2,391 research outputs found

    Trypanosoma brucei PRMT1 Is a Nucleic Acid Binding Protein with a Role in Energy Metabolism and the Starvation Stress Response.

    Get PDF
    In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed to measure protein steady-state levels in cells lacking TbPRMT1. The approach revealed striking changes in proteins involved in energy metabolism. Most prominent were a decrease in glycolytic enzyme abundance and an increase in proline degradation pathway components, changes that resemble the metabolic remodeling that occurs during T. brucei life cycle progression. The work describes several RNA binding proteins whose association with mRNA was altered in TbPRMT1-depleted cells, and a large number of TbPRMT1-interacting proteins, thereby highlighting potential TbPRMT1 substrates. Many proteins involved in the T. brucei starvation stress response were found to interact with TbPRMT1, prompting analysis of the response of TbPRMT1-depleted cells to nutrient deprivation. Indeed, depletion of TbPRMT1 strongly hinders the ability of T. brucei to form cytoplasmic mRNA granules under starvation conditions. Finally, this work shows that TbPRMT1 itself binds nucleic acids in vitro and in vivo, a feature completely novel to protein arginine methyltransferases.IMPORTANCETrypanosoma brucei infection causes human African trypanosomiasis, also known as sleeping sickness, a disease with a nearly 100% fatality rate when untreated. Current drugs are expensive, toxic, and highly impractical to administer, prompting the community to explore various unique aspects of T. brucei biology in search of better treatments. In this study, we identified the protein arginine methyltransferase (PRMT), TbPRMT1, as a factor that modulates numerous aspects of T. brucei biology. These include glycolysis and life cycle progression signaling, both of which are being intensely researched toward identification of potential drug targets. Our data will aid research in those fields. Furthermore, we demonstrate for the first time a direct association of a PRMT with nucleic acids, a finding we believe could translate to other organisms, including humans, thereby impacting research in fields as distant as human cancer biology and immune response modulation. Copyright © 2018 Kafková et al

    Factors that support Indigenous involvement in multi-actor environmental stewardship

    Get PDF
    Regional, multi-actor environmental collaborations bring together diverse parties to achieve environmental protection and stewardship outcomes. Involving a range of participants helps involve alternative forms of knowledge, expertise, and perspectives; it may also present greater challenges in reaching agreements, particularly when both Indigenous and non-Indigenous parties are involved. The authors conduct a cross-case study of 39 regional partnerships involving Indigenous nations from the Great Lakes basin of North America with the aim of determining the factors that enable Indigenous partners to remain engaged in multi-actor collaborations. Six characteristics influenced Indigenous nations’ willingness to remain engaged: respect for Indigenous knowledges, control of knowledge mobilization, intergenerational involvement, self-determination, continuous cross-cultural education, and early involvement. Being attentive of these factors can help partnerships achieve their environmental goals by keeping important partners at the table

    Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses

    Get PDF
    Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\upmu\end{document}m), and can be used with idealized and experimental pulse waveforms. The model consists of traditional passive components and additional active components representing nonequilibrium processes. Model responses include measurable quantities: transmembrane voltage, membrane electrical conductance, and solute transport rates and amounts for the representative “long” and “short” pulses. The long pulse—1.5 kV/cm, 100 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\upmu\end{document}s—evolves two pore subpopulations with a valley at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}{\sim}\end{document}5 nm, which separates the subpopulations that have peaks at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}{\sim}\end{document}1.5 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}{\sim}\end{document}12 nm radius. Such pulses are widely used in biological research, biotechnology, and medicine, including cancer therapy by drug delivery and nonthermal physical tumor ablation by causing necrosis. The short pulse—40 kV/cm, 10 ns—creates 80-fold more pores, all small (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}<<\end{document}3 nm; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\sim\end{document}1 nm peak). These nanosecond pulses ablate tumors by apoptosis. We demonstrate the model’s responses by illustrative electrical and poration behavior, and transport of calcein and propidium. We then identify extensions for expanding modeling capability. Structure-function results from MD can allow extrapolations that bring response specificity to cell membranes based on their lipid composition. After a pulse, changes in pore energy landscape can be included over seconds to minutes, by mechanisms such as cell swelling and pulse-induced chemical reactions that slowly alter pore behavior. Electronic supplementary material The online version of this article (doi:10.1007/s00232-014-9699-z) contains supplementary material, which is available to authorized users

    Context-Sensitive Auto-Sanitization for PHP

    Get PDF

    Upper and lower Cottonwood and Neosho headwaters watersheds assessment: preliminary report

    Get PDF
    A.P. Nejadhashemi, et. al, Upper and Lower Cottonwood and Neosho Headwaters Watersheds Assessment: Preliminary Report, Manhattan, Kansas, Kansas State University, February 2009

    The environmental effects of crop price increases: Nitrogen losses in the U.S. Corn Belt

    Get PDF
    Citation: Hendricks, N. P., Sinnathamby, S., Douglas-Mankin, K., Smith, A., Sumner, D. A., & Earnhart, D. H. (2014). The environmental effects of crop price increases: Nitrogen losses in the U.S. Corn Belt. Journal of Environmental Economics and Management, 68(3), 507–526. https://doi.org/10.1016/j.jeem.2014.09.002High corn prices cause farmers to plant more corn on fields that were planted to corn in the previous year, rather than alternating between corn and soybeans. Cultivating corn after corn requires greater nitrogen fertilizer and some of this nitrogen flows into waterways and causes environmental damage. We estimate the effect of crop prices on nitrogen losses for most fields in Iowa, Illinois, and Indiana using crop data from satellite imagery. Spatial variation in these high-resolution estimates highlights the fact that the environmental effects of agriculture depend not only on what is grown, but also on where and in what sequence it is grown. Our results suggest that the change in corn and soybean prices due to a billion gallons of ethanol production expands the size of the hypoxic zone in the Gulf of Mexico by roughly 30 square miles on average, although there is considerable uncertainty in this estimate

    Lower Big Blue watershed assessment: preliminary report

    Get PDF
    Nejadhashemi, A.P., et. al, Lower Big Blue Watershed Assessment: Preliminary Report, Manhattan, Kansas, Kansas State University, February 2009

    Elk River watershed assessment: preliminary report

    Get PDF
    Nejadhashemi, A.P., et. al, Elk River Watershed Assessment: Preliminary Report, Manhattan, Kansas, Kansas State University, February 2009

    Milford Lake watershed assessment: preliminary report

    Get PDF
    Nejadhashemi, A.P., et. al, Milford Lake Watershed Assessment: Preliminary Report, Manhattan, Kansas, Kansas State University, February 2009
    corecore