3,790 research outputs found
Reorganization of self-assembled DNA-based polymers using orthogonally addressable building blocks
Nature uses non-covalent interactions to achieve structural dynamic reconfiguration of biopolymers. Taking advantage of the programmability of DNA/DNA interactions we report here the rational design of orthogonal DNA-based addressable tiles that self-assemble into polymer-like structures that can be reconfigured by external inputs. The different tiles share the same sticky ends responsible for self-assembly but are rationally designed to contain a specific regulator-binding domain that can be orthogonally targeted by different DNA regulator strands. We show that by sequentially adding specific inputs it is possible to re-organize the formed structures to display well-defined distributions: homopolymers, random and block structures. The versatility of the systems presented in this study shows the ease with which DNA-based addressable monomers can be designed to create reconfigurable micron-scale DNA structures offering a new approach to the growing field of supramolecular polymers
Fuel-Responsive Allosteric DNA-Based Aptamers for the Transient Release of ATP and Cocaine
We show herein that allostery offers a key strategy for the design of out-of-equilibrium systems by engineering allosteric DNA-based nanodevices for the transient loading and release of small organic molecules. To demonstrate the generality of our approach, we used two model DNA-based aptamers that bind ATP and cocaine through a target-induced conformational change. We re-engineered these aptamers so that their affinity towards their specific target is controlled by a DNA sequence acting as an allosteric inhibitor. The use of an enzyme that specifically cleaves the inhibitor only when it is bound to the aptamer generates a transient allosteric control that leads to the release of ATP or cocaine from the aptamers. Our approach confirms that the programmability and predictability of nucleic acids make synthetic DNA/RNA the perfect candidate material to re-engineer synthetic receptors that can undergo chemical fuel-triggered release of small-molecule cargoes and to rationally design non-equilibrium systems
Directions for the design of energy efficient kinematics in adaptive solar building envelopes
The development of adaptive building envelopes is receiving increasing interest in contemporary architecture, as it strives to cope with several requirements such as energy saving and harvesting (or mitigating environmental actions), improving performance and, finally, aesthetics. Actual implementation fundamentally concerns external “skins” (i.e. adaptive façades), but internal “skins” (e.g. adaptive ceilings) may also be developed.
The engineering aspects related to the above developments are quite complex and involve different behavioral models to be merged within the adaptive strategy.
In the present paper, a study is presented that concerns the conception of an adaptive origami-like solar skin. The main design issues in managing the kinematics of the envelope are then identified and the envisaged solutions, to be developed in the next stage of the research, are discussed
Why future nitrogen research needs the social sciences
Nitrogen management is on the cusp of becoming a major global policy issue — the international community is gradually acknowledging that the feasibility of an array of environmental, health and food security goals hinges on how humanity manages nitrogen as a resource and a pollutant over the coming decades. As a result, the nitrogen research agenda should expand to consider more policy-relevant questions, such as the power dynamics of the broader food system and the many influences on farmer decision-making. Doing so demands much closer collaboration between the natural and social sciences, from problem formulation to research execution, which requires overcoming a range of ideological, institutional and knowledge barriers
Spontaneous reorganization of DNA-based polymers in higher ordered structures fueled by RNA
We demonstrate a strategy that allows for the spontaneous reconfiguration of self-assembled DNA polymers exploiting RNA as chemical fuel. To do this, we have rationally designed orthogonally addressable DNA building blocks that can be transiently deactivated by RNA fuels and subtracted temporarily from participation in the self-assembly process. Through a fine modulation of the rate at which the building blocks are reactivated we can carefully control the final composition of the polymer and convert a disordered polymer in a higher order polymer, which is disfavored from a thermodynamic point of view. We measure the dynamic reconfiguration via fluorescent signals and confocal microscopy, and we derive a kinetic model that captures the experimental results. Our approach suggests a novel route toward the development of biomolecular materials in which engineered chemical reactions support the autonomous spatial reorganization of multiple components
Quantification of the Chemical Chaperone 4-Phenylbutyric Acid (4-PBA) in Cell Culture Media via LC-HRMS: Applications in Fields of Neurodegeneration and Cancer
In recent years, 4-phenylbutyric acid (4-PBA), an FDA-approved drug, has increasingly been used as a nonspecific chemical chaperone in vitro and in vitro, but its pharmacodynamics is still not clear. In this context, we developed and validated a Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS) method to quantify 4-PBA in NeuroBasal-A and Dulbecco’s Modified Eagle widely used cell culture media. Samples were injected on a Luna® 3 µm PFP(2) 100 Å (100 × 2.0 mm) column maintained at 40 °C. Water and methanol both with 0.1% formic acid served as mobile phases in a step gradient mode. The mass acquisition was performed by selected ion monitoring (SIM) in negative mode for a total run time of 10.5 min at a flow rate of 0.300 mL/min. The analogue 4-(4-Nitrophenyl)-Butyric Acid served as internal standard. Validation parameters were verified according to FDA and EMA guidelines. The quantification ranges from 0.38–24 µM. Inter and intraday RSDs (Relative Standard Deviations) were within 15%. The developed LC-HRMS method allowed the estimation of 4-PBA absorption and adsorption kinetics in vitro in two experimental systems: (i) 4-PBA improvement of protein synthesis in an Alzheimer’s disease astrocytic cell model; and (ii) 4-PBA reduction of endoplasmic reticulum stress in thapsigargin-treated melanoma cell lines. © 2023 by the authors
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The landscape model: a model for exploring trade-offs between agricultural production and the environment
We describe a model framework that simulates spatial and temporal interactions in agricultural landscapes and that can be used to explore trade-offs between production and environment so helping to determine solutions to the problems of sustainable food production. Here we focus on models of agricultural production, water movement and nutrient flow in a landscape. We validate these models against data from two long-term experiments, (the first a continuous wheat experiment and the other a permanent grass-land experiment) and an experiment where water and nutrient flow are measured from isolated catchments. The model simulated wheat yield (RMSE 20.3–28.6%), grain N (RMSE 21.3–42.5%) and P (RMSE 20.2–29% excluding the nil N plots), and total soil organic carbon particularly well (RMSE 3.1 − 13.8 %), the simulations of water flow were also reasonable (RMSE 180.36 and 226.02%). We illustrate the use of our model framework to explore trade-offs between production and nutrient losses
The impact of nitric oxide toxicity on the evolution of the glutathione transferase superfamily: A proposal for an evolutionary driving force
Background: Why do ancestral GSTs utilize cysteine/serine as catalytic residues, whereas more recently evolved GSTs utilize tyrosine? Results: Only the more recently evolved GSTs display enough affinity to bind and make harmless the toxic DNDGIC (a natur
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