398 research outputs found

    Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

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    A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary KD values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo

    A comparative state-level analysis of carbon capture and storage (CCS) discourse among U.S. energy stakeholders and the public

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    AbstractPerceptions of the potential of emerging technologies like carbon capture and storage (CCS) are constructed not just through technical and economic processes but also through discourse, i.e. through compelling narratives about what a technology is, what a technology might become and why it is needed and preferable to competing technologies. The influence of discourse is particularly important in the innovation phases prior to commercialization when innovation activities are focused on research, development and demonstration, and when feasibility and costs of alternatives systems cannot yet be tested by market dynamics. This paper provides a state-level comparative analysis of CCS discourse in the U.S. to provide insights about the socio-political context in which CCS technology is advancing and being considered in four different states: Massachusetts, Minnesota, Montana, and Texas. This research combines analysis of interviews of state-level energy stakeholders and media analysis of state-level newspapers. In semi-structured interviews, state-level energy policy stakeholders were asked to explain their perceptions of the potential opportunities and risks of CCS technology within their unique state context. Interview texts were coded to assess the frequency and extent of various different frames of CCS opportunities and risks including technical, political, economic, environmental, aesthetic, and health/safety. A similar coding scheme was applied to analysis of state-level newspaper coverage of CCS technology. Here, the frequency of these different framings of CCS opportunities and risks in state-level print media was assessed. This analysis demonstrates wide variation in state-level CCS discourse and perceptions of the potential opportunities and risks associated with CCS technology. This mixed-methods approach to characterizing the socio-political context for CCS advancement in these four states contributes to improved understanding of state-level variation in energy technology innovation, provides valuable information about energy technology development in these specific states, and also offers insight into the very different sub-national discourses associated with emerging low-carbon energy technologies in the U.S

    Design Thinking for the Applied Sciences: Developing a Novel Approach to Encourage the Use of Synthetic Aperture Radar (SAR) and Open Source Tools for Forest Monitoring

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    Earth observations from Synthetic Aperture Radar, or SAR, have yet to be fully leveraged for forest monitoring applications. While SAR sensors are uniquely able to capture components of forest structure over optical imagery, especially in cloud-heavy regions, there is a shortage of freely-available applied training materials and related case studies. With the wealth of available datasets from Sentinel-1 and other missions, such as ALOS-Palsar open historical archive, and in preparation for upcoming opendata policy SAR missions (e.g. NISAR and BIOMASS), the applied forestry community would benefit from increased access to relevant, understandable SAR training materials. This work documents lessons learned and best practices for creating EO capacity building/training materials gleaned from the SAR Handbook project. Strategies for increasing legibility for both print and online applications, illustration and editing guidelines for original and modified figures, and the development of quick-reference guides will be shared. Additionally, the conception and use of companion explainer videos, using cartoon characters and humor to outline relevant SAR concepts will be explored. Preliminary results indicate the SAR Handbook and supplemental project materials are already having an impact in training sessions. Increased uptake of SAR technologies in SERVIR Hub regions, where Hubs are leading follow-on SAR trainings, has also been noted. In addition, a review of download statistics from the SERVIR global website indicates widespread worldwide access. We conclude similar holistic approaches integrating design concepts into future content development would help increase uptake of EO applications by the earth science community

    Lessons Learned from the First 10 Years of the Oaks and Prairies Joint Venture’s Grassland Restoration Incentive Program (GRIP)

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    The Oaks and Prairies Joint Venture (OPJV) was formed in 2008 as a public-private partnership of agencies and organizations working across jurisdictional boundaries in portions of Texas and Oklahoma, USA. The OPJV’s major focus is reversing declines of bird populations by supporting strategic habitat conservation (biological planning, conservation design, conservation delivery, mission-based monitoring, and assumption-driven research) for northern bobwhite (Colinus virginianus), grasslandobligate species, and their respective habitats. Our objective for this paper is to document and share a decade of lessons learned in developing a partnership-based native grassland conservation program to meet grassland bird conservation targets. We share lessons learned about how to manage partnership-based, large-scale habitat incentive programs to better target project locations and habitat practice types. To establish initial shared purpose, OPJV partners drew from population and habitat objectives in various state, national, and international bird conservation plans, stepped down to ecoregion levels, to establish the OPJV Grassland Bird Conservation Business Plan. The plan has 4 strategies directly contributing to the achievement of OPJV grassland bird biological objectives that are directly supported by OPJV staff or resources (or both). The overall objective for 2015–2025 was 619,978 ha (1,532,000 acres) improved within 40 focal counties, representing 1/3 of all counties in the OPJV. Our main strategy was to provide financial incentives through the OPJV Grassland Restoration Incentive Program (GRIP) to private landowners for conducting beneficial grassland bird habitat management practices. Since inception in 2013, GRIP has treated over 44,515 ha (110,000 acres) on private lands in Texas and Oklahoma, with the goal of maintaining highquality grassland bird habitat on treated hectares for ≥5 years. In 2017, OPJV partners working with USDA Natural Resources Conservation Service, began a 5-year, $6.1 million partnership to provide additional technical and financial assistance to private landowners interested in grassland conservation through the Regional Conservation Partnership Program (RCPP). A project scoring system was designed to strategically encourage individual projects to include prescribed fire—one of the lowest cost practices per hectare—as a recurring practice to maintain program-achieved grassland improvements. Post-inception of the RCPP, the area treated with prescribed fire increased from approximately 809 ha (2,000 acres)/year to 3,237 ha (8,000 acres)/ year, while maintaining average annual hectares of all other beneficial practices. Beginning in 2013, bird point count surveys were conducted annually to monitor northern bobwhite and grassland bird populations, including a subset of points under the National Bobwhite Conservation Initiative (NBCI) Coordinated Implementation Plan. To date, nearly 25,000 individual point counts have been performed in Texas (n = 20,111) and Oklahoma (n = 4,558). Working together, OPJV partners have made significant progress toward meeting grassland bird habitat and population objectives, while tracking progress and improving methods. However, there is still considerable work ahead

    First Evidence for Adoption in California Sea Lions

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    Demographic parameters such as birth and death rates determine the persistence of populations. Understanding the mechanisms that influence these rates is essential to developing effective management strategies. Alloparental behavior, or the care of non-filial young, has been documented in many species and has been shown to influence offspring survival. However, the role of alloparental behavior in maintaining population viability has not been previously studied. Here, we provide the first evidence for adoption in California sea lions and show that adoption potentially works to maintain a high survival rate of young and may ultimately contribute to population persistence. Alloparental behavior should have a positive effect on the population growth rate when the sum of the effects on fitness for the alloparent and beneficiary is positive

    Hsp90 governs dispersion and drug resistance of fungal biofilms

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    Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

    Systems analysis of auxin transport in the Arabidopsis root apex

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    Auxin is a key regulator of plant growth and development. Within the root tip, auxin distribution plays a crucial role specifying developmental zones and coordinating tropic responses. Determining how the organ-scale auxin pattern is regulated at the cellular scale is essential to understanding how these processes are controlled. In this study, we developed an auxin transport model based on actual root cell geometries and carrier subcellular localizations. We tested model predictions using the DII-VENUS auxin sensor in conjunction with state-of-the-art segmentation tools. Our study revealed that auxin efflux carriers alone cannot create the pattern of auxin distribution at the root tip and that AUX1/LAX influx carriers are also required. We observed that AUX1 in lateral root cap (LRC) and elongating epidermal cells greatly enhance auxin’s shootward flux, with this flux being predominantly through the LRC, entering the epidermal cells only as they enter the elongation zone. We conclude that the nonpolar AUX1/LAX influx carriers control which tissues have high auxin levels, whereas the polar PIN carriers control the direction of auxin transport within these tissues

    Testing Human Sperm Chemotaxis: How to Detect Biased Motion in Population Assays

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    Biased motion of motile cells in a concentration gradient of a chemoattractant is frequently studied on the population level. This approach has been particularly employed in human sperm chemotactic assays, where the fraction of responsive cells is low and detection of biased motion depends on subtle differences. In these assays, statistical measures such as population odds ratios of swimming directions can be employed to infer chemotactic performance. Here, we report on an improved method to assess statistical significance of experimentally determined odds ratios and discuss the strong impact of data correlations that arise from the directional persistence of sperm swimming
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