823 research outputs found

    Stratigraphy of the Lower Atoka Formation, Crawford County, Arkansas

    Get PDF
    The Atoka Formation (Pennsylvanian) of northwestern Arkansas is a complex succession of sandstone and shale units. Sandstone units in surface sections near the base of the formation in northern Crawford and southern Washington Counties may be correlated with units in the subsurface of the Arkoma Basin. The basal sandstone units of the Atoka Formation as recognized in the Arkoma Basin are correlated with thin, discontinuous sandstones within the Trace Creek Member of the Bloyd Formation in surface exposures to the north. Vertical grain size profiles, electric log profiles and the configuration of thickness trends suggest that lower Atoka sandstone units accumulated as linear coastal sand bodies that prograded southeastward

    Interleukin‐5 drives glycolysis and reactive oxygen species‐dependent citric acid cycling by eosinophils

    Get PDF
    Introduction Eosinophils have been long implicated in antiparasite immunity and allergic diseases and, more recently, in regulating adipose tissue homeostasis. The metabolic processes that govern eosinophils, particularly upon activation, are unknown. Methods Peripheral blood eosinophils were isolated for the analysis of metabolic processes using extracellular flux analysis and individual metabolites by stable isotope tracer analysis coupled to gas chromatography‐mass spectrometry following treatment with IL‐3, IL‐5 or granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Eosinophil metabolism was elucidated using pharmacological inhibitors. Results Human eosinophils engage a largely glycolytic metabolism but also employ mitochondrial metabolism. Cytokine stimulation generates citric acid cycle (TCA) intermediates from both glucose and glutamine revealing this previously unknown role for mitochondria upon eosinophil activation. We further show that the metabolic programme driven by IL‐5 is dependent on the STAT5/PI3K/Akt signalling axis and that nicotinamide adenine dinucleotide phosphate oxidase (NOX)‐dependent ROS production might be a driver of mitochondrial metabolism upon eosinophil activation. Conclusion We demonstrate for the first time that eosinophils are capable of metabolic plasticity, evidenced by increased glucose‐derived lactate production upon ROS inhibition. Collectively, this study reveals a role for both glycolysis and mitochondrial metabolism in cytokine‐stimulated eosinophils. Selective targeting of eosinophil metabolism may be of therapeutic benefit in eosinophil‐mediated diseases and regulation of tissue homeostasis

    DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents

    Get PDF
    There is a long history for the bioorganic and biomedical use of N-methyl-pyrrole-derived polyamides (PAs) that are higher homologs of natural products such as distamycin A and netropsin. This work has been pursued by many groups, with the Dervan and Sugiyama groups responsible for many breakthroughs. We have studied PAs since about 1999, partly in industry and partly in academia. Early in this program, we reported methods to control cellular uptake of polyamides in cancer cell lines and other cells likely to have multidrug resistance efflux pumps induced. We went on to discover antiviral polyamides active against HPV31, where SAR showed that a minimum binding size of about 10 bp of DNA was necessary for activity. Subsequently we discovered polyamides active against two additional high-risk HPVs, HPV16 and 18, a subset of which showed broad spectrum activity against HPV16, 18 and 31. Aspects of our results presented here are incompatible with reported DNA recognition rules. For example, molecules with the same cognate DNA recognition properties varied from active to inactive against HPVs. We have since pursued the mechanism of action of antiviral polyamides, and polyamides in general, with collaborators at NanoVir, the University of Missouri-St. Louis, and Georgia State University. We describe dramatic consequences of ÎČ-alanine positioning even in relatively small, 8-ring polyamides; these results contrast sharply with prior reports. This paper was originally presented by JKB as a Keynote Lecture in the 2nd International Conference on Medicinal Chemistry and Computer Aided Drug Design Conference in Las Vegas, NV, October 2013

    The genotype of barley cultivars influences multiple aspects of their associated microbiota via differential root exudate secretion

    Get PDF
    Plant-associated microbes play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley (Hordeum vulgare) cultivars. Distinct differences were observed between the plant-associated microbiomes of the 2 cultivars, with the plant-growth promoting rhizobacterial genus Pseudomonas substantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruited Pseudomonas populations, alongside distinct genotypic clustering by cultivar. Cultivar-driven Pseudomonas selection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and Chevallier Pseudomonas isolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assays

    Statistics of the contact network in frictional and frictionless granular packings

    Get PDF
    Simulated granular packings with different particle friction coefficient mu are examined. The distribution of the particle-particle and particle-wall normal and tangential contact forces P(f) are computed and compared with existing experimental data. Here f equivalent to F/F-bar is the contact force F normalized by the average value F-bar. P(f) exhibits exponential-like decay at large forces, a plateau/peak near f = 1, with additional features at forces smaller than the average that depend on mu. Computations of the force-force spatial distribution function and the contact point radial distribution function indicate that correlations between forces are only weakly dependent on friction and decay rapidly beyond approximately three particle diameters. Distributions of the particle-particle contact angles show that the contact network is not isotropic and only weakly dependent on friction. High force-bearing structures, or force chains, do not play a dominant role in these three dimensional, unloaded packings.Comment: 11 pages, 13 figures, submitted to PR

    An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

    Get PDF
    Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).<p></p> Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.<p></p> Results: Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.<p></p> Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.<p></p&gt

    The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

    Get PDF
    The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove
    • 

    corecore