191 research outputs found
Anderson Localization, Non-linearity and Stable Genetic Diversity
In many models of genotypic evolution, the vector of genotype populations
satisfies a system of linear ordinary differential equations. This system of
equations models a competition between differential replication rates (fitness)
and mutation. Mutation operates as a generalized diffusion process on genotype
space. In the large time asymptotics, the replication term tends to produce a
single dominant quasispecies, unless the mutation rate is too high, in which
case the populations of different genotypes becomes de-localized. We introduce
a more macroscopic picture of genotypic evolution wherein a random replication
term in the linear model displays features analogous to Anderson localization.
When coupled with non-linearities that limit the population of any given
genotype, we obtain a model whose large time asymptotics display stable
genotypic diversityComment: 25 pages, 8 Figure
Guest charges in an electrolyte: renormalized charge, long- and short-distance behavior of the electric potential and density profile
We complement a recent exact study by L. Samaj on the properties of a guest
charge immersed in a two-dimensional electrolyte with charges . In
particular, we are interested in the behavior of the density profiles and
electric potential created by the charge and the electrolyte, and in the
determination of the renormalized charge which is obtained from the
long-distance asymptotics of the electric potential. In Samaj's previous work,
exact results for arbitrary coulombic coupling were obtained for a
system where all the charges are points, provided and .
Here, we first focus on the mean field situation which we believe describes
correctly the limit but large. In this limit we can
study the case when the guest charge is a hard disk and its charge is above the
collapse value . We compare our results for the renormalized charge
with the exact predictions and we test on a solid ground some conjectures of
the previous study. Our study shows that the exact formulas obtained by Samaj
for the renormalized charge are not valid for , contrary to a
hypothesis put forward by Samaj. We also determine the short-distance
asymptotics of the density profiles of the coions and counterions near the
guest charge, for arbitrary coulombic coupling. We show that the coion density
profile exhibit a change of behavior if the guest charge becomes large enough
(). This is interpreted as a first step of the counterion
condensation (for large coulombic coupling), the second step taking place at
the usual Manning--Oosawa threshold
Field theory for a reaction-diffusion model of quasispecies dynamics
RNA viruses are known to replicate with extremely high mutation rates. These
rates are actually close to the so-called error threshold. This threshold is in
fact a critical point beyond which genetic information is lost through a
second-order phase transition, which has been dubbed the ``error catastrophe.''
Here we explore this phenomenon using a field theory approximation to the
spatially extended Swetina-Schuster quasispecies model [J. Swetina and P.
Schuster, Biophys. Chem. {\bf 16}, 329 (1982)], a single-sharp-peak landscape.
In analogy with standard absorbing-state phase transitions, we develop a
reaction-diffusion model whose discrete rules mimic the Swetina-Schuster model.
The field theory representation of the reaction-diffusion system is
constructed. The proposed field theory belongs to the same universality class
than a conserved reaction-diffusion model previously proposed [F. van Wijland
{\em et al.}, Physica A {\bf 251}, 179 (1998)]. From the field theory, we
obtain the full set of exponents that characterize the critical behavior at the
error threshold. Our results present the error catastrophe from a new point of
view and suggest that spatial degrees of freedom can modify several mean field
predictions previously considered, leading to the definition of characteristic
exponents that could be experimentally measurable.Comment: 13 page
Translocation of structured polynucleotides through nanopores
We investigate theoretically the translocation of structured RNA/DNA
molecules through narrow pores which allow single but not double strands to
pass. The unzipping of basepaired regions within the molecules presents
significant kinetic barriers for the translocation process. We show that this
circumstance may be exploited to determine the full basepairing pattern of
polynucleotides, including RNA pseudoknots. The crucial requirement is that the
translocation dynamics (i.e., the length of the translocated molecular segment)
needs to be recorded as a function of time with a spatial resolution of a few
nucleotides. This could be achieved, for instance, by applying a mechanical
driving force for translocation and recording force-extension curves (FEC's)
with a device such as an atomic force microscope or optical tweezers. Our
analysis suggests that with this added spatial resolution, nanopores could be
transformed into a powerful experimental tool to study the folding of nucleic
acids.Comment: 9 pages, 5 figure
Statistical mechanics of secondary structures formed by random RNA sequences
The formation of secondary structures by a random RNA sequence is studied as
a model system for the sequence-structure problem omnipresent in biopolymers.
Several toy energy models are introduced to allow detailed analytical and
numerical studies. First, a two-replica calculation is performed. By mapping
the two-replica problem to the denaturation of a single homogeneous RNA in
6-dimensional embedding space, we show that sequence disorder is perturbatively
irrelevant, i.e., an RNA molecule with weak sequence disorder is in a molten
phase where many secondary structures with comparable total energy coexist. A
numerical study of various models at high temperature reproduces behaviors
characteristic of the molten phase. On the other hand, a scaling argument based
on the extremal statistics of rare regions can be constructed to show that the
low temperature phase is unstable to sequence disorder. We performed a detailed
numerical study of the low temperature phase using the droplet theory as a
guide, and characterized the statistics of large-scale, low-energy excitations
of the secondary structures from the ground state structure. We find the
excitation energy to grow very slowly (i.e., logarithmically) with the length
scale of the excitation, suggesting the existence of a marginal glass phase.
The transition between the low temperature glass phase and the high temperature
molten phase is also characterized numerically. It is revealed by a change in
the coefficient of the logarithmic excitation energy, from being disorder
dominated to entropy dominated.Comment: 24 pages, 16 figure
Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study
© 2017 Elsevier Ltd Background Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children. Methods In this prospective observational study, we included children and adolescents (age
Red Queen Coevolution on Fitness Landscapes
Species do not merely evolve, they also coevolve with other organisms.
Coevolution is a major force driving interacting species to continuously evolve
ex- ploring their fitness landscapes. Coevolution involves the coupling of
species fit- ness landscapes, linking species genetic changes with their
inter-specific ecological interactions. Here we first introduce the Red Queen
hypothesis of evolution com- menting on some theoretical aspects and empirical
evidences. As an introduction to the fitness landscape concept, we review key
issues on evolution on simple and rugged fitness landscapes. Then we present
key modeling examples of coevolution on different fitness landscapes at
different scales, from RNA viruses to complex ecosystems and macroevolution.Comment: 40 pages, 12 figures. To appear in "Recent Advances in the Theory and
Application of Fitness Landscapes" (H. Richter and A. Engelbrecht, eds.).
Springer Series in Emergence, Complexity, and Computation, 201
Stable stem enabled Shannon entropies distinguish non-coding RNAs from random backgrounds
<p>Abstract</p> <p>Background</p> <p>The computational identification of RNAs in genomic sequences requires the identification of signals of RNA sequences. Shannon base pairing entropy is an indicator for RNA secondary structure fold certainty in detection of structural, non-coding RNAs (ncRNAs). Under the Boltzmann ensemble of secondary structures, the probability of a base pair is estimated from its frequency across all the alternative equilibrium structures. However, such an entropy has yet to deliver the desired performance for distinguishing ncRNAs from random sequences. Developing novel methods to improve the entropy measure performance may result in more effective ncRNA gene finding based on structure detection.</p> <p>Results</p> <p>This paper shows that the measuring performance of base pairing entropy can be significantly improved with a constrained secondary structure ensemble in which only canonical base pairs are assumed to occur in energetically stable stems in a fold. This constraint actually reduces the space of the secondary structure and may lower the probabilities of base pairs unfavorable to the native fold. Indeed, base pairing entropies computed with this constrained model demonstrate substantially narrowed gaps of Z-scores between ncRNAs, as well as drastic increases in the Z-score for all 13 tested ncRNA sets, compared to shuffled sequences.</p> <p>Conclusions</p> <p>These results suggest the viability of developing effective structure-based ncRNA gene finding methods by investigating secondary structure ensembles of ncRNAs.</p
Analysis of conserved microRNAs in floral tissues of sexual and apomictic Boechera species
<p>Abstract</p> <p>Background</p> <p>Apomixis or asexual seed formation represents a potentially important agronomic trait whose introduction into crop plants could be an effective way to fix and perpetuate a desirable genotype through successive seed generations. However, the gene regulatory pathways underlying apomixis remain unknown. In particular, the potential function of microRNAs, which are known to play crucial roles in many aspects of plant growth and development, remains to be determined with regards to the switch from sexual to apomictic reproduction.</p> <p>Results</p> <p>Using bioinformatics and microarray validation procedures, 51 miRNA families conserved among angiosperms were identified in <it>Boechera</it>. Microarray assay confirmed 15 of the miRNA families that were identified by bioinformatics techniques. 30 cDNA sequences representing 26 miRNAs could fold back into stable pre-miRNAs. 19 of these pre-miRNAs had miRNAs with <it>Boechera</it>-specific nucleotide substitutions (NSs). Analysis of the Gibbs free energy (ΔG) of these pre-miRNA stem-loops with NSs showed that the <it>Boechera</it>-specific miRNA NSs significantly (p ≤ 0.05) enhance the stability of stem-loops. Furthermore, six transcription factors, the Squamosa promoter binding protein like SPL6, SPL11 and SPL15, Myb domain protein 120 (MYB120), RELATED TO AP2.7 DNA binding (RAP2.7, TOE1 RAP2.7) and TCP family transcription factor 10 (TCP10) were found to be expressed in sexual or apomictic ovules. However, only SPL11 showed differential expression with significant (p ≤ 0.05) up-regulation at the megaspore mother cell (MMC) stage of ovule development in apomictic genotypes.</p> <p>Conclusions</p> <p>This study constitutes the first extensive insight into the conservation and expression of microRNAs in <it>Boechera </it>sexual and apomictic species. The miR156/157 target squamosa promoter binding protein-like 11 (SPL11) was found differentially expressed with significant (p ≤ 0.05) up-regulation at the MMC stage of ovule development in apomictic genotypes. The results also demonstrate that nucleotide changes in mature miRNAs significantly (p ≤ 0.05) enhance the thermodynamic stability of pre-miRNA stem-loops.</p
Hybridization thermodynamics of NimbleGen Microarrays
Background
While microarrays are the predominant method for gene expression profiling, probe signal variation is still an area of active research. Probe signal is sequence dependent and affected by probe-target binding strength and the competing formation of probe-probe dimers and secondary structures in probes and targets.
Results
We demonstrate the benefits of an improved model for microarray hybridization and assess the relative contributions of the probe-target binding strength and the different competing structures. Remarkably, specific and unspecific hybridization were apparently driven by different energetic contributions: For unspecific hybridization, the melting temperature Tm was the best predictor of signal variation. For specific hybridization, however, the effective interaction energy that fully considered competing structures was twice as powerful a predictor of probe signal variation. We show that this was largely due to the effects of secondary structures in the probe and target molecules. The predictive power of the strength of these intramolecular structures was already comparable to that of the melting temperature or the free energy of the probe-target duplex.
Conclusions
This analysis illustrates the importance of considering both the effects of probe-target binding strength and the different competing structures. For specific hybridization, the secondary structures of probe and target molecules turn out to be at least as important as the probe-target binding strength for an understanding of the observed microarray signal intensities. Besides their relevance for the design of new arrays, our results demonstrate the value of improving thermodynamic models for the read-out and interpretation of microarray signals
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