52 research outputs found

    Joy leads to overconfidence, and a simple countermeasure

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    Overconfidence has been identified as a source of suboptimal decision making in many real-life domains, with often far-reaching consequences. This study identifies a mechanism that can cause overconfidence and demonstrates a simple, effective countermeasure in an incentive-compatible experimental study. We observed that joy induced overconfidence if the reason for joy (an unexpected gift) was u

    Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

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    We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies

    Protein/DNA interactions in complex DNA topologies: expect the unexpected

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    DNA supercoiling results in compacted DNA structures that can bring distal sites into close proximity. It also changes the local structure of the DNA, which can in turn influence the way it is recognised by drugs, other nucleic acids and proteins. Here, we discuss how DNA supercoiling and the formation of complex DNA topologies can affect the thermodynamics of DNA recognition. We then speculate on the implications for transcriptional control and the three-dimensional organisation of the genetic material, using examples from our own simulations and from the literature. We introduce and discuss the concept of coupling between the multiple length-scales associated with hierarchical nuclear structural organisation through DNA supercoiling and topology

    A recent volcanic eruption beneath the West Antarctic ice sheet

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    Indirect evidence suggests that volcanic activity occurring beneath the West Antarctic ice sheet influences ice flow and sheet stability(1-3). However, only volcanoes that protrude through the ice sheet(4) and those inferred from geophysical techniques(1,2) have been mapped so far. Here we analyse radar data from the Hudson Mountains, West Antarctica(5), that contain reflections from within the ice that had previously been interpreted erroneously as the ice-sheet bed. We show that the reflections are present within an elliptical area of about 23,000km(2) that contains tephra from an explosive volcanic eruption. The tephra layer is thickest at a subglacial topographic high, which we term the Hudson Mountains Subglacial Volcano. The layer depth dates the eruption at 207 BC +/- 240 years, which matches exceptionally strong but previously unattributed conductivity signals in nearby ice cores. The layer contains 0.019 - 0.31 km(3) of tephra, which implies a volcanic explosive index of 3-4. Production and episodic release of water from the volcano probably affected ice flow at the time of the eruption. Ongoing volcanic heat production may have implications for contemporary ice dynamics in this glacial system

    Transgenic alfalfa secretes a fungal endochitinase protein to the rhizosphere

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    Transgenic plants containing a chimeric gene construct that facilitates the exudation of proteins from roots offer novel approaches for modification of the rhizosphere and production of relatively pure recombinant proteins. The aim of this study was to develop alfalfa (Medicago sativa L.) plants that exude a heterologous recombinant protein into the rhizosphere. Alfalfa transformed with a fungal endochitinase (ech42) cDNA fused in frame to the signal peptide of a white lupin acid phosphatase and under the control of the cassava vein mosaic virus (CsVMV) promoter expressed increased chitinase activity in vegetative organs and root exudates. Chitinase activity in root exudates of transgenic alfalfa was 7.5–25.7 times higher than in the untransformed Regen-SY plants. Chitinase enzyme activity was accompanied by increased synthesis of mRNA and protein in transformed plants. By comparison, untransformed and vector only transformed plants displayed no expression of recombinant protein and mRNA. A single band of the expected molecular weight was present only in western blots of root exudates of transgenic alfalfa plants. The secreted endochitinase enzyme not only retained its lytic activity against glycol chitin but also showed antifungal activity by inhibition of spore germination of two fungal pathogens. Exudation of recombinant proteins from roots may offer alternative uses for alfalfa in the production of value-added biopharmaceuticals and may influence microbes or modify soil nutrient availability near plant roots.Mesfin Tesfaye, Matthew D. Denton, Deborah A. Samac & Carroll P. Vanc
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