0.11% of applied N for urine for spring, summer and autumn applications, respectively. The N2O EF values for dung were 0.14, 0.39 and 0.10% for spring, summer and autumn applications, respectively. The inhibitor was effective in reducing N2O emissions for the spring application only. Methane emissions were larger from the dung application but there were no significant differences between treatments across season of application.
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