79 research outputs found

    The Impossibility of Evil Qua Evil: Kantian Limitations on Human Immorality

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    Kant denies that evil qua evil can be an incentive to human beings. Is this a fact about what sorts of reasons human beings find interesting? Or, is it rooted entirely in Kant’s notion of human freedom? I focus on key facets of Kant’s system: human freedom, immorality and incentives. With an understanding of these concepts based in Christine Korsgaard’s reading of Kant’s moral theory, I argue that the impossibility of acting solely from evil qua evil is not rooted in human incentives and that if we were able to represent an unconditioned principle of immorality, we would have as powerful an incentive to act in accordance with it as we do to act in accordance with the categorical imperative. Finally, I argue that the impossibility of human beings’ having evil qua evil as an incentive is grounded in the limited nature of our positive conception of freedom

    Molecular Understanding and Modern Application of Traditional Medicines: Triumphs and Trials

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    Traditional medicines provide fertile ground for modern drug development, but first they must pass along a pathway of discovery, isolation, and mechanistic studies before eventual deployment in the clinic. Here, we highlight the challenges along this route, focusing on the compounds artemisinin, triptolide, celastrol, capsaicin, and curcumin

    Design and applications of bifunctional small molecules: Why two heads are better than one

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    Induction of protein−protein interactions is a daunting challenge, but recent studies show promise for small molecules that specifically bring two or more protein molecules together for enhanced or novel biological effect. The first such bifunctional molecules were the rapamycin- and FK506-based “chemical inducers of dimerization”, but the field has since expanded with new molecules and new applications in chemical genetics and cell biology. Examples include coumermycin-mediated gyrase B dimerization, proteolysis targeting chimeric molecules (PROTACs), drug hybrids, and strategies for exploiting multivalency in toxin binding and antibody recruitment. This Review discusses these and other advances in the design and use of bifunctional small molecules and potential strategies for future systems

    Benefits of Native Mycorrhizal Amendments to Perennial Agroecosystems Increases with Field Inoculation Density

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    This work is licensed under a Creative Commons Attribution 4.0 International License.Perennial polyculture cropping systems are a novel agroecological approach used to mirror some of the ecological benefits provided by native perennial ecosystems including increased carbon and nitrogen storage, more stable soils, and reduced anthropogenic input. Plants selected for perennial agroecosystems are often closely related to native perennials known to be highly dependent on microbiome biota, such as arbuscular mycorrhizal (AM) fungi. However, most plantings take place in highly disturbed soils where tillage and chemical use may have rendered the AM fungal communities less abundant and ineffective. Studies of mycorrhizal amendments include inoculation densities of 2–10,000 kg of inocula per hectare. These studies report variable results that may depend on inocula volume, composition, or nativeness. Here, we test the response of 19 crop plant species to a native mycorrhizal fungal community in a greenhouse and field experiment. In our field experiment, we chose eight different densities of AM fungal amendment, ranging from 0 to 8192 kg/hectare, representing conventional agricultural practices (no AM fungi addition), commercial product density recommendations, and higher densities more typical of past scientific investigation. We found that plant species that benefited from native mycorrhizal inocula in the greenhouse also benefited from inoculation in the field polyculture planting. However, the densities of mycorrhizal inocula suggested on commercial mycorrhizal products were ineffective, and higher concentrations were required to detect significant benefit plant growth and survival. These data suggest that higher concentrations of mycorrhizal amendment or perhaps alternative distribution methods may be required to utilize native mycorrhizal amendment in agroecology systems.Perennial Agricultural ProjectNational Science Foundation (DEB-1556664, DEB-1738041, OIA 1656006)USDA (grant 2016-67011-25166

    Triptolide Directly Inhibits dCTP Pyrophosphatase

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    Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti-inflammatory, antifertility, and antipolycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide-interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide

    Progress and bottlenecks in the early domestication of the perennial oilseed Silphium integrifolium, a sunflower substitute

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    Silflower (Silphium integrifolium Michx.) is in the early stages of domestication as a perennial version of oilseed sunflower, its close relative. Grain crops with deep perennial root systems will provide farmers with new alternatives for managing soil moisture and limiting or remediating soil erosion, fertilizer leaching, and loss of soil biota. Several cycles of selection for increased seed production potential following initial germplasm evaluation in 2002 have provided opportunities to document the botany and ecology of this relatively obscure species, to compare agronomic practices for improving its propagation and management, and to evaluate the differences between semi-domesticated and wild accessions that have accrued over this time through intentional and unintentional genetic processes. Key findings include: domestication has increased aboveground biomass at seedling and adult stages; seed yield has increased more, achieving modest improvement in harvest index. Harvest index decreases with nitrogen fertilization. Silflower acquires nitrogen and water from greater depth than typical crops. In agricultural silflower stands within its native range, we found that Puccinia silphii (rust) and Eucosma giganteana (moth) populations build up to unacceptable levels, but we also found genetic variation for traits contributing to resistance or tolerance. Breeding or management for reduced height and vegetative plasticity should be top priorities for future silflower research outside its native range.Fil: Vilela, Alejandra Elena. Museo Paleontológico Egidio Feruglio; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González Paleo, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Turner, Kathryn. The Land Institute; Estados UnidosFil: Peterson, Kelsey. The Land Institute; Estados UnidosFil: Ravetta, Damián Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Crews, Timothy E.. The Land Institute; Estados UnidosFil: Van Tassel, David. The Land Institute; Estados Unido

    Community structure of soil fungi in a novel perennial crop monoculture, annual agriculture, and native prairie reconstruction

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    The use of perennial crop species in agricultural systems may increase ecosystem services and sustainability. Because soil microbial communities play a major role in many processes on which ecosystem services and sustainability depend, characterization of soil community structure in novel perennial crop systems is necessary to understand potential shifts in function and crop responses. Here, we characterized soil fungal community composition at two depths (0–10 and 10–30 cm) in replicated, long-term plots containing one of three different cropping systems: a tilled three-crop rotation of annual crops, a novel perennial crop monoculture (Intermediate wheatgrass, which produces the grain Kernza®), and a native prairie reconstruction. The overall fungal community was similar under the perennial monoculture and native vegetation, but both were distinct from those in annual agriculture. The mutualist and saprotrophic community subsets mirrored differences of the overall community, but pathogens were similar among cropping systems. Depth structured overall communities as well as each functional group subset. These results reinforce studies showing strong effects of tillage and sampling depth on soil community structure and suggest plant species diversity may play a weaker role. Similarities in the overall and functional fungal communities between the perennial monoculture and native vegetation suggest Kernza® cropping systems have the potential to mimic reconstructed natural systems

    Nitrate leaching losses and the fate of 15N fertilizer in perennial intermediate wheatgrass and annual wheat — A field study

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    Perennial grains, such as the intermediate wheatgrass (Thinopyrum intermedium) (IWG), may reduce negative environmental effects compared to annual grain crops. Their permanent, and generally larger, root systems are likely to retain nitrogen (N) better, decreasing harmful losses of N and improving fertilizer N use efficiency, but there have been no comprehensive N fertilizer recovery studies in IWG to date. We measured fertilizer N recovery with stable isotope tracers in crop biomass and soil, soil N mineralization and nitrification, and nitrate leaching in IWG and annual wheat in a replicated block field experiment. Nitrate leaching was drastically reduced in IWG (0.1 and 3.1 kg N ha−1 yr−1) in its third and fourth year since establishment, compared with 5.6 kg N ha−1 yr−1 in annual wheat and 41.0 kg N ha−1 yr−1 in fallow respectively. There were no differences in net N mineralization or nitrification between IWG and annual wheat, though there was generally more inorganic N in the soil profile of annual wheat. More 15N fertilizer was recovered in the straw and all depths of the roots and soils in IWG than annual wheat. However, annual wheat recovered much more 15N fertilizer in the seeds compared to IWG, which had lower grain yields. 15N-labeled fertilizer contributed little

    Assessing impacts of alternative livestock management practices: raging debates and a role for science

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    Grazing of domestic livestock is the most pervasive and persistent human impact on the grasslands and shrublands of the Colorado Plateau. Impacts on ecosystem function and biological diversity arc thought to be great, but few studies have attempted to characterize such effects and compare the impacts of alternative livestock management practices. The dearth of pertinent, defensible information has contributed to the polarization of ranching and environmental interests, and has exacerbated what is one of the most contentious social issues in the southwestern USA. We discuss the role of ecological science in deriving and disseminating information that will help focus and perhaps resolve the impasse over grazing impacts and other natural resource issues. Specifically, we describe results of our involvement in "management teams" that include ranchers, environmentalists, public servants, and interested citizens, and how this collaborative process has helped shape an experimental research program that would be impossible to execute without the involvement of divergent interests in the grazing debate. Claims of various interest groups are reformulated as testable hypotheses, and a research design is presented
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