Directional translocation resistance of Zika xrRNA

xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, 5 \u2032 and 3 \u2032, are driven through a pore. Pulling the 3 \u2032 end, as done by replicases, elicits a progressive unfolding; pulling the 5 \u2032 end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the 5 \u2032 end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials

Accurate sampling using Langevin dynamics

We show how to derive a simple integrator for the Langevin equation and illustrate how it is possible to check the accuracy of the obtained distribution on the fly, using the concept of effective energy introduced in a recent paper [J. Chem. Phys. 126, 014101 (2007)]. Our integrator leads to correct sampling also in the difficult high-friction limit. We also show how these ideas can be applied in practical simulations, using a Lennard-Jones crystal as a paradigmatic case

Does Ménière's Disease in the Elderly Present Some Peculiar Features?

Object. Aim of our study was to establish some peculiar features of Ménière's Disease (MD) in a group of elderly MD patients, in which the first vertigo spell happened when over 65 years old. Material and Methods. We analyzed a group of 73 younger than 65-years-old and a group of 30 elderly MD patients. All patients underwent a neurotological evaluation, an anamnestic evaluation including a lifetime history of migraine, and blood withdrawal for autoantibody screening. Results. Some differences were found between elderly and younger MD patients. Elderly MD patients presented a higher prevalence of Tumarkin attacks and a lower prevalence of lifetime history of migraine; moreover, they presented a faster develop of hearing loss and vertigo spells than a subgroup of 32 younger patients matched for the duration of illness. Conclusions. Some clinical features of MD in elderly have been pointed out. Particularly, the lower rate of migrainous history and positivity for autoantibodies often associated with MD, in our opinion, support the hypothesis of a vascular disorder acting as a predisposing factor for MD in elderly

Colored-noise thermostats \`a la carte

Recently, we have shown how a colored-noise Langevin equation can be used in the context of molecular dynamics as a tool to obtain dynamical trajectories whose properties are tailored to display desired sampling features. In the present paper, after having reviewed some analytical results for the stochastic differential equations forming the basis of our approach, we describe in detail the implementation of the generalized Langevin equation thermostat and the fitting procedure used to obtain optimal parameters. We discuss in detail the simulation of nuclear quantum effects, and demonstrate that, by carefully choosing parameters, one can successfully model strongly anharmonic solids such as neon. For the reader's convenience, a library of thermostat parameters and some demonstrative code can be downloaded from an on-line repository

Fitting Corrections to an RNA Force Field Using Experimental Data

Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude

Interchain interaction and Davydov splitting in polythiophene crystals: An ab initio approach

The crystal-induced energy splitting of the lowest excitonic state in polymer crystals, the so-called Davydov splitting Δ, is calculated with a first-principles density-matrix scheme. We show that different crystalline arrangements lead to significant variations in Δ, from below to above the thermal energy kBT at room temperature, with relevant implications on the luminescence efficiency. This is one more piece of evidence supporting the fact that control of interchain interactions and solid-state packing is essential for the design of efficient optical devices

Modelling the potential for local management practices to offset climate change impacts on freshwater macroinvertebrate communities

A robust understanding of the interactions between global and local anthropogenic stressors is crucial for ecosystem management in the Anthropocene. Manipulative experiments in the laboratory or in the field can be used to build knowledge about the physiological and ecological effects of stressors, but predicting the combined landscape-scale effects of global stressors such as climate change, and local stressors such as land-use change requires a different approach. Here we used water quality and hydrology process-based models of entire river catchments in combination with a large biomonitoring dataset to predict the responses of macroinvertebrate communities under different climate change and land-use change scenarios. Using the River Thames in the U.K. as a model system, we predicted changes in water quality (temperature, flow, phosphorus [P], nitrogen, dissolved oxygen [DO]) and subsequent changes in macroinvertebrate communities for two climate change scenarios, individually and in combination with intensified agriculture and reduced P pollution (representing improved wastewater treatment). Our models predicted that water-quality changes associated with climate change may not influence total species richness, but that community composition will shift towards more pollution-tolerant and common taxa based on responses of community indices and taxon-specific responses. We also found that the negative impacts of climate change on water quality (e.g., increased P concentration, decreased DO concentration) accumulate through the catchment, but that local land-use practices influencing P dynamics can modify this trend. Furthermore, although the intensified agriculture scenario was predicted to have minimal impacts on macroinvertebrate communities (a result potentially related to shifting baselines as the Thames is already heavily polluted), we found that reduced P pollution resulting from improved wastewater treatment was able to mostly offset the negative impacts of climate change on macroinvertebrate communities. Our results demonstrate that using process-based models to study networks of interacting stressors at a landscape scale can provide useful insights into the ecological impacts of anthropogenic global change, and adds support to the idea that management of local stressors has the potential to mitigate some of the impacts of climate change on ecosystems