Dry deposition is a major component of total atmospheric nitrogen deposition and thus an important source of bioavailable nitrogen to ecosystems. However, relative to wet deposition, less is known ...regarding the sources and spatial variability of dry deposition. This is in part due to difficulty in measuring dry deposition and associated deposition velocities. Passive sampling techniques offer potential for improving our understanding of the spatial distribution and sources of gaseous and aerosol N species, referred to here as dry deposition. We report dual nitrate isotopic composition (δ15N and δ18O) in actively collected dry and wet deposition across the high‐deposition region of Ohio, New York, and Pennsylvania. We also present results from initial tests to examine the efficacy of using passive nitric acid collectors as a collection medium for isotopic analysis at a site in New York. Isotopic values in actively collected dry deposition, including particulate nitrate and gaseous nitric acid, are compared with those in wet nitrate deposition and surrounding NOx emission sources. δ15N values in dry and wet fractions are highest at the westernmost sites and lowest at the easternmost sites, and stationary source NOx emissions (e.g., power plants and incinerators) appear to be the primary control on δ15N spatial variability. In contrast, δ18O values show a less consistent spatial pattern in dry deposition. Both δ15N and δ18O show strong seasonality, with higher values in winter than summer. Seasonal variations in stationary source NOx emissions appear to be the most likely explanation for seasonal variations in δ15N, whereas seasonal variations in air temperature and solar radiation indicate variable chemical oxidation pathways control δ18O patterns. Additionally, we demonstrate the utility of passive samplers for collecting the nitric acid (HNO3) component of dry deposition suitable for isotopic analysis. We observe slight differences in δ15N‐HNO3 values between simultaneous samples collected actively and passively (0.6‰). However, we observe a larger offset in δ18O values between actively and passively collected samples; the causes for this offset warrant further investigation. Nonetheless, passive sample collection represents a significant cost savings over active sampling techniques and could allow a more extensive understanding of patterns of dry deposition and associated insights to nitrogen sources across landscapes.
Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug ...testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.
We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few ...historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
Ambient air monitoring as part of the US Environmental Protection Agency's (US EPA's) Clean Air Status and Trends Network (CASTNet) currently uses filter packs to measure weekly integrated ...concentrations. The US EPA is interested in supplementing CASTNet with semi-continuous monitoring systems at select sites to characterize atmospheric chemistry and deposition of nitrogen and sulfur compounds at higher time resolution than the filter pack. The Monitor for AeRosols and GAses in ambient air (MARGA) measures water-soluble gases and aerosols at an hourly temporal resolution. The performance of the MARGA was assessed under the US EPA Environmental Technology Verification (ETV) program. The assessment was conducted in Research Triangle Park, North Carolina, from 8 September to 8 October 2010 and focused on gaseous SO2, HNO3, and NH3 and aerosol SO42-, NO3-, and NH4+. Precision of the MARGA was evaluated by calculating the median absolute relative percent difference (MARPD) between paired hourly results from duplicate MARGA units (MUs), with a performance goal of ≤ 25%. The accuracy of the MARGA was evaluated by calculating the MARPD for each MU relative to the average of the duplicate denuder/filter pack concentrations, with a performance goal of ≤ 40%. Accuracy was also evaluated by using linear regression, where MU concentrations were plotted against the average of the duplicate denuder/filter pack concentrations. From this, a linear least squares line of best fit was applied. The goal was for the slope of the line of best fit to be between 0.8 and 1.2. The MARGA performed well in comparison to the denuder/filter pack for SO2, SO42−, and NH4+, with all three compounds passing the accuracy and precision goals by a significant margin. The performance of the MARGA in measuring NO3- could not be evaluated due to the different sampling efficiency of coarse NO3- by the MUs and the filter pack. Estimates of "fine" NO3- were calculated for the MUs and the filter pack. Using this and results from a previous study, it is concluded that if the MUs and the filter pack were sampling the same particle size, the MUs would have good agreement in terms of precision and accuracy. The MARGA performed moderately well in measuring HNO3 and NH3, though neither met the linear regression slope goals. However, recommendations for improving the measurement of HNO3 and NH3 are discussed. It is concluded that SO42-, SO2, NO3-, HNO3, NH4+, and NH3 concentrations can be measured with acceptable accuracy and precision when the MARGA is operated in conjunction with the recommendations outlined in the manuscript.
Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions ...by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)- and ex-US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections.
Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management ...challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where surgical treatment would result in significant deformity. Until recently, treatment options for these patients have been limited, but increased understanding of the molecular basis of BCC has enabled potential therapies, such as hedgehog signalling pathway inhibitors, to be developed. A clear definition of advanced BCC as a distinct disease entity and formal management guidelines have not previously been published, presumably because of the rarity, heterogeneity and lack of treatment options available for the disease. Here we provide a UK perspective from a multidisciplinary group of experts involved in the treatment of complex cases of BCC, addressing the key challenges associated with the perceived definition and management of the disease. With new treatments on the horizon, we further propose a definition for advanced BCC that may be used as a guide for healthcare professionals involved in disease diagnosis and management.
The Miocene Climatic Optimum (MCO, 14-17 Ma) was ~3-4 °C warmer than present, similar to estimates for 2100. Coincident with the MCO is the Monterey positive carbon isotope (δ
C) excursion, with ...oceans more depleted in
C relative to
C than any time in the past 50 Myrs. The long-standing Monterey Hypothesis uses this excursion to invoke massive marine organic carbon burial and draw-down of atmospheric CO
as a cause for the subsequent Miocene Climate Transition and Antarctic glaciation. However, this hypothesis cannot explain the multi-Myr lag between the δ
C excursion and global cooling. We use planktic foraminiferal B/Ca, δ
B, δ
C, and Mg/Ca to reconstruct surface ocean carbonate chemistry and temperature. We propose that the MCO was associated with elevated oceanic dissolved inorganic carbon caused by volcanic degassing, global warming, and sea-level rise. A key negative feedback of this warm climate was the organic carbon burial on drowned continental shelves.
Abstract
Internationally, the environmental damage caused by the improper disposal of approximately 100 Mt of plastic waste per annum is of growing concern. Attempts to address this issue have ...generated many hundreds of scientific studies announcing the discovery of novel plastic-degrading microorganisms and their respective enzymes. On closer inspection, however, evidence remains sparse for the microbial degradation of most of the plastic polymers produced globally. We systematically surveyed the international literature to confirm how many microorganisms proposed to degrade plastics (
n
= 664) cause substantial (i.e. ⩾20% mass) losses of virgin polymer, rather than losses of plastic additives, filler, and/or shedding of polymer micro-fragments. We noted where degradation was only demonstrated for artificially aged polymer since physicochemical ageing procedures increase the abundance of monomers and oligomers such that they may be degraded by microbial activity. Additionally, artificial ageing may introduce functional groups to the polymer backbone, creating more locations susceptible to microbial degradation than would otherwise occur in the environment. We identified multiple studies demonstrating the effective microbial degradation of heterochain plastic polymers such as polylactic acid, polycaprolactone and polyethylene terephthalate (i.e. polymers containing elements other than carbon in the backbone structure). However, in the literature, we find no evidence for the substantial degradation of unadulterated polyethylene, polypropylene, polystyrene or polyvinyl chloride, homochain polymers which represent the overwhelming majority of global plastics production. Current research demonstrates that the pre-treatment of plastics with elevated temperature or UV-light may speed physicochemical plastic degradation, with valuable applications for downstream microbial processing. However, evidence for the microbial degradation of most plastic polymers in current circulation is lacking. We outline simple criteria that should be met before announcing the microbial degradation of plastic polymers. We hope this may help to address largely unsubstantiated expectations that microorganisms can degrade many plastic polymers in
situ.
Frameworks for limiting ecosystem exposure to excess nutrients and acidity require accurate and complete deposition budgets of reactive nitrogen (Nr). While much progress has been made in developing ...total Nr deposition budgets for the U.S., current budgets remain limited by key data and knowledge gaps. Analysis of National Atmospheric Deposition Program Total Deposition (NADP/TDep) data illustrates several aspects of current Nr deposition that motivate additional research. Averaged across the continental U.S., dry deposition contributes slightly more (55%) to total deposition than wet deposition and is the dominant process (>90%) over broad areas of the Southwest and other arid regions of the West. Lack of dry deposition measurements imposes a reliance on models, resulting in a much higher degree of uncertainty relative to wet deposition which is routinely measured. As nitrogen oxide (NOx) emissions continue to decline, reduced forms of inorganic nitrogen (NHx = NH3 + NH4+) now contribute >50% of total Nr deposition over large areas of the U.S. Expanded monitoring and additional process-level research are needed to better understand NHx deposition, its contribution to total Nr deposition budgets, and the processes by which reduced N deposits to ecosystems. Urban and suburban areas are hotspots where routine monitoring of oxidized and reduced Nr deposition is needed. Finally, deposition budgets have incomplete information about the speciation of atmospheric nitrogen; monitoring networks do not capture important forms of Nr such as organic nitrogen. Building on these themes, we detail the state of the science of Nr deposition budgets in the U.S. and highlight research priorities to improve deposition budgets in terms of monitoring and flux measurements, leaf- to regional-scale modeling, source apportionment, and characterization of deposition trends and patterns.
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•Deposition budgets for inorganic nitrogen have improved over the last decade in the U.S.•Important data and knowledge gaps in monitoring and modeling of total nitrogen deposition remain.•Expanded monitoring of deposition in agricultural and urban areas is needed.•Monitoring of organic N deposition and improvement of organic N in atmospheric models is needed.•Land use specific modeled deposition estimates are needed for critical load assessments.
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