707 research outputs found

    ALMA CN Zeeman Observations of AS 209: Limits on Magnetic Field Strength and Magnetically Driven Accretion Rate

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    While magnetic fields likely play an important role in driving the evolution of protoplanetary disks through angular momentum transport, observational evidence of magnetic fields has only been found in a small number of disks. Although dust continuum linear polarization has been detected in an increasing number of disks, its pattern is more consistent with that from dust scattering than from magnetically aligned grains in the vast majority of cases. Continuum linear polarization from dust grains aligned to a magnetic field can reveal information about the magnetic field´s direction, but not its strength. On the other hand, observations of circular polarization in molecular lines produced by Zeeman splitting offer a direct measure of the line-of-sight magnetic field strength in disks. We present upper limits on the net toroidal and vertical magnetic field strengths in the protoplanetary disk AS 209 derived from Zeeman splitting observations of the CN 2-1 line. The 3σ upper limit on the net line-of-sight magnetic field strength in AS 209 is 5.0 mG on the redshifted side of the disk and 4.2 mG on the blueshifted side of the disk. Given the disk´s inclination angle, we set a 3σ upper limit on the net toroidal magnetic field strength of 8.7 and 7.3 mG for the red and blue sides of the disk, respectively, and 6.2 and 5.2 mG on the net vertical magnetic field on the red and blue sides of the disk. If magnetic disk winds are a significant mechanism of angular momentum transport in the disk, magnetic fields of a strength close to the upper limits would be sufficient to drive accretion at the rate previously inferred for regions near the protostar.Fil: Harrison, Rachel. University of Illinois at Urbana; Estados UnidosFil: Looney, L. W.. University of Illinois at Urbana; Estados UnidosFil: Stephens, I. W.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Li, Z.-Y.. University of Virginia; Estados UnidosFil: Teague, Richard. Department Of Astronomy; Estados UnidosFil: Crutcher, Richard. University of Illinois at Urbana; Estados UnidosFil: Yang, H.. Tsinghua University; ChinaFil: Cox, E. G.. Northwestern University; Estados UnidosFil: Fernandez Lopez, Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Shinnaga, H.. Kagoshima University; Japó

    Study of Xuanhuang Pill in protecting against alcohol liver disease using ultra-performance liquid chromatography/time-of-flight mass spectrometry and network pharmacology

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    IntroductionXuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.MethodsThe hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.ResultsThe current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.ConclusionIn summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease

    Attaching DNA to Nanoceria: Regulating Oxidase Activity and Fluorescence Quenching

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Applied Materials and Interfaces copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Pautler, R., Kelly, E. Y., Huang, P.-J. J., Cao, J., Liu, B., & Liu, J. (2013). Attaching DNA to Nanoceria: Regulating Oxidase Activity and Fluorescence Quenching. ACS Applied Materials & Interfaces, 5(15), 6820–6825. https://doi.org/10.1021/am4018863Cerium oxide nanoparticles (nanoceria) have recently emerged as a nanozyme with oxidase activity. In this work, we present a few important interfacial properties of nanoceria. First, the surface charge of nanoceria can be controlled not only by adjusting pH but also by adsorption of simple inorganic anions. Adsorption of phosphate and citrate gives negatively charged surface over a broad pH range. Second, nanoceria adsorbs DNA via the DNA phosphate backbone in a sequence-independent manner; DNA adsorption inhibits its oxidase activity. Other anionic polymers display much weaker inhibition effects. Adsorption of simple inorganic phosphate does not have the inhibition effect. Third, nanoceria is a quencher for many fluorophores. These discoveries provide an important understanding for further use of nanoceria in biosensor development, materials science, and nanotechnology.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

    Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

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    Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

    Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

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    BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

    Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

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    IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application

    A comparison of risk factors for mortality from heart failure in Asian and non-Asian populations: An overview of individual participant data from 32 prospective cohorts from the Asia-Pacific Region

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    Background: Most of what is known regarding the epidemiology of mortality from heart failure (HF) comes from studies within Western populations with few data available from the Asia-Pacific region where the burden of heart failure is increasing.Methods: Individual level data from 543694 (85% Asian; 36% female) participants from 32 cohorts in the Asia Pacific Cohort Studies Collaboration were included in the analysis. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality from HF were estimated separately for Asians and non-Asians for a quintet of cardiovascular risk factors: systolic blood pressure, diabetes, body mass index, cigarette smoking and total cholesterol. All analyses were stratified by sex and study.Results: During 3,793,229 person years of follow-up there were 614 HF deaths (80% Asian). The positive associations between elevated blood pressure, obesity, and cigarette smoking were consistent for Asians and non-Asians. There was evidence to indicate that diabetes was a weaker risk factor for death from HF for Asians compared with non-Asians: HR 1.26 (95% CI: 0.74-2.13) versus 3.04 (95% CI 1.76-5.25) respectively; p for interaction = 0.022. Additional adjustment for covariates did not materially change the overall associations. There was no good evidence to indicate that total cholesterol was a risk factor for HF mortality in either population.Conclusions: Most traditional cardiovascular risk factors including elevated blood pressure, obesity and cigarette smoking appear to operate similarly to increase the risk of death from HF in Asians and non-Asians populations alike. © 2014 Huxley et al.; licensee BioMed Central Ltd

    Seasonal climatic effects and feedbacks of anthropogenic heat release due to global energy consumption with CAM5

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    Anthropogenic heat release (AHR) is the heat generated in global energy consumption, which has not been considered in global climate models generally. The global high-resolution AHR from 1992 to 2013, which is estimated by using the Defense Meteorological Satellite Program (DMSP)/Operational Linescan System (OLS) satellite data, is implemented into the Community Atmosphere Model version 5 (CAM5). The seasonal climatic effects and possible feedbacks of AHR are examined in this study. The modeling results show that AHR increases the global annual mean surface temperature and land surface temperature by 0.02 ± 0.01 K (1σ uncertainty) and 0.05 ± 0.02 K (1σ uncertainty), respectively. The global climatic effect of AHR varies with season: with a stronger climatic effect in the boreal winter leading to global mean land surface temperature increases by 0.10 ± 0.01 K (1σ uncertainty). In the selected regions (40°N–60°N, 0°E–45°E) of Central and Western Europe the average surface temperature increases by 0.46 K in the boreal summer, and in the selected regions (45°N–75°N, 30°E–140°E) of northern Eurasia the average surface temperature increases by 0.83 K in the boreal winter. AHR changes the height and thermodynamic structure of the global planetary boundary layer, as well as the stability of the lower troposphere, which affects the global atmospheric circulation and low cloud fraction. In addition, at the surface both the shortwave radiation flux in the boreal summer and the down-welling longwave flux in the boreal winter change signifi- cantly, as a result of the change in low clouds caused by the effect of AHR. This study suggests a possible new mechanism of AHR effect on global climate through changing the global low-cloud fraction, which is crucial for global energy balance, by modifying the thermodynamic structure and stability of the lower troposphere. Thus this study improves our understanding of the global climate change caused by human activities
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