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Nucleic Acids: Structures, Properties, and Functions
01 Jan 2000-
TL;DR: In this paper, a comprehensive account of the structures and physical chemistry properties of nucleic acids, with special emphasis on biological function, is provided for those with only a basic understanding of physical chemistry and molecular biology.
Abstract: Providing a comprehensive account of the structures and physical chemistry properties of nucleic acids, with special emphasis on biological function, this text is for those with only a basic understanding of physical chemistry and molecular biology.
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TL;DR: Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens, highlighting the importance of thymically imposed “central” tolerance in controlling autoimmunity.
Abstract: Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue- restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.
2,276 citations
TL;DR: Here, this work reviews DNA strand-displacement-based devices, and looks at how this relatively simple mechanism can lead to a surprising diversity of dynamic behaviour.
Abstract: The programmable and reliable hybridization of DNA strands has enabled the preparation of a wide variety of structures. This Review discusses how, in addition to these static assemblies, the process of displacing — and ultimately replacing — strands also makes possible the construction of dynamic systems such as logic gates or autonomous walkers.
1,520 citations
Cites background from "Nucleic Acids: Structures, Properti..."
...The thermodynamics of DNA hybridization have been carefully characterized within the past few decades [1, 2], allowing the quantitative prediction and design of structures and interactions....
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TL;DR: Six design rules that can be used to deliberately prepare nine distinct colloidal crystal structures, with control over lattice parameters on the 25- to 150-nanometer length scale, represent an advance in synthesizing tailorable macroscale architectures comprising nanoscale materials in a predictable fashion.
Abstract: A current limitation in nanoparticle superlattice engineering is that the identities of the particles being assembled often determine the structures that can be synthesized. Therefore, specific crystallographic symmetries or lattice parameters can only be achieved using specific nanoparticles as building blocks (and vice versa). We present six design rules that can be used to deliberately prepare nine distinct colloidal crystal structures, with control over lattice parameters on the 25- to 150-nanometer length scale. These design rules outline a strategy to independently adjust each of the relevant crystallographic parameters, including particle size (5 to 60 nanometers), periodicity, and interparticle distance. As such, this work represents an advance in synthesizing tailorable macroscale architectures comprising nanoscale materials in a predictable fashion.
944 citations
TL;DR: It is shown that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions.
Abstract: Atomic force microscopes and optical tweezers are widely used to probe the mechanical properties of individual molecules and molecular interactions, by exerting mechanical forces that induce transitions such as unfolding or dissociation. These transitions often occur under nonequilibrium conditions and are associated with hysteresis effects-features usually taken to preclude the extraction of equilibrium information from the experimental data. But fluctuation theorems allow us to relate the work along nonequilibrium trajectories to thermodynamic free-energy differences. They have been shown to be applicable to single-molecule force measurements and have already provided information on the folding free energy of a RNA hairpin. Here we show that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions. We use optical tweezers to measure repeatedly the mechanical work associated with the unfolding and refolding of a small RNA hairpin and an RNA three-helix junction. The resultant work distributions are then analysed according to the theorem and allow us to determine the difference in folding free energy between an RNA molecule and a mutant differing only by one base pair, and the thermodynamic stabilizing effect of magnesium ions on the RNA structure.
938 citations
TL;DR: This work reports the molecular realization, using two-dimensional self-assembly of DNA tiles, of a cellular automaton whose update rule computes the binary function XOR and thus fabricates a fractal pattern—a Sierpinski triangle—as it grows.
Abstract: Algorithms and information, fundamental to technological and biological organization, are also an essential aspect of many elementary physical phenomena, such as molecular self-assembly. Here we report the molecular realization, using two-dimensional self-assembly of DNA tiles, of a cellular automaton whose update rule computes the binary function XOR and thus fabricates a fractal pattern—a Sierpinski triangle—as it grows. To achieve this, abstract tiles were translated into DNA tiles based on double-crossover motifs. Serving as input for the computation, long single-stranded DNA molecules were used to nucleate growth of tiles into algorithmic crystals. For both of two independent molecular realizations, atomic force microscopy revealed recognizable Sierpinski triangles containing 100–200 correct tiles. Error rates during assembly appear to range from 1% to 10%. Although imperfect, the growth of Sierpinski triangles demonstrates all the necessary mechanisms for the molecular implementation of arbitrary cellular automata. This shows that engineered DNA self-assembly can be treated as a Turing-universal biomolecular system, capable of implementing any desired algorithm for computation or construction tasks.
916 citations
Cites methods from "Nucleic Acids: Structures, Properti..."
...For ranges of Gmc and Gse compatible with current experimental conditions, assuming thermodynamic and kinetic parameters extrapolated from the literature of DNA duplex hybridization (Bloomfield et al. 2000), this model (Figure S1) predicts mismatch error rates between 0.1% and 1.0% (Figure 2B)....
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...…by standard methods (Integrated DNA Technologies), PAGE purified, and quantitated by UV absorption at 260 nm in H2O (purified by a Milli-Q system, Millipore, Bedford, Massachusetts, United States) based on extinction coefficients estimated using a nearest-neighbor model (Bloomfield et al. 2000)....
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