30,944 research outputs found
Diffusion, dimensionality and noise in transcriptional regulation
The precision of biochemical signaling is limited by randomness in the
diffusive arrival of molecules at their targets. For proteins binding to the
specific sites on the DNA and regulating transcription, the ability of the
proteins to diffuse in one dimension by sliding along the length of the DNA, in
addition to their diffusion in bulk solution, would seem to generate a larger
target for DNA binding, consequently reducing the noise in the occupancy of the
regulatory site. Here we show that this effect is largely cancelled by the
enhanced temporal correlations in one dimensional diffusion. With realistic
parameters, sliding along DNA has surprisingly little effect on the physical
limits to the precision of transcriptional regulation.Comment: 8 pages, 2 figure
DNA Authentication of St John’s Wort (Hypericum perforatum L.) Commercial Products Targeting the ITS Region
open access articleThere is considerable potential for the use of DNA barcoding methods to authenticate raw medicinal plant materials, but their application to testing commercial products has been controversial. A simple PCR test targeting species-specific sequences within the nuclear ribosomal internal transcribed spacer (ITS) region was adapted to screen commercial products for the presence of Hypericum perforatum L. material. DNA differing widely in amount and extent of fragmentation was detected in a number of product types. Two assays were designed to further analyse this DNA using a curated database of selected Hypericum ITS sequences: A qPCR assay based on a species-specific primer pair spanning the ITS1 and ITS2 regions, using synthetic DNA reference standards for DNA quantitation and a Next Generation Sequencing (NGS) assay separately targeting the ITS1 and ITS2 regions. The ability of the assays to detect H. perforatum DNA sequences in processed medicines was investigated. Out of twenty different matrices tested, both assays detected H. perforatum DNA in five samples with more than 103 ITS copies µL−1 DNA extract, whilst the qPCR assay was also able to detect lower levels of DNA in two further samples. The NGS assay confirmed that H. perforatum was the major species in all five positive samples, though trace contaminants were also detected
How crystals that sense and respond to their environments could evolve
An enduring mystery in biology is how a physical entity simple enough to have arisen spontaneously could have evolved into the complex life seen on Earth today. Cairns-Smith has proposed that life might have originated in clays which stored genomes consisting of an arrangement of crystal monomers that was replicated during growth. While a clay genome is simple enough to have conceivably arisen spontaneously, it is not obvious how it might have produced more complex forms as a result of evolution. Here, we examine this possibility in the tile assembly model, a generalized model of crystal growth that has been used to study the self-assembly of DNA tiles. We describe hypothetical crystals for which evolution of complex crystal sequences is driven by the scarceness of resources required for growth. We show how, under certain circumstances, crystal growth that performs computation can predict which resources are abundant. In such cases, crystals executing programs that make these predictions most accurately will grow fastest. Since crystals can perform universal computation, the complexity of computation that can be used to optimize growth is unbounded. To the extent that lessons derived from the tile assembly model might be applicable to mineral crystals, our results suggest that resource scarcity could conceivably have provided the evolutionary pressures necessary to produce complex clay genomes that sense and respond to changes in their environment
Experimental Progress in Computation by Self-Assembly of DNA Tilings
Approaches to DNA-based computing by self-assembly require the
use of D. T A nanostructures, called tiles, that have efficient chemistries, expressive
computational power: and convenient input and output (I/O) mechanisms.
We have designed two new classes of DNA tiles: TAO and TAE, both
of which contain three double-helices linked by strand exchange. Structural
analysis of a TAO molecule has shown that the molecule assembles efficiently
from its four component strands. Here we demonstrate a novel method for
I/O whereby multiple tiles assemble around a single-stranded (input) scaffold
strand. Computation by tiling theoretically results in the formation of structures
that contain single-stranded (output) reported strands, which can then
be isolated for subsequent steps of computation if necessary. We illustrate the
advantages of TAO and TAE designs by detailing two examples of massively
parallel arithmetic: construction of complete XOR and addition tables by linear
assemblies of DNA tiles. The three helix structures provide flexibility for
topological routing of strands in the computation: allowing the implementation
of string tile models
DNA Computing by Self-Assembly
Information and algorithms appear to be central to biological organization
and processes, from the storage and reproduction of genetic information to
the control of developmental processes to the sophisticated computations
performed by the nervous system. Much as human technology uses electronic
microprocessors to control electromechanical devices, biological
organisms use biochemical circuits to control molecular and chemical events.
The engineering and programming of biochemical circuits, in vivo and in
vitro, would transform industries that use chemical and nanostructured
materials. Although the construction of biochemical circuits has been
explored theoretically since the birth of molecular biology, our practical
experience with the capabilities and possible programming of biochemical
algorithms is still very young
Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking
Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di-guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling
A multiscale model for collagen alignment in wound healing
It is thought that collagen alignment plays a significant part in scar tissue formation during dermal wound healing. We present a multiscale model for collagen deposition and alignment during this process. We consider fibroblasts as discrete units moving within an extracellular matrix of collagen and fibrin modelled as continua. Our model includes flux induced alignment of collagen by fibroblasts, and contact guidance of fibroblasts by collagen fibres. We can use the model to predict the effects of certain manipulations, such as varying fibroblast speed, or placing an aligned piece of tissue in the wound. We also simulate experiments which alter the TGF-β concentrations in a healing dermal wound and use the model to offer an explanation of the observed influence of this growth factor on scarring
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