Asymptotic structural properties of quasi-random saturated structures of RNA

Background: RNA folding depends on the distribution of kinetic traps in the landscape of all secondary structures. Kinetic traps in the Nussinov energy model are precisely those secondary structures that are saturated, meaning that no base pair can be added without introducing either a pseudoknot or base triple. In previous work, we investigated asymptotic combinatorics of both random saturated structures and of quasi-random saturated structures, where the latter are constructed by a natural stochastic process.Results: We prove that for quasi-random saturated structures with the uniform distribution, the asymptotic expected number of external loops is O(logn) and the asymptotic expected maximum stem length is O(logn), while under the Zipf distribution, the asymptotic expected number of external loops is O(log2n) and the asymptotic expected maximum stem length is O(logn/log logn).Conclusions: Quasi-random saturated structures are generated by a stochastic greedy method, which is simple to implement. Structural features of random saturated structures appear to resemble those of quasi-random saturated structures, and the latter appear to constitute a class for which both the generation of sampled structures as well as a combinatorial investigation of structural features may be simpler to undertake

Without magic bullets: the biological basis for public health interventions against protein folding disorders

Protein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding regulation under a cellular-level cognitive paradigm similar to that proposed by Atlan and Cohen (1998) for the immune system. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of regulatory failure, in essence, a premature aging driven by familiar synergisms between disjunctions of resource allocation and need in the context of socially or physiologically toxic exposures and chronic powerlessness at individual and group scales. Application of an HPA axis model is made to recent observed differences in Alzheimer's onset rates in White and African American subpopulations as a function of an index of distress-proneness

Parsimonious scenario for the emergence of viroid-like replicons de novo

This article belongs to the Special Issue Viroid-2018: International Conference on Viroids and Viroid-Like RNAs.Viroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or several de novo independent evolutionary origins in plants. Here, we discuss the plausibility of de novo emergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluated the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules, e.g., RNA polymerases, RNases, and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.P.C. is supported by a Ramón Areces Foundation Postdoctoral Fellowship. The Spanish Ministerio de Ciencia, Innovación y Universidades-FEDER funds of the European Union support Projects BASIC (PGC2018-098186-B-I00, J.A.C. and P.C.), MiMevo (FIS2017-89773-P, S.M.), and EvolSysVir (BFU2015-65037-P, S.F.E.)

DNA Renaturation at the Water-Phenol Interface

We study DNA adsorption and renaturation in a water-phenol two-phase system, with or without shaking. In very dilute solutions, single-stranded DNA is adsorbed at the interface in a salt-dependent manner. At high salt concentrations the adsorption is irreversible. The adsorption of the single-stranded DNA is specific to phenol and relies on stacking and hydrogen bonding. We establish the interfacial nature of a DNA renaturation at a high salt concentration. In the absence of shaking, this reaction involves an efficient surface diffusion of the single-stranded DNA chains. In the presence of a vigorous shaking, the bimolecular rate of the reaction exceeds the Smoluchowski limit for a three-dimensional diffusion-controlled reaction. DNA renaturation in these conditions is known as the Phenol Emulsion Reassociation Technique or PERT. Our results establish the interfacial nature of PERT. A comparison of this interfacial reaction with other approaches shows that PERT is the most efficient technique and reveals similarities between PERT and the renaturation performed by single-stranded nucleic acid binding proteins. Our results lead to a better understanding of the partitioning of nucleic acids in two-phase systems, and should help design improved extraction procedures for damaged nucleic acids. We present arguments in favor of a role of phenol and water-phenol interface in prebiotic chemistry. The most efficient renaturation reactions (in the presence of condensing agents or with PERT) occur in heterogeneous systems. This reveals the limitations of homogeneous approaches to the biochemistry of nucleic acids. We propose a heterogeneous approach to overcome the limitations of the homogeneous viewpoint

Relating moisture ingress to component strength and stiffness for carbon-fibre composites.

Moisture diffusion studies were performed using unidirectional (UD) tape and quasiisotropic (QI) woven 5-harness satin fabric, carbon fibre reinforced (CFR) epoxy composite materials. Firstly the moisture constants, (i.e. diffusion coefficient, D[x], and equilibrium moisture content, M[max]) were experimentally derived at 70°C and 85% relative humidity (%RH), for the two CFR materials. To investigate moisture absorption as a function of %RH test coupons were conditioned to differing equilibrium moisture levels viz., 70°C/60%RH, 70°C/75%RH, 70°C/85%RH, and 70°C/95%RH. Also oven dry (OD) and as-received (AR) tests were performed for baseline comparison. The effect of moisture absorption on the mechanical behaviour was investigated; lamina properties were studied by measuring tension, compression, shear (inter/intralaminar) strength and stiffness of the UD material. This comprehensive set of testing provided quantitative relationships between moisture content and mechanical properties. The quasi-isotropic lay-up was then utilised to investigate multi-directional laminate lay-ups using open hole tension and compression testing. The experimental data showed that the uptake of moisture in both the materials studied was described well by Fick's Second Law and the properties most affected by moisture ingress were matrix-dominated properties. More specifically, the transverse tensile strength, F[t][2] was most affected by the ingress of moisture, with a near 50% reduction in strength when conditioned to equilibrium moisture content at 70°C/95%RH. Such information is a necessary prerequisite if improved design procedures are going to be developed in the future. The initial phase of testing produced mechanical property/moisture relationships that were employed to predict the strength and stiffness of the material containing specific moisture gradients through-the-thickness (TTT). To be able to predict mechanical properties with different moisture distribution, firstly moisture distribution TTT of the material was modelled using an analytical solution to Fick's Second Law. Then moisture content was considered on a ply-by-ply basis TTT of the laminate; reductions were applied to each individual ply property dependent on the moisture content using the experimentally derived relationships, essentially applying environmental knock-down factors (KEKDF'S) to each individual ply. Classical Laminate Analysis (CLA) was then performed using the Max Stress failure criteria in order to predict the overall laminate failure. A second phase of mechanical testing was then performed to validate these predictions. The mechanical property predictions compared well to the experimental data showing similar reductions in strength for a given profile of moisture in the laminate. The predicted strengths also fell within the measured standard deviation of the experimental data in a significant proportion of the results